Humira

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ANNEX I 

 
SUMMARY OF PRODUCT CHARACTERISTICS 

 



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1. NAME OF THE MEDICINAL PRODUCT  
 
Humira 20 mg solution for injection in pre-filled syringe  
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION  
 
Each 0.2 ml single dose pre-filled syringe contains 20 mg of adalimumab.  
 
Adalimumab is a recombinant human monoclonal antibody produced in Chinese Hamster Ovary cells. 
 
For the full list of excipients, see section 6.1.  
 
 
3. PHARMACEUTICAL FORM  
 
Solution for injection. (injection) 
 
Clear, colourless solution.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications  
 
Juvenile idiopathic arthritis 
 
Polyarticular juvenile idiopathic arthritis 
 
Humira in combination with methotrexate is indicated for the treatment of active polyarticular juvenile 
idiopathic arthritis, in patients from the age of 2 years who have had an inadequate response to one or 
more disease-modifying anti-rheumatic drugs (DMARDs). Humira can be given as monotherapy in case 
of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate (for the 
efficacy in monotherapy see section 5.1). Humira has not been studied in patients aged less than 2 years. 
 
Enthesitis-related arthritis 
 
Humira is indicated for the treatment of active enthesitis-related arthritis in patients, 6 years of age and 
older, who have had an inadequate response to, or who are intolerant of, conventional therapy (see section 
5.1). 
 
Paediatric plaque psoriasis 
 
Humira is indicated for the treatment of severe chronic plaque psoriasis in children and adolescents from 
4 years of age who have had an inadequate response to or are inappropriate candidates for topical therapy 
and phototherapies. 
 
Paediatric Crohn's disease  
 
Humira is indicated for the treatment of moderately to severely active Crohn's disease in paediatric 
patients (from 6 years of age) who have had an inadequate response to conventional therapy including 
primary nutrition therapy and a corticosteroid and/or an immunomodulator, or who are intolerant to or 
have contraindications for such therapies. 



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Paediatric Uveitis 
 
Humira is indicated for the treatment of paediatric chronic non-infectious anterior uveitis in patients from 
2 years of age who have had an inadequate response to or are intolerant to conventional therapy, or in 
whom conventional therapy is inappropriate. 
 
4.2 Posology and method of administration   
 
Humira treatment should be initiated and supervised by specialist physicians experienced in the diagnosis 
and treatment of conditions for which Humira is indicated. Ophthalmologists are advised to consult with 
an appropriate specialist before initiation of treatment with Humira (see section 4.4). Patients treated with 
Humira should be given the Patient Reminder Card. 
 
After proper training in injection technique, patients may self-inject with Humira if their physician 
determines that it is appropriate and with medical follow-up as necessary.  
 
During treatment with Humira, other concomitant therapies (e.g., corticosteroids and/or 
immunomodulatory agents) should be optimised. 
 
Posology 
 
Paediatric population 
 
Juvenile idiopathic arthritis 
 
Polyarticular juvenile idiopathic arthritis from 2 years of age 
 
The recommended dose of Humira for patients with polyarticular juvenile idiopathic arthritis from 2 years 
of age is based on body weight (Table 1). Humira is administered every other week via subcutaneous 
injection. 
 

Table 1. Humira Dose for Patients with Polyarticular Juvenile Idiopathic Arthritis  
 

Patient Weight Dosing Regimen 

10 kg to < 30 kg 20 mg every other week 

≥ 30 kg 40 mg every other week 
 
Available data suggest that clinical response is usually achieved within 12 weeks of treatment. Continued 
therapy should be carefully reconsidered in a patient not responding within this time period. 
 
There is no relevant use of Humira in patients aged less than 2 years for this indication. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Enthesitis-related arthritis 
 
The recommended dose of Humira for patients with enthesitis-related arthritis from 6 years of age is based 
on body weight (Table 2). Humira is administered every other week via subcutaneous injection.  
 



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Table 2. Humira Dose for Patients with Enthesitis-Related Arthritis  
 

Patient Weight Dosing Regimen 

15 kg to < 30 kg 20 mg every other week 

≥ 30 kg 40 mg every other week 
 
Humira has not been studied in patients with enthesitis-related arthritis aged less than 6 years. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Paediatric plaque psoriasis 
 
The recommended Humira dose for patients with plaque psoriasis from 4 to 17 years of age is based on 
body weight (Table 3). Humira is administered via subcutaneous injection. 
 

Table 3. Humira Dose for Paediatric Patients with Plaque Psoriasis  
 

Patient Weight Dosing Regimen 

15 kg to < 30 kg Initial dose of 20 mg, followed by 
20 mg given every other week 

starting one week after the initial 
dose 

≥ 30 kg Initial dose of 40 mg, followed by 
40 mg given every other week 

starting one week after the initial 
dose 

 
Continued therapy beyond 16 weeks should be carefully considered in a patient not responding within this 
time period. 
 
If retreatment with Humira is indicated, the above guidance on dose and treatment duration should be 
followed. 
 
The safety of Humira in paediatric patients with plaque psoriasis has been assessed for a mean of 
13 months. 
 
There is no relevant use of Humira in children aged less than 4 years for this indication. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Paediatric Crohn's disease 
 
The recommended dose of Humira for patients with Crohn’s disease from 6 to 17 years of age is based on 
body weight (Table 4). Humira is administered via subcutaneous injection. 



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Table 4. Humira Dose for Paediatric Patients with Crohn’s disease 

 
Patient 
Weight 

Induction Dose Maintenance 
Dose 

Starting at 
Week 4

< 40 kg  40 mg at week 0 and 20 mg at week 2 
 

In case there is a need for a more rapid response to therapy with the 
awareness that the risk for adverse events may be higher with use of the 
higher induction dose, the following dose may be used: 
 80 mg at week 0 and 40 mg at week 2

20 mg every 
other week 

≥ 40 kg  80 mg at week 0 and 40 mg at week 2 
 

In case there is a need for a more rapid response to therapy with the 
awareness that the risk for adverse events may be higher with use of the 
higher induction dose, the following dose may be used: 
 160 mg at week 0 and 80 mg at week 2

40 mg every 
other week 

 
Patients who experience insufficient response may benefit from an increase in dosage: 
 < 40 kg: 20 mg every week 
 ≥ 40 kg: 40 mg every week or 80 mg every other week 
 
Continued therapy should be carefully considered in a subject not responding by week 12. 
 
There is no relevant use of Humira in children aged less than 6 years for this indication. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Paediatric Uveitis 
 
The recommended dose of Humira for paediatric patients with uveitis from 2 years of age is based on 
body weight (Table 5). Humira is administered via subcutaneous injection. 
 
In paediatric uveitis, there is no experience in the treatment with Humira without concomitant treatment 
with methotrexate. 
 

Table 5. Humira Dose for Paediatric Patients with Uveitis 
 

Patient Weight Dosing Regimen 

< 30 kg 20 mg every other week in 
combination with methotrexate 

≥ 30 kg 40 mg every other week in 
combination with methotrexate 

 
When Humira therapy is initiated, a loading dose of 40 mg for patients < 30 kg or 80 mg for patients 
≥ 30 kg may be administered one week prior to the start of maintenance therapy. No clinical data are 
available on the use of a Humira loading dose in children < 6 years of age (see section 5.2). 
 



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There is no relevant use of Humira in children aged less than 2 years in this indication. 
 
It is recommended that the benefit and risk of continued long-term treatment should be evaluated on a 
yearly basis (see section 5.1). 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Renal and/or hepatic impairment 
 
Humira has not been studied in these patient populations. No dose recommendations can be made. 
 
Method of administration 
 
Humira is administered by subcutaneous injection. Full instructions for use are provided in the package 
leaflet. 
 
Humira is available in other strengths and presentations. 
 
4.3 Contraindications  
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  
 
Active tuberculosis or other severe infections such as sepsis and opportunistic infections (see section 4.4). 
 
Moderate to severe heart failure (NYHA class III/IV) (see section 4.4). 
 
4.4 Special warnings and precautions for use 
 
Traceability 
 
In order to improve traceability of biological medicinal products, the name and the batch number of the 
administered product should be clearly recorded. 
 
Infections 
 
Patients taking TNF -antagonists are more susceptible to serious infections. Impaired lung function may 
increase the risk for developing infections. Patients must therefore be monitored closely for infections, 
including tuberculosis, before, during and after treatment with Humira. Because the elimination of 
adalimumab may take up to four months, monitoring should be continued throughout this period. 
 
Treatment with Humira should not be initiated in patients with active infections including chronic or 
localised infections until infections are controlled. In patients who have been exposed to tuberculosis and 
patients who have travelled in areas of high risk of tuberculosis or endemic mycoses, such as 
histoplasmosis, coccidioidomycosis, or blastomycosis, the risk and benefits of treatment with Humira 
should be considered prior to initiating therapy (see Other opportunistic infections). 
 
Patients who develop a new infection while undergoing treatment with Humira should be monitored 
closely and undergo a complete diagnostic evaluation. Administration of Humira should be discontinued if 
a patient develops a new serious infection or sepsis and appropriate antimicrobial or antifungal therapy 
should be initiated until the infection is controlled. Physicians should exercise caution when considering 
the use of Humira in patients with a history of recurring infection or with underlying conditions which 
may predispose patients to infections, including the use of concomitant immunosuppressive medications. 



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Serious infections 
 
Serious infections, including sepsis, due to bacterial, mycobacterial, invasive fungal, parasitic, viral, or 
other opportunistic infections such as listeriosis, legionellosis and pneumocystis have been reported in 
patients receiving Humira.   
 
Other serious infections seen in clinical trials include pneumonia, pyelonephritis, septic arthritis and 
septicaemia. Hospitalisation or fatal outcomes associated with infections have been reported.  
 
Tuberculosis 
 
Tuberculosis, including reactivation and new onset of tuberculosis, has been reported in patients receiving 
Humira. Reports included cases of pulmonary and extra-pulmonary (i.e. disseminated) tuberculosis.  
 
Before initiation of therapy with Humira, all patients must be evaluated for both active or inactive 
(“latent”) tuberculosis infection. This evaluation should include a detailed medical assessment of patient 
history of tuberculosis or possible previous exposure to people with active tuberculosis and previous 
and/or current immunosuppressive therapy. Appropriate screening tests (i.e. tuberculin skin test and chest 
X-ray) should be performed in all patients (local recommendations may apply). It is recommended that the 
conduct and results of these tests are recorded in the Patient Reminder Card. Prescribers are reminded of 
the risk of false negative tuberculin skin test results, especially in patients who are severely ill or 
immunocompromised.  
 
If active tuberculosis is diagnosed, Humira therapy must not be initiated (see section 4.3).  
 
In all situations described below, the benefit/risk balance of therapy should be very carefully considered. 
 
If latent tuberculosis is suspected, a physician with expertise in the treatment of tuberculosis should be 
consulted.  
 
If latent tuberculosis is diagnosed, appropriate treatment must be started with anti-tuberculosis prophylaxis 
treatment before the initiation of Humira and in accordance with local recommendations.  
 
Use of anti-tuberculosis prophylaxis treatment should also be considered before the initiation of Humira in 
patients with several or significant risk factors for tuberculosis despite a negative test for tuberculosis and 
in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment 
cannot be confirmed.   
 
Despite prophylactic treatment for tuberculosis, cases of reactivated tuberculosis have occurred in patients 
treated with Humira. Some patients who have been successfully treated for active tuberculosis have 
redeveloped tuberculosis while being treated with Humira. 
 
Patients should be instructed to seek medical advice if signs/symptoms suggestive of a tuberculosis 
infection (e.g., persistent cough, wasting/weight loss, low grade fever, listlessness) occur during or after 
therapy with Humira.  
 
Other opportunistic infections 
 
Opportunistic infections, including invasive fungal infections have been observed in patients receiving 
Humira. These infections have not consistently been recognised in patients taking TNF-antagonists and 
this has resulted in delays in appropriate treatment, sometimes resulting in fatal outcomes.  
 



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For patients who develop the signs and symptoms such as fever, malaise, weight loss, sweats, cough, 
dyspnoea, and/or pulmonary infiltrates or other serious systemic illness with or without concomitant shock 
an invasive fungal infection should be suspected and administration of Humira should be promptly 
discontinued. Diagnosis and administration of empiric antifungal therapy in these patients should be made 
in consultation with a physician with expertise in the care of patients with invasive fungal infections.  
 
Hepatitis B reactivation 
 
Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including Humira, who are 
chronic carriers of this virus (i.e. surface antigen positive). Some cases have had a fatal outcome. Patients 
should be tested for HBV infection before initiating treatment with Humira. For patients who test positive 
for hepatitis B infection, consultation with a physician with expertise in the treatment of hepatitis B is 
recommended. 
 
Carriers of HBV who require treatment with Humira should be closely monitored for signs and symptoms 
of active HBV infection throughout therapy and for several months following termination of therapy. 
Adequate data from treating patients who are carriers of HBV with anti-viral therapy in conjunction with 
TNF-antagonist therapy to prevent HBV reactivation are not available. In patients who develop HBV 
reactivation, Humira should be stopped and effective anti-viral therapy with appropriate supportive 
treatment should be initiated.  
 
Neurological events  
 
TNF-antagonists including Humira have been associated in rare instances with new onset or exacerbation 
of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease 
including multiple sclerosis and optic neuritis, and peripheral demyelinating disease, including Guillain-
Barré syndrome. Prescribers should exercise caution in considering the use of Humira in patients with pre-
existing or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of 
Humira should be considered if any of these disorders develop. There is a known association between 
intermediate uveitis and central demyelinating disorders. Neurologic evaluation should be performed in 
patients with non-infectious intermediate uveitis prior to the initiation of Humira therapy and regularly 
during treatment to assess for pre-existing or developing central demyelinating disorders.  
 
Allergic reactions 
 
Serious allergic reactions associated with Humira were rare during clinical trials. Non-serious allergic 
reactions associated with Humira were uncommon during clinical trials. Reports of serious allergic 
reactions including anaphylaxis have been received following Humira administration. If an anaphylactic 
reaction or other serious allergic reaction occurs, administration of Humira should be discontinued 
immediately and appropriate therapy initiated.  
 
Immunosuppression 
 
In a study of 64 patients with rheumatoid arthritis that were treated with Humira, there was no evidence of 
depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or change in 
enumeration of effector T-, B-, NK-cells, monocyte/macrophages, and neutrophils. 
 
Malignancies and lymphoproliferative disorders 
 
In the controlled portions of clinical trials of TNF-antagonists, more cases of malignancies including 
lymphoma have been observed among patients receiving a TNF-antagonist compared with control 
patients. However, the occurrence was rare. In the post marketing setting, cases of leukaemia have been 
reported in patients treated with a TNF-antagonist. There is an increased background risk for lymphoma 



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and leukaemia in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, 
which complicates the risk estimation. With the current knowledge, a possible risk for the development of 
lymphomas, leukaemia, and other malignancies in patients treated with a TNF-antagonist cannot be 
excluded. 
 
Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 
22 years of age) treated with TNF-antagonists (initiation of therapy ≤ 18 years of age), including 
adalimumab in the post marketing setting. Approximately half the cases were lymphomas. The other cases 
represented a variety of different malignancies and included rare malignancies usually associated with 
immunosuppression. A risk for the development of malignancies in children and adolescents treated with 
TNF-antagonists cannot be excluded.  
 
Rare postmarketing cases of hepatosplenic T-cell lymphoma have been identified in patients treated with 
adalimumab. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. 
Some of these hepatosplenic T-cell lymphomas with Humira have occurred in young adult patients on 
concomitant treatment with azathioprine or 6-mercaptopurine used for inflammatory bowel disease. The 
potential risk with the combination of azathioprine or 6-mercaptopurine and Humira should be carefully 
considered. A risk for the development of hepatosplenic T-cell lymphoma in patients treated with Humira 
cannot be excluded (see section 4.8). 
 
No studies have been conducted that include patients with a history of malignancy or in whom treatment 
with Humira is continued following development of malignancy. Thus, additional caution should be 
exercised in considering Humira treatment of these patients (see section 4.8). 
 
All patients, and in particular patients with a medical history of extensive immunosuppressant therapy or 
psoriasis patients with a history of PUVA treatment should be examined for the presence of non-
melanoma skin cancer prior to and during treatment with Humira. Melanoma and Merkel cell carcinoma 
have also been reported in patients treated with TNF-antagonists including adalimumab (see section 4.8). 
 
In an exploratory clinical trial evaluating the use of another TNF-antagonist, infliximab, in patients with 
moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, mostly in the lung 
or head and neck, were reported in infliximab-treated patients compared with control patients. All patients 
had a history of heavy smoking. Therefore, caution should be exercised when using any TNF-antagonist in 
COPD patients, as well as in patients with increased risk for malignancy due to heavy smoking. 
 
With current data it is not known if adalimumab treatment influences the risk for developing dysplasia or 
colon cancer. All patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma 
(for example, patients with long-standing ulcerative colitis or primary sclerosing cholangitis), or who had 
a prior history of dysplasia or colon carcinoma should be screened for dysplasia at regular intervals before 
therapy and throughout their disease course. This evaluation should include colonoscopy and biopsies per 
local recommendations. 
 
Haematologic reactions 
 
Rare reports of pancytopenia including aplastic anaemia have been reported with TNF-antagonists.  
Adverse events of the haematologic system, including medically significant cytopenia (e.g. 
thrombocytopenia, leukopenia) have been reported with Humira. All patients should be advised to seek 
immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias (e.g. 
persistent fever, bruising, bleeding, pallor) while on Humira. Discontinuation of Humira therapy should be 
considered in patients with confirmed significant haematologic abnormalities. 
 



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Vaccinations  
 
Similar antibody responses to the standard 23-valent pneumococcal vaccine and the influenza trivalent 
virus vaccination were observed in a study in 226 adult subjects with rheumatoid arthritis who were 
treated with adalimumab or placebo. No data are available on the secondary transmission of infection by 
live vaccines in patients receiving Humira.   
 
It is recommended that paediatric patients, if possible, be brought up to date with all immunisations in 
agreement with current immunisation guidelines prior to initiating Humira therapy. 
 
Patients on Humira may receive concurrent vaccinations, except for live vaccines. Administration of live 
vaccines (e.g., BCG vaccine) to infants exposed to adalimumab in utero is not recommended for 5 months 
following the mother’s last adalimumab injection during pregnancy. 
 
Congestive heart failure 
 
In a clinical trial with another TNF-antagonist worsening congestive heart failure and increased mortality 
due to congestive heart failure have been observed. Cases of worsening congestive heart failure have also 
been reported in patients receiving Humira. Humira should be used with caution in patients with mild 
heart failure (NYHA class I/II). Humira is contraindicated in moderate to severe heart failure (see section 
4.3). Treatment with Humira must be discontinued in patients who develop new or worsening symptoms 
of congestive heart failure. 
 
Autoimmune processes 
 
Treatment with Humira may result in the formation of autoimmune antibodies. The impact of long-term 
treatment with Humira on the development of autoimmune diseases is unknown. If a patient develops 
symptoms suggestive of a lupus-like syndrome following treatment with Humira and is positive for 
antibodies against double-stranded DNA, further treatment with Humira should not be given (see section 
4.8). 
 
Concurrent administration of biologic DMARDS or TNF-antagonists 
 
Serious infections were seen in clinical studies with concurrent use of anakinra and another 
TNF-antagonist, etanercept, with no added clinical benefit compared to etanercept alone. Because of the 
nature of the adverse events seen with the combination of etanercept and anakinra therapy, similar 
toxicities may also result from the combination of anakinra and other TNF-antagonists. Therefore, the 
combination of adalimumab and anakinra is not recommended. (See section 4.5). 
 
Concomitant administration of adalimumab with other biologic DMARDS (e.g, anakinra and abatacept) or 
other TNF-antagonists is not recommended based upon the possible increased risk for infections, 
including serious infections and other potential pharmacological interactions. (See section 4.5). 
 
Surgery 
 
There is limited safety experience of surgical procedures in patients treated with Humira. The long half-
life of adalimumab should be taken into consideration if a surgical procedure is planned. A patient who 
requires surgery while on Humira should be closely monitored for infections, and appropriate actions 
should be taken. There is limited safety experience in patients undergoing arthroplasty while receiving 
Humira.  
 



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Small bowel obstruction 
 
Failure to respond to treatment for Crohn’s disease may indicate the presence of fixed fibrotic stricture 
that may require surgical treatment. Available data suggest that Humira does not worsen or cause 
strictures. 
 
Elderly 
 
The frequency of serious infections among Humira treated subjects over 65 years of age (3.7%) was 
higher than for those under 65 years of age (1.5%). Some of those had a fatal outcome. Particular attention 
regarding the risk for infection should be paid when treating the elderly. 
 
Paediatric population 
 
See Vaccinations above. 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
Humira has been studied in rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and psoriatic 
arthritis patients taking Humira as monotherapy and those taking concomitant methotrexate. Antibody 
formation was lower when Humira was given together with methotrexate in comparison with use as 
monotherapy. Administration of Humira without methotrexate resulted in increased formation of 
antibodies, increased clearance and reduced efficacy of adalimumab (see section 5.1).  
 
The combination of Humira and anakinra is not recommended (see section 4.4 “Concurrent administration 
of biologic DMARDS or TNF-antagonists”).  
 
The combination of Humira and abatacept is not recommended (see section 4.4 “Concurrent 
administration of biologic DMARDS or TNF-antagonists”). 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential 
 
Women of childbearing potential should consider the use of adequate contraception to prevent pregnancy 
and continue its use for at least five months after the last Humira treatment. 
 
Pregnancy 
 
A large number (approximately 2100) of prospectively collected pregnancies exposed to adalimumab 
resulting in live birth with known outcomes, including more than 1500 exposed during the first trimester, 
does not indicate an increase in the rate of malformation in the newborn. 
 
In a prospective cohort registry, 257 women with rheumatoid arthritis (RA) or Crohn’s disease (CD) 
treated with adalimumab at least during the first trimester and 120 women with RA or CD not treated with 
adalimumab were enrolled.  The primary endpoint was the birth prevalence of major birth defects. The 
rate of pregnancies ending with at least one live born infant with a major birth defect was 6/69 (8.7%) in 
the adalimumab-treated women with RA and 5/74 (6.8%) in the untreated women with RA (unadjusted 
OR 1.31, 95% CI 0.38-4.52) and 16/152 (10.5%) in the adalimumab-treated women with CD and 3/32 
(9.4%) in the untreated women with CD (unadjusted OR 1.14, 95% CI 0.31-4.16). The adjusted OR 
(accounting for baseline differences) was 1.10 (95% CI 0.45-2.73) with RA and CD combined. There were 
no distinct differences between adalimumab-treated and untreated women for the secondary endpoints 
spontaneous abortions, minor birth defects, preterm delivery, birth size and serious or opportunistic 



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infections and no stillbirths or malignancies were reported. The interpretation of data may be impacted due 
to methodological limitations of the study, including small sample size and non-randomized design. 
 
In a developmental toxicity study conducted in monkeys, there was no indication of maternal toxicity, 
embryotoxicity or teratogenicity. Preclinical data on postnatal toxicity of adalimumab are not available 
(see section 5.3). 
 
Due to its inhibition of TNF, adalimumab administered during pregnancy could affect normal immune 
responses in the newborn.  Adalimumab should only be used during pregnancy if clearly needed. 
 
Adalimumab may cross the placenta into the serum of infants born to women treated with adalimumab 
during pregnancy. Consequently, these infants may be at increased risk for infection. Administration of 
live vaccines (e.g., BCG vaccine) to infants exposed to adalimumab in utero is not recommended for 
5 months following the mother’s last adalimumab injection during pregnancy. 
 
Breast-feeding 
 
Limited information from the published literature indicates that adalimumab is excreted in breast milk at 
very low concentrations with the presence of adalimumab in human milk at concentrations of 0.1% to 1% 
of the maternal serum level. Given orally, immunoglobulin G proteins undergo intestinal proteolysis and 
have poor bioavailability. No effects on the breastfed newborns/infants are anticipated. Consequently, 
Humira can be used during breastfeeding. 
 
Fertility 
 
Preclinical data on fertility effects of adalimumab are not available. 
 
4.7 Effects on ability to drive and use machines  
 
Humira may have a minor influence on the ability to drive and use machines. Vertigo and visual 
impairment may occur following administration of Humira (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Humira was studied in 9,506 patients in pivotal controlled and open label trials for up to 60 months or 
more. These trials included rheumatoid arthritis patients with short term and long standing disease, 
juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis) as 
well as axial spondyloarthritis (ankylosing spondylitis and axial spondyloarthritis without radiographic 
evidence of AS), psoriatic arthritis, Crohn’s disease, ulcerative colitis, psoriasis, hidradenitis suppurativa 
and uveitis patients. The pivotal controlled studies involved 6,089 patients receiving Humira and 3,801 
patients receiving placebo or active comparator during the controlled period. 
 
The proportion of patients who discontinued treatment due to adverse events during the double-blind, 
controlled portion of pivotal studies was 5.9% for patients taking Humira and 5.4% for control treated 
patients. 
 
The most commonly reported adverse reactions are infections (such as nasopharyngitis, upper respiratory 
tract infection and sinusitis), injection site reactions (erythema, itching, haemorrhage, pain or swelling), 
headache and musculoskeletal pain. 
 



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Serious adverse reactions have been reported for Humira. TNF-antagonists, such as Humira affect the 
immune system and their use may affect the body’s defence against infection and cancer. 
Fatal and life-threatening infections (including sepsis, opportunistic infections and TB), HBV reactivation 
and various malignancies (including leukaemia, lymphoma and HSTCL) have also been reported with use 
of Humira. 
 
Serious haematological, neurological and autoimmune reactions have also been reported. These include 
rare reports of pancytopenia, aplastic anaemia, central and peripheral demyelinating events and reports of 
lupus, lupus-related conditions and Stevens-Johnson syndrome. 
 
Paediatric population 
 
In general, the adverse events in paediatric patients were similar in frequency and type to those seen in 
adult patients. 
 
Tabulated list of adverse reactions 
 
The following list of adverse reactions is based on experience from clinical trials and on postmarketing 
experience and are displayed by system organ class and frequency in Table 6 below: very common 
( 1/10); common ( 1/100 to < 1/10); uncommon ( 1/1,000 to < 1/100); rare ( 1/10,000 to < 1/1,000); 
and not known (cannot be estimated from the available data). Within each frequency grouping, 
undesirable effects are presented in order of decreasing seriousness. The highest frequency seen among the 
various indications has been included. An asterisk (*) appears in the SOC column if further information is 
found elsewhere in sections 4.3, 4.4 and 4.8. 
 

Table 6 
Undesirable Effects 

 

System Organ Class Frequency Adverse Reaction 

Infections and 
infestations* 

 

Very common Respiratory tract infections (including lower and 
upper respiratory tract infection, pneumonia, 
sinusitis, pharyngitis, nasopharyngitis and 
pneumonia herpes viral) 

Common 

 

Systemic infections (including sepsis, candidiasis 
and influenza), 
intestinal infections (including gastroenteritis 
viral), 
skin and soft tissue infections (including 
paronychia, cellulitis, impetigo, necrotising 
fasciitis and herpes zoster), 
ear infections, 
oral infections (including herpes simplex, oral 
herpes and tooth infections),  
reproductive tract infections (including 
vulvovaginal mycotic infection),  

urinary tract infections (including 
pyelonephritis), 

fungal infections, 

joint infections 



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System Organ Class Frequency Adverse Reaction 

Uncommon 
 

Neurological infections (including viral 
meningitis), 
opportunistic infections and tuberculosis 
(including coccidioidomycosis, histoplasmosis 
and mycobacterium avium complex infection),  
bacterial infections, 
eye infections, 
diverticulitis1)  

Neoplasms benign, 
malignant and unspecified 
(including cysts and 
polyps)* 

Common 

 

Skin cancer excluding melanoma (including 
basal cell carcinoma and squamous cell 
carcinoma), 

benign neoplasm 

Uncommon 
 

Lymphoma**,  
solid organ neoplasm (including breast cancer, 
lung neoplasm and thyroid neoplasm),  
melanoma** 

 Rare Leukaemia1) 

Not known Hepatosplenic T-cell lymphoma1) 

Merkel cell carcinoma (neuroendocrine 
carcinoma of the skin)1), 

Kaposi’s sarcoma 

Blood and the lymphatic 
system disorders* 

Very common 

 

Leukopenia (including neutropenia and 
agranulocytosis),  

anaemia 

 
Common Leucocytosis, 

thrombocytopenia 

Uncommon Idiopathic thrombocytopenic purpura 

Rare 
 

Pancytopenia 

Immune system disorders* Common 

 

Hypersensitivity, 

allergies (including seasonal allergy) 

Uncommon Sarcoidosis1), 

vasculitis 

Rare Anaphylaxis1) 

Metabolism and nutrition Very common Lipids increased



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System Organ Class Frequency Adverse Reaction 

disorders  

Common Hypokalaemia,  

uric acid increased,  

blood sodium abnormal, 

hypocalcaemia, 

hyperglycaemia, 

hypophosphatemia, 

dehydration 

Psychiatric disorders Common 

 

Mood alterations (including depression),  

anxiety, 

insomnia 

Nervous system disorders* Very common 

 

Headache 

Common 

 

Paraesthesias (including hypoesthesia), 

migraine, 

nerve root compression 

Uncommon 
 

Cerebrovascular accident1), 
tremor, 
neuropathy   

Rare 
 

Multiple sclerosis, 

demyelinating disorders (e.g. optic neuritis, 
Guillain-Barré syndrome) 1) 

Eye disorders Common 

 

Visual impairment, 

conjunctivitis, 

blepharitis, 

eye swelling 

Uncommon Diplopia 

Ear and labyrinth 
disorders  

 

Common 

 

Vertigo 

Uncommon 
 

Deafness,  
tinnitus 

Cardiac disorders*  Common Tachycardia 

Uncommon Myocardial infarction1),



16 

System Organ Class Frequency Adverse Reaction 

 arrhythmia, 

congestive heart failure 

Rare 
 

Cardiac arrest 

Vascular disorders Common 

 

Hypertension,  

flushing,  

haematoma 

Uncommon Aortic aneurysm, 
vascular arterial occlusion, 
thrombophlebitis    

Respiratory, thoracic and 
mediastinal disorders* 

Common 

 

Asthma, 

dyspnoea, 

cough 

Uncommon 
 

Pulmonary embolism1), 
interstitial lung disease,  
chronic obstructive pulmonary disease, 
pneumonitis, 
pleural effusion1) 

Rare Pulmonary fibrosis1)

Gastrointestinal disorders Very common 

 

Abdominal pain,  

nausea and vomiting 

Common 
 

GI haemorrhage,  
dyspepsia,  
gastroesophageal reflux disease, 
sicca syndrome 

Uncommon 
 

Pancreatitis,  
dysphagia, 
face oedema 

Rare Intestinal perforation1) 

Hepato-biliary disorders* Very Common 

 

Elevated liver enzymes 

Uncommon 
 

Cholecystitis and cholelithiasis, 
hepatic steatosis, 
bilirubin increased 

Rare Hepatitis



17 

System Organ Class Frequency Adverse Reaction 

 reactivation of hepatitis B1)  

autoimmune hepatitis1) 

Not known 

 

Liver failure1) 

Skin and subcutaneous 
tissue disorders 

Very Common 

 

Rash (including exfoliative rash) 

Common 
 

Worsening or new onset of psoriasis(including 
palmoplantar pustular psoriasis)1), 
urticaria, 
bruising (including purpura),  
dermatitis (including eczema), 
onychoclasis,  
hyperhidrosis, 
alopecia1), 
pruritus  

Uncommon 
 

Night sweats, 
scar 

Rare Erythema multiforme1), 

Stevens-Johnson syndrome1), 

angioedema1), 

cutaneous vasculitis1) 

lichenoid skin reaction1) 

Not known Worsening of symptoms of dermatomyositis1) 

Musculoskeletal and 
connective tissue disorders 

Very common 

 

Musculoskeletal pain 

Common Muscle spasms (including blood creatine 
phosphokinase increased) 

Uncommon Rhabdomyolysis, 
systemic lupus erythematosus 

Rare 
 

Lupus-like syndrome1)

Renal and urinary 
disorders  

Common 

 

Renal impairment, 

haematuria 

Uncommon 
 

Nocturia 

Reproductive system and 
breast disorders 

Uncommon Erectile dysfunction 



18 

System Organ Class Frequency Adverse Reaction 

General disorders and 
administration site 
conditions* 

Very Common 

 

Injection site reaction (including injection site 
erythema) 

Common 
 

Chest pain,  
oedema, 
pyrexia1) 

Uncommon 
 

Inflammation 

Investigations* Common Coagulation and bleeding disorders (including 
activated partial thromboplastin time prolonged), 

autoantibody test positive (including double 
stranded DNA antibody),  

blood lactate dehydrogenase increased 

Injury, poisoning and 
procedural complications 

Common Impaired healing 

 
* further information is found elsewhere in sections 4.3, 4.4 and 4.8 
** including open label extension studies 
1) including spontaneous reporting data 
 
Uveitis 
 
The safety profile for patients with uveitis treated with Humira every other week was consistent with the 
known safety profile of Humira. 
 
Description of selected adverse reactions 
 
Injection site reactions 
 
In the pivotal controlled trials in adults and children, 12.9% of patients treated with Humira developed 
injection site reactions (erythema and/or itching, haemorrhage, pain or swelling), compared to 7.2% of 
patients receiving placebo or active control. Injection site reactions generally did not necessitate 
discontinuation of the medicinal product. 
 
Infections  
 
In the pivotal controlled trials in adults and children, the rate of infection was 1.51 per patient year in the 
Humira treated patients and 1.46 per patient year in the placebo and active control-treated patients. The 
infections consisted primarily of nasopharyngitis, upper respiratory tract infection, and sinusitis. Most 
patients continued on Humira after the infection resolved.   
 
The incidence of serious infections was 0.04 per patient year in Humira treated patients and 0.03 per 
patient year in placebo and active control − treated patients.   
 
In controlled and open label adult and paediatric studies with Humira, serious infections (including fatal 
infections, which occurred rarely) have been reported, which include reports of tuberculosis (including 
miliary and extra-pulmonary locations) and invasive opportunistic infections (e.g. disseminated or 



19 

extrapulmonary histoplasmosis, blastomycosis, coccidioidomycosis, pneumocystis, candidiasis, 
aspergillosis and listeriosis). Most of the cases of tuberculosis occurred within the first eight months after 
initiation of therapy and may reflect recrudescence of latent disease. 
 
Malignancies and lymphoproliferative disorders 
 
No malignancies were observed in 249 paediatric patients with an exposure of 655.6 patient years during 
Humira trials in patients with juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and 
enthesitis-related arthritis). In addition, no malignancies were observed in 192 paediatric patients with an 
exposure of 498.1 patient years during Humira trials in paediatric patients with Crohn’s disease. No 
malignancies were observed in 77 paediatric patients with an exposure of 80.0 patient years during a 
Humira trial in paediatric patients with chronic plaque psoriasis. No malignancies were observed in 60 
paediatric patients with an exposure of 58.4 patient years during a Humira trial in paediatric patients with 
uveitis. 
 
During the controlled portions of pivotal Humira trials in adults of at least 12 weeks in duration in patients 
with moderately to severely active rheumatoid arthritis, ankylosing spondylitis, axial spondyloarthritis 
without radiographic evidence of AS, psoriatic arthritis, psoriasis, hidradenitis suppurativa, Crohn’s 
disease, ulcerative colitis and uveitis, malignancies, other than lymphoma and non-melanoma skin cancer, 
were observed at a rate (95% confidence interval) of 6.8 (4.4, 10.5) per 1,000 patient-years among 5,291 
Humira treated patients versus a rate of 6.3 (3.4, 11.8) per 1,000 patient-years among 3,444 control 
patients (median duration of treatment was 4.0 months for Humira and 3.8 months for control-treated 
patients). The rate (95% confidence interval) of non-melanoma skin cancers was 8.8 (6.0, 13.0) per 1,000 
patient-years among Humira-treated patients and 3.2 (1.3, 7.6) per 1,000 patient-years among control 
patients. Of these skin cancers, squamous cell carcinomas occurred at rates (95% confidence interval) of 
2.7 (1.4, 5.4) per 1,000 patient-years among Humira-treated patients and 0.6 (0.1, 4.5) per 1,000 patient-
years among control patients. The rate (95% confidence interval) of lymphomas was 0.7 (0.2, 2.7) per 
1,000 patient-years among Humira-treated patients and 0.6 (0.1, 4.5) per 1,000 patient-years among 
control patients. 
 
When combining controlled portions of these trials and ongoing and completed open label extension 
studies with a median duration of approximately 3.3 years including 6,427 patients and over 26,439 
patient-years of therapy, the observed rate of malignancies, other than lymphoma and non-melanoma skin 
cancers is approximately 8.5 per 1,000 patient years. The observed rate of non-melanoma skin cancers is 
approximately 9.6 per 1,000 patient years, and the observed rate of lymphomas is approximately 1.3 per 
1,000 patient years. 
 
In post-marketing experience from January 2003 to December 2010, predominantly in patients with 
rheumatoid arthritis, the reported rate of malignancies is approximately 2.7 per 1,000 patient treatment 
years. The reported rates for non-melanoma skin cancers and lymphomas are approximately 0.2 and 0.3 
per 1,000 patient treatment years, respectively (see section 4.4). 
 
Rare post-marketing cases of hepatosplenic T-cell lymphoma have been reported in patients treated with 
adalimumab (see section 4.4). 
 
Autoantibodies  
 
Patients had serum samples tested for autoantibodies at multiple time points in rheumatoid arthritis studies 
I − V. In these trials, 11.9% of patients treated with Humira and 8.1% of placebo and active 
control − treated patients that had negative baseline anti-nuclear antibody titres reported positive titres at 
Week 24. Two patients out of 3,441 treated with Humira in all rheumatoid arthritis and psoriatic arthritis 
studies developed clinical signs suggestive of new-onset lupus-like syndrome. The patients improved 



20 

following discontinuation of therapy. No patients developed lupus nephritis or central nervous system 
symptoms. 
 
Hepato-biliary events 
 
In controlled Phase 3 trials of Humira in patients with rheumatoid arthritis and psoriatic arthritis with a 
control period duration ranging from 4 to 104 weeks, ALT elevations ≥ 3 x ULN occurred in 3.7% of 
Humira-treated patients and 1.6% of control-treated patients.  
 
In controlled Phase 3 trials of Humira in patients with polyarticular juvenile idiopathic arthritis who were 
4 to 17 years and enthesitis-related arthritis who were 6 to 17 years, ALT elevations ≥ 3 x ULN occurred 
in 6.1% of Humira-treated patients and 1.3% of control-treated patients. Most ALT elevations occurred 
with concomitant methotrexate use. No ALT elevations ≥ 3 x ULN occurred in the Phase 3 trial of Humira 
in patients with polyarticular juvenile idiopathic arthritis who were 2 to < 4 years. 
 
In controlled Phase 3 trials of Humira in patients with Crohn’s disease and ulcerative colitis with a control 
period ranging from 4 to 52 weeks. ALT elevations ≥ 3 x ULN occurred in 0.9% of Humira-treated 
patients and 0.9% of controlled-treated patients.  
 
In the Phase 3 trial of Humira in patients with paediatric Crohn’s disease which evaluated efficacy and 
safety of two body weight adjusted maintenance dose regimens following body weight adjusted induction 
therapy up to 52 weeks of treatment, ALT elevations ≥ 3 x ULN occurred in 2.6% (5/192) of patients of 
whom 4 were receiving concomitant immunosuppressants at baseline. 
 
In controlled Phase 3 trials of Humira in patients with plaque psoriasis with a control period duration 
ranging from 12 to 24 weeks, ALT elevations ≥ 3 x ULN occurred in 1.8% of Humira-treated patients and 
1.8% of control-treated patients.  
 
No ALT elevations ≥ 3 x ULN occurred in the Phase 3 trial of Humira in paediatric patients with plaque 
psoriasis. 
 
In controlled trials of Humira (initial doses of 80 mg at Week 0 followed by 40 mg every other week 
starting at Week 1) in adult patients with uveitis up to 80 weeks with a median exposure of 166.5 days and 
105.0 days in Humira-treated and control-treated patients, respectively, ALT elevations ≥ 3 x ULN 
occurred in 2.4% of Humira-treated patients and 2.4% of control-treated patients.  
 
Across all indications in clinical trials patients with raised ALT were asymptomatic and in most cases 
elevations were transient and resolved on continued treatment. However, there have also been post-
marketing reports of liver failure as well as less severe liver disorders that may precede liver failure, such 
as hepatitis including autoimmune hepatitis in patients receiving adalimumab. 
 
Concurrent treatment with azathioprine/6-mercaptopurine 
 
In adult Crohn’s disease studies, higher incidences of malignant and serious infection-related adverse 
events were seen with the combination of Humira and azathioprine/6-mercaptopurine compared with 
Humira alone. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 
continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are 
asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.  
 



21 

4.9 Overdose 
 
No dose-limiting toxicity was observed during clinical trials. The highest dose level evaluated has been 
multiple intravenous doses of 10 mg/kg, which is approximately 15 times the recommended dose.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunosuppressants, Tumour Necrosis Factor alpha (TNF-α) inhibitors. 
ATC code: L04AB04 
 
Mechanism of action 
 
Adalimumab binds specifically to TNF and neutralises the biological function of TNF by blocking its 
interaction with the p55 and p75 cell surface TNF receptors.   
 
Adalimumab also modulates biological responses that are induced or regulated by TNF, including changes 
in the levels of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, and ICAM-1 
with an IC50 of 0.1-0.2 nM).  
 
Pharmacodynamic effects  
 
After treatment with Humira, a rapid decrease in levels of acute phase reactants of inflammation 
(C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) and serum cytokines (IL-6) was 
observed, compared to baseline in patients with rheumatoid arthritis. Serum levels of matrix 
metalloproteinases (MMP-1 and MMP-3) that produce tissue remodelling responsible for cartilage 
destruction were also decreased after Humira administration. Patients treated with Humira usually 
experienced improvement in haematological signs of chronic inflammation. 
 
A rapid decrease in CRP levels was also observed in patients with polyarticular juvenile idiopathic 
arthritis, Crohn’s disease, ulcerative colitis and hidradenitis suppurativa after treatment with Humira. In 
patients with Crohn’s disease, a reduction of the number of cells expressing inflammatory markers in the 
colon including a significant reduction of expression of TNFα was seen. Endoscopic studies in intestinal 
mucosa have shown evidence of mucosal healing in adalimumab treated patients. 
 
Clinical efficacy and safety 
 
Adults with rheumatoid arthritis 
 
Humira was evaluated in over 3,000 patients in all rheumatoid arthritis clinical trials. The efficacy and 
safety of Humira were assessed in five randomised, double-blind and well-controlled studies. Some 
patients were treated for up to 120 months duration.  
 
RA study I evaluated 271 patients with moderately to severely active rheumatoid arthritis who were 
 18 years old, had failed therapy with at least one disease-modifying, anti rheumatic drug and had 
insufficient efficacy with methotrexate at doses of 12.5 to 25 mg (10 mg if methotrexate-intolerant) every 
week and whose methotrexate dose remained constant at 10 to 25 mg every week. Doses of 20, 40 or 
80 mg of Humira or placebo were given every other week for 24 weeks.  
 
RA study II evaluated 544 patients with moderately to severely active rheumatoid arthritis who were 
 18 years old and had failed therapy with at least one disease-modifying, anti-rheumatic drugs. Doses of 



22 

20 or 40 mg of Humira were given by subcutaneous injection every other week with placebo on alternative 
weeks or every week for 26 weeks; placebo was given every week for the same duration. No other 
disease-modifying anti-rheumatic drugs were allowed. 
 
RA study III evaluated 619 patients with moderately to severely active rheumatoid arthritis who were 
 18 years old, and who had an ineffective response to methotrexate at doses of 12.5 to 25 mg or have 
been intolerant to 10 mg of methotrexate every week. There were three groups in this study. The first 
received placebo injections every week for 52 weeks. The second received 20 mg of Humira every week 
for 52 weeks. The third group received 40 mg of Humira every other week with placebo injections on 
alternate weeks. Upon completion of the first 52 weeks, 457 patients enrolled in an open-label extension 
phase in which 40 mg of Humira/MTX was administered every other week up to 10 years. 
 
RA study IV primarily assessed safety in 636 patients with moderately to severely active rheumatoid 
arthritis who were  18 years old. Patients were permitted to be either disease-modifying, anti-rheumatic 
drug-naïve or to remain on their pre-existing rheumatologic therapy provided that therapy was stable for a 
minimum of 28 days. These therapies include methotrexate, leflunomide, hydroxychloroquine, 
sulfasalazine and/or gold salts. Patients were randomised to 40 mg of Humira or placebo every other week 
for 24 weeks.   
 
RA study V evaluated 799 methotrexate-naïve, adult patients with moderate to severely active early 
rheumatoid arthritis (mean disease duration less than 9 months). This study evaluated the efficacy of 
Humira 40 mg every other week/methotrexate combination therapy, Humira 40 mg every other week 
monotherapy and methotrexate monotherapy in reducing the signs and symptoms and rate of progression 
of joint damage in rheumatoid arthritis for 104 weeks. Upon completion of the first 104 weeks, 497 
patients enrolled in an open-label extension phase in which 40 mg of Humira was administered every 
other week up to 10 years. 
 
The primary end point in RA studies I, II and III and the secondary endpoint in RA study IV was the 
percent of patients who achieved an ACR 20 response at Week 24 or 26. The primary endpoint in RA 
study V was the percent of patients who achieved an ACR 50 response at Week 52. RA studies III and V 
had an additional primary endpoint at 52 weeks of retardation of disease progression (as detected by X-ray 
results). RA study III also had a primary endpoint of changes in quality of life.  
 
ACR response 
 
The percent of Humira-treated patients achieving ACR 20, 50 and 70 responses was consistent across RA 
studies I, II and III. The results for the 40 mg every other week dose are summarised in Table 7.  



23 

 
Table 7 

ACR Responses in Placebo-Controlled Trials 
(Percent of Patients) 

 
Response RA Study Ia** RA Study IIa** RA Study IIIa** 

 
 Placebo/ 

MTXc 
n=60 

Humirab/ MTXc

n=63 
Placebo 
n=110 

Humirab 
n=113 

Placebo/ 
MTXc 
n=200 

Humirab/ MTXc

n=207 

ACR 20    
 6 months 13.3% 65.1% 19.1% 46.0% 29.5% 63.3%
 12 months NA NA NA NA 24.0% 58.9%
ACR 50    
 6 months 6.7% 52.4% 8.2% 22.1% 9.5% 39.1%
 12 months NA NA NA NA 9.5% 41.5%
ACR 70    
 6 months 3.3% 23.8% 1.8% 12.4% 2.5% 20.8%
 12 months NA NA NA NA 4.5% 23.2%
a RA study I at 24 weeks, RA study II at 26 weeks , and RA study III at 24 and 52 weeks 
b 40 mg Humira administered every other week 
c MTX = methotrexate 
**p < 0.01, Humira versus placebo 

 
In RA studies I-IV, all individual components of the ACR response criteria (number of tender and swollen 
joints, physician and patient assessment of disease activity and pain, disability index (HAQ) scores and 
CRP (mg/dl) values) improved at 24 or 26 weeks compared to placebo. In RA study III, these 
improvements were maintained throughout 52 weeks.  
 
In the open-label extension for RA study III, most patients who were ACR responders maintained 
response when followed for up to 10 years. Of 207 patients who were randomised to Humira 40 mg every 
other week, 114 patients continued on Humira 40 mg every other week for 5 years. Among those, 86 
patients (75.4%) had ACR 20 responses; 72 patients (63.2%) had ACR 50 responses; and 41 patients 
(36%) had ACR 70 responses. Of 207 patients, 81 patients continued on Humira 40 mg every other week 
for 10 years. Among those, 64 patients (79.0%) had ACR 20 responses; 56 patients (69.1%) had ACR 50 
responses; and 43 patients (53.1%) had ACR 70 responses. 
 
In RA study IV, the ACR 20 response of patients treated with Humira plus standard of care was 
statistically significantly better than patients treated with placebo plus standard of care (p < 0.001).   
 
In RA studies I-IV, Humira-treated patients achieved statistically significant ACR 20 and 50 responses 
compared to placebo as early as one to two weeks after initiation of treatment. 
 
In RA study V with early rheumatoid arthritis patients who were methotrexate naïve, combination therapy 
with Humira and methotrexate led to faster and significantly greater ACR responses than methotrexate 
monotherapy and Humira monotherapy at Week 52 and responses were sustained at Week 104 (see Table 
8). 



24 

 
Table 8 

ACR Responses in RA Study V 
(percent of patients) 

 

Response 
MTX 
n=257 

Humira 
n=274 

Humira/MTX 
n=268 

p-valuea p-valueb p-valuec 

ACR 20   
 Week 
52 

62.6% 54.4% 72.8% 0.013 < 0.001 0.043 

 Week 
104 

56.0% 49.3% 69.4% 0.002 < 0.001 0.140 

ACR 50   
 Week 
52 

45.9% 41.2% 61.6% < 0.001 < 0.001 0.317 

 Week 
104 

42.8% 36.9% 59.0% < 0.001 < 0.001 0.162 

ACR 70   
 Week 
52 

27.2% 25.9% 45.5% < 0.001 < 0.001 0.656 

 Week 
104 

28.4% 28.1% 46.6% < 0.001 < 0.001 0.864 

a. p-value is from the pairwise comparison of methotrexate monotherapy and Humira/methotrexate 
combination therapy using the Mann-Whitney U test. 

b. p-value is from the pairwise comparison of Humira monotherapy and Humira/methotrexate 
combination therapy using the Mann-Whitney U test 

c.   p-value is from the pairwise comparison of Humira monotherapy and methotrexate monotherapy 
using the Mann-Whitney U test 

 
In the open-label extension for RA study V, ACR response rates were maintained when followed for up to 
10 years. Of 542 patients who were randomised to Humira 40 mg every other week, 170 patients 
continued on Humira 40 mg every other week for 10 years. Among those, 154 patients (90.6%) had ACR 
20 responses; 127 patients (74.7%) had ACR 50 responses; and 102 patients (60.0%) had ACR 70 
responses. 
 
At Week 52, 42.9% of patients who received Humira/methotrexate combination therapy achieved clinical 
remission (DAS28 (CRP) < 2.6) compared to 20.6% of patients receiving methotrexate monotherapy and 
23.4% of patients receiving Humira monotherapy. Humira/methotrexate combination therapy was 
clinically and statistically superior to methotrexate (p < 0.001) and Humira monotherapy (p < 0.001) in 
achieving a low disease state in patients with recently diagnosed moderate to severe rheumatoid arthritis. 
The response for the two monotherapy arms was similar (p = 0.447). Of 342 subjects originally 
randomized to Humira monotherapy or Humira/methotrexate combination therapy who entered the open-
label extension study, 171 subjects completed 10 years of Humira treatment. Among those, 109 subjects 
(63.7%) were reported to be in remission at 10 years. 
 
Radiographic response 
 
In RA study III, where Humira treated patients had a mean duration of rheumatoid arthritis of 
approximately 11 years, structural joint damage was assessed radiographically and expressed as change in 
modified Total Sharp Score (TSS) and its components, the erosion score and joint space narrowing score. 
Humira/methotrexate patients demonstrated significantly less radiographic progression than patients 
receiving methotrexate alone at 6 and 12 months (see Table 9).   
 



25 

In the open-label extension of RA Study III, the reduction in rate of progression of structural damage is 
maintained for 8 and 10 years in a subset of patients. At 8 years, 81 of 207 patients originally treated with 
40 mg Humira every other week were evaluated radiographically. Among those, 48 patients showed no 
progression of structural damage defined by a change from baseline in the mTSS of 0.5 or less. At 
10 years, 79 of 207 patients originally treated with 40 mg Humira every other week were evaluated 
radiographically. Among those, 40 patients showed no progression of structural damage defined by a 
change from baseline in the mTSS of 0.5 or less. 
 

Table 9 
 Radiographic Mean Changes Over 12 Months in RA Study III 

 
 Placebo/ 

MTXa 
Humira/MTX 
40 mg every 
other week 

Placebo/MTX-
Humira/MTX (95% 

Confidence 
Intervalb)

p-value 

Total Sharp Score 2.7 0.1 2.6 (1.4, 3.8) < 0.001c 

Erosion score 1.6 0.0 1.6 (0.9, 2.2) < 0.001 
JSNd score 1.0 0.1 0.9 (0.3, 1.4)   0.002 

amethotrexate 
b95% confidence intervals for the differences in change scores between methotrexate and Humira.  
cBased on rank analysis  
dJoint Space Narrowing 
 
In RA study V, structural joint damage was assessed radiographically and expressed as change in modified 
Total Sharp Score (see Table 10). 
 

Table 10 
  Radiographic Mean Changes at Week 52 in RA Study V 

 

 

MTX 
n=257 
(95% 

confidence 
interval) 

Humira 
n=274 
(95% 

confidence 
interval)

Humira/MTX 
n=268 
(95% 

confidence 
interval)

p-valuea p-valueb p-valuec 

Total Sharp 
Score 

5.7 (4.2-7.3) 3.0 (1.7-4.3) 1.3 (0.5-2.1) < 0.001 0.0020 < 0.001 

Erosion score 3.7 (2.7-4.7) 1.7 (1.0-2.4) 0.8 (0.4-1.2) < 0.001 0.0082 < 0.001
JSN score 2.0 (1.2-2.8) 1.3 (0.5-2.1) 0.5 (0-1.0) < 0.001 0.0037 0.151

a p-value is from the pairwise comparison of methotrexate monotherapy and Humira/methotrexate 
combination therapy using the Mann-Whitney U test. 

b p-value is from the pairwise comparison of Humira monotherapy and Humira/methotrexate 
combination therapy using the Mann-Whitney U test  

c p-value is from the pairwise comparison of Humira monotherapy and methotrexate monotherapy 
using the Mann-Whitney U test 

 
Following 52 weeks and 104 weeks of treatment, the percentage of patients without progression (change 
from baseline in modified Total Sharp Score  0.5) was significantly higher with Humira/methotrexate 
combination therapy (63.8% and 61.2% respectively) compared to methotrexate monotherapy (37.4% and 
33.5% respectively, p < 0.001) and Humira monotherapy (50.7%, p < 0.002 and 44.5%, p < 0.001 
respectively). 
 
In the open-label extension of RA study V, the mean change from baseline at Year 10 in the modified 
Total Sharp Score was 10.8, 9.2 and 3.9 in patients originally randomized to methotrexate monotherapy, 



26 

Humira monotherapy and Humira/methotrexate combination therapy, respectively. The corresponding 
proportions of patients with no radiographic progression were 31.3%, 23.7% and 36.7% respectively. 
 
Quality of life and physical function  
 
Health-related quality of life and physical function were assessed using the disability index of the Health 
Assessment Questionnaire (HAQ) in the four original adequate and well-controlled trials, which was a 
pre-specified primary endpoint at Week 52 in RA study III. All doses/schedules of Humira in all four 
studies showed statistically significantly greater improvement in the disability index of the HAQ from 
baseline to Month 6 compared to placebo and in RA study III the same was seen at Week 52. Results from 
the Short Form Health Survey (SF 36) for all doses/schedules of Humira in all four studies support these 
findings, with statistically significant physical component summary (PCS) scores, as well as statistically 
significant pain and vitality domain scores for the 40 mg every other week dose. A statistically significant 
decrease in fatigue as measured by functional assessment of chronic illness therapy (FACIT) scores was 
seen in all three studies in which it was assessed (RA studies I, III, IV). 
 
In RA study III, most subjects who achieved improvement in physical function and continued treatment 
maintained improvement through Week 520 (120 months) of open-label treatment. Improvement in 
quality of life was measured up to Week 156 (36 months) and improvement was maintained through that 
time. 
 
In RA study V, the improvement in the HAQ disability index and the physical component of the SF 36 
showed greater improvement (p < 0.001) for Humira/methotrexate combination therapy versus 
methotrexate monotherapy and Humira monotherapy at Week 52, which was maintained through 
Week 104. Among the 250 subjects who completed the open-label extension study, improvements in 
physical function were maintained through 10 years of treatment. 
 
Adult plaque psoriasis  
 
The safety and efficacy of Humira were studied in adult patients with chronic plaque psoriasis ( 10% 
BSA involvement and PASI  12 or  10) who were candidates for systemic therapy or phototherapy in 
randomised, double-blind studies. 73% of patients enrolled in Psoriasis Studies I and II had received prior 
systemic therapy or phototherapy. The safety and efficacy of Humira were also studied in adult patients 
with moderate to severe chronic plaque psoriasis with concomitant hand and/or foot psoriasis who were 
candidates for systemic therapy in a randomised double-blind study (Psoriasis Study III).   
 
Psoriasis Study I (REVEAL) evaluated 1,212 patients within three treatment periods. In period A, patients 
received placebo or Humira at an initial dose of 80 mg followed by 40 mg every other week starting one 
week after the initial dose. After 16 weeks of therapy, patients who achieved at least a PASI 75 response 
(PASI score improvement of at least 75% relative to baseline), entered period B and received open-label 
40 mg Humira every other week. Patients who maintained PASI 75 response at Week 33 and were 
originally randomised to active therapy in Period A, were re-randomised in period C to receive 40 mg 
Humira every other week or placebo for an additional 19 weeks. Across all treatment groups, the mean 
baseline PASI score was 18.9 and the baseline PGA score ranged from “moderate” (53% of subjects 
included) to “severe” (41%) to “very severe” (6%). 
 
Psoriasis Study II (CHAMPION) compared the efficacy and safety of Humira versus methotrexate and 
placebo in 271 patients. Patients received placebo, an initial dose of MTX 7.5 mg and thereafter dose 
increases up to Week 12, with a maximum dose of 25 mg or an initial dose of 80 mg Humira followed by 
40 mg every other week (starting one week after the initial dose) for 16 weeks. There are no data available 
comparing Humira and MTX beyond 16 weeks of therapy. Patients receiving MTX who achieved a 
PASI 50 response at Week 8 and/or 12 did not receive further dose increases. Across all treatment 



27 

groups, the mean baseline PASI score was 19.7 and the baseline PGA score ranged from “mild” (<1%) to 
“moderate” (48%) to “severe” (46%) to “very severe” (6%). 
 
Patients participating in all Phase 2 and Phase 3 psoriasis studies were eligible to enrol into an open-label 
extension trial, where Humira was given for at least an additional 108 weeks. 
 
In Psoriasis Studies I and II, a primary endpoint was the proportion of patients who achieved a PASI 75 
response from baseline at Week 16 (see Tables 11 and 12). 
 

Table 11 
Ps Study I (REVEAL)  - Efficacy Results at 16 Weeks 

 
Placebo 
N=398 
n (%) 

Humira 40 mg eow 
N=814 
n (%) 

     PASI 75a 26 (6.5) 578 (70.9)b 
    PASI 100 3 (0.8) 163 (20.0)b 
    PGA: Clear/minimal 17 (4.3) 506 (62.2)b 
a Percent of patients achieving PASI75 response was calculated as centre-
adjusted rate 
b p < 0.001, Humira vs. Placebo

 

Table 12 
 Ps Study II (CHAMPION) Efficacy Results at 16 Weeks 

 Placebo 
N=53 
n (%) 

MTX 
N=110 
n (%) 

Humira 40 mg eow 
N=108 
n (%) 

     PASI 75 10 (18.9) 39 (35.5) 86 (79.6) a, b 
    PASI 100 1 (1.9) 8 (7.3) 18 (16.7) c, d 
    PGA: 
Clear/minimal 

6 (11.3) 33 (30.0) 79 (73.1) a, b 

a p < 0.001 Humira vs. placebo 
b p < 0.001 Humira vs. methotrexate 
c p < 0.01 Humira vs. placebo 
d p < 0.05 Humira vs. methotrexate

 
In Psoriasis Study I, 28% of patients who were PASI 75 responders and were re-randomised to placebo at 
Week 33 compared to 5% continuing on Humira, p < 0.001, experienced “loss of adequate response” 
(PASI score after Week 33 and on or before Week 52 that resulted in a <PASI 50 response relative to 
baseline with a minimum of a 6-point increase in PASI score relative to Week 33). Of the patients who 
lost adequate response after re-randomisation to placebo who then enrolled into the open-label extension 
trial, 38% (25/66) and 55% (36/66) regained PASI 75 response after 12 and 24 weeks of re-treatment, 
respectively. 
 
A total of 233 PASI 75 responders at Week 16 and Week 33 received continuous Humira therapy for 
52 weeks in Psoriasis Study I, and continued Humira in the open-label extension trial. PASI 75 and PGA 
of clear or minimal response rates in these patients were 74.7% and 59.0%, respectively, after an 
additional 108 weeks of open-label therapy (total of 160 weeks). In an analysis in which all patients who 
dropped out of the study for adverse events or lack of efficacy, or who dose-escalated, were considered 
non-responders, PASI 75 and PGA of clear or minimal response rates in these patients were 69.6% and 
55.7%, respectively, after an additional 108 weeks of open-label therapy (total of 160 weeks). 
 



28 

A total of 347 stable responders participated in a withdrawal and retreatment evaluation in an open-label 
extension study. During the withdrawal period, symptoms of psoriasis returned over time with a median 
time to relapse (decline to PGA “moderate” or worse) of approximately 5 months. None of these patients 
experienced rebound during the withdrawal period. A total of 76.5% (218/285) of patients who entered the 
retreatment period had a response of PGA “clear” or “minimal” after 16 weeks of retreatment, irrespective 
of whether they relapsed during withdrawal (69.1%[123/178] and 88.8% [95/107] for patients who 
relapsed and who did not relapse during the withdrawal period, respectively). A similar safety profile was 
observed during retreatment as before withdrawal. 
 
Significant improvements at Week 16 from baseline compared to placebo (Studies I and II) and MTX 
(Study II) were demonstrated in the DLQI (Dermatology Life Quality Index). In Study I, improvements in 
the physical and mental component summary scores of the SF-36 were also significant compared to 
placebo. 
 
In an open-label extension study, for patients who dose escalated from 40 mg every other week to 40 mg 
weekly due to a PASI response below 50%, 26.4% (92/349) and 37.8% (132/349) of patients achieved 
PASI 75 response at Week 12 and 24, respectively. 
 
Psoriasis Study III (REACH) compared the efficacy and safety of Humira versus placebo in 72 patients 
with moderate to severe chronic plaque psoriasis and hand and/or foot psoriasis. Patients received an 
initial dose of 80 mg Humira followed by 40 mg every other week (starting one week after the initial dose) 
or placebo for 16 weeks. At Week 16, a statistically significantly greater proportion of patients who 
received Humira achieved PGA of 'clear' or 'almost clear' for the hands and/or feet compared to patients 
who received placebo (30.6% versus 4.3%, respectively [P = 0.014]). 
 
Psoriasis Study IV compared efficacy and safety of Humira versus placebo in 217 adult patients with 
moderate to severe nail psoriasis. Patients received an initial dose of 80 mg Humira followed by 40 mg 
every other week (starting one week after the initial dose) or placebo for 26 weeks followed by open-label 
Humira treatment for an additional 26 weeks. Nail psoriasis assessments included the Modified Nail 
Psoriasis Severity Index (mNAPSI), the Physician’s Global Assessment of Fingernail Psoriasis (PGA-F) 
and the Nail Psoriasis Severity Index (NAPSI) (see Table 13). Humira demonstrated a treatment benefit in 
nail psoriasis patients with different extents of skin involvement (BSA≥10% (60% of patients) and 
BSA<10% and ≥5% (40% of patients)). 
 

Table 13 
Ps Study IV Efficacy Results at 16, 26 and 52 Weeks 

Endpoint Week 16 
Placebo-Controlled

Week 26 
Placebo-Controlled

Week 52 
Open-label 

Placebo 
N=108 

Humira 
40 mg eow 

N=109

Placebo
N=108 

Humira 
40 mg eow 

N=109

Humira 
40 mg eow  

N=80 
≥ mNAPSI 75 (%) 2.9 26.0a 3.4 46.6a 65.0 
PGA-F 
clear/minimal and 
≥2-grade 
improvement (%) 

2.9 29.7a 6.9 48.9a 61.3 

Percent Change in 
Total Fingernail 
NAPSI (%) 

-7.8 -44.2 a -11.5 -56.2a -72.2 

a p<0.001, Humira vs. placebo  
 
Humira treated patients showed statistically significant improvements at Week 26 compared with placebo 
in the DLQI.  



29 

 
 
Adult Crohn’s disease 
 
The safety and efficacy of Humira were assessed in over 1500 patients with moderately to severely active 
Crohn’s disease (Crohn’s Disease Activity Index (CDAI)  220 and  450) in randomised, double-blind, 
placebo-controlled studies. Concomitant stable doses of aminosalicylates, corticosteroids, and/or 
immunomodulatory agents were permitted and 80% of patients continued to receive at least one of these 
medications.  
 
Induction of clinical remission (defined as CDAI < 150) was evaluated in two studies, CD Study I 
(CLASSIC I) and CD Study II (GAIN). In CD Study I, 299 TNF-antagonist naive patients were 
randomised to one of four treatment groups; placebo at Weeks 0 and 2, 160 mg Humira at Week 0 and 
80 mg at Week 2, 80 mg at Week 0 and 40 mg at Week 2, and 40 mg at Week 0 and 20 mg at Week 2. In 
CD Study II, 325 patients who had lost response or were intolerant to infliximab were randomised to 
receive either 160 mg Humira at Week 0 and 80 mg at Week 2 or placebo at Weeks 0 and 2. The primary 
non-responders were excluded from the studies and therefore these patients were not further evaluated. 
 
Maintenance of clinical remission was evaluated in CD study III (CHARM). In CD Study III, 854 patients 
received open-label 80 mg at Week 0 and 40 mg at Week 2. At Week 4 patients were randomised to 
40 mg every other week, 40 mg every week, or placebo with a total study duration of 56 weeks. Patients in 
clinical response (decrease in CDAI ≥ 70) at Week 4 were stratified and analysed separately from those 
not in clinical response at Week 4. Corticosteroid taper was permitted after Week 8.  
 
CD study I and CD study II induction of remission and response rates are presented in Table 14. 
 

Table 14 
Induction of Clinical Remission and Response 

(Percent of Patients) 

 CD Study I: Infliximab Naive 
Patients 

CD Study II: Infliximab 
Experienced Patients 

 Placebo 
N=74 

Humira 
80/40 mg 

N = 75 

Humira  
160/80 mg 

N=76 

Placebo 
N=166 

Humira  
160/80 mg 

N=159 

Week 4      

Clinical remission 12% 24% 36%* 7% 21%* 

Clinical response (CR-
100) 

24% 37% 49%** 25% 38%** 

All p-values are pairwise comparisons of proportions for Humira versus placebo 
* p < 0.001 
** p < 0.01 

 
Similar remission rates were observed for the 160/80 mg and 80/40 mg induction regimens by Week 8 and 
adverse events were more frequently noted in the 160/80 mg group. 
 
In CD Study III, at Week 4, 58% (499/854) of patients were in clinical response and were assessed in the 
primary analysis. Of those in clinical response at Week 4, 48% had been previously exposed to other TNF-
antagonists. Maintenance of remission and response rates are presented in Table 15. Clinical remission 
results remained relatively constant irrespective of previous TNF-antagonist exposure. 
 



30 

Disease-related hospitalisations and surgeries were statistically significantly reduced with adalimumab 
compared with placebo at Week 56. 
 

Table 15 
Maintenance of Clinical Remission and Response 

(Percent of Patients) 

 Placebo 40 mg Humira 
every other week 

40 mg Humira
every week 

Week 26 N=170 N=172 N=157 

Clinical remission 17% 40%* 47%* 

Clinical response (CR-100) 27% 52%* 52%* 

Patients in steroid-free remission  
for >=90 daysa 

3% (2/66) 19% (11/58)** 15% (11/74)** 

Week 56 N=170 N=172 N=157 

Clinical remission 12% 36%* 41%* 

Clinical response (CR-100) 17% 41%* 48%* 

Patients in steroid-free remission  
for > = 90 daysa 

5% (3/66) 29% (17/58)* 20% (15/74)** 

* p < 0.001 for Humira versus placebo pairwise comparisons of proportions 
** p < 0.02 for Humira versus placebo pairwise comparisons of proportions 
a Of those receiving corticosteroids at baseline 

 
Among patients who were not in response at Week 4, 43% of Humira maintenance patients responded by 
Week 12 compared to 30% of placebo maintenance patients. These results suggest that some patients who 
have not responded by Week 4 benefit from continued maintenance therapy through Week 12. Therapy 
continued beyond 12 weeks did not result in significantly more responses (see section 4.2).   
 
117/276 patients from CD study I and 272/777 patients from CD studies II and III were followed through 
at least 3 years of open-label adalimumab therapy. 88 and 189 patients, respectively, continued to be in 
clinical remission. Clinical response (CR-100) was maintained in 102 and 233 patients, respectively. 
 
Quality of life 
 
In CD Study I and CD Study II, statistically significant improvement in the disease-specific inflammatory 
bowel disease questionnaire (IBDQ) total score was achieved at Week 4 in patients randomised to Humira 
80/40 mg and 160/80 mg compared to placebo and was seen at Weeks 26 and 56 in CD Study III as well 
among the adalimumab treatment groups compared to the placebo group. 
 
Adult Uveitis 
 
The safety and efficacy of Humira were assessed in adult patients with non-infectious intermediate, 
posterior, and panuveitis, excluding patients with isolated anterior uveitis, in two randomised, double-
masked, placebo-controlled studies (UV I and II). Patients received placebo or Humira at an initial dose of 
80 mg followed by 40 mg every other week starting one week after the initial dose. Concomitant stable 
doses of one non-biologic immunosuppressant were permitted.  
 
Study UV I evaluated 217 patients with active uveitis despite treatment with corticosteroids (oral 
prednisone at a dose of 10 to 60 mg/day). All patients received a 2-week standardised dose of prednisone 
60 mg/day at study entry followed by a mandatory taper schedule, with complete corticosteroid 
discontinuation by Week 15.  



31 

 
Study UV II evaluated 226 patients with inactive uveitis requiring chronic corticosteroid treatment (oral 
prednisone 10 to 35 mg/day) at baseline to control their disease. Patients subsequently underwent a 
mandatory taper schedule, with complete corticosteroid discontinuation by Week 19.  
 
The primary efficacy endpoint in both studies was ´time to treatment failure´. Treatment failure was 
defined by a multi-component outcome based on inflammatory chorioretinal and/or inflammatory retinal 
vascular lesions, anterior chamber (AC) cell grade, vitreous haze (VH) grade and best corrected visual 
acuity (BCVA).  
 
Patients who completed Studies UV I and UV II were eligible to enroll in an uncontrolled long-term 
extension study with an originally planned duration of 78 weeks. Patients were allowed to continue on 
study medication beyond Week 78 until they had access to Humira. 
 
Clinical Response 
 
Results from both studies demonstrated statistically significant reduction of the risk of treatment failure in 
patients treated with Humira versus patients receiving placebo (See Table 16). Both studies demonstrated 
an early and sustained effect of Humira on the treatment failure rate versus placebo (see Figure 1).  
 

Table 16  
Time to Treatment Failure in Studies UV I and UV II 

 
Analysis 
 Treatment 

N Failure 
N (%) 

Median Time to 
Failure (months) 

HRa CI 95% 
for HRa 

P Value b 

Time to Treatment Failure At or After Week 6 in Study UV I   
Primary analysis (ITT)   
 Placebo 107 84 (78.5) 3.0 -- -- -- 
 Adalimumab 110 60 (54.5) 5.6 0.50 0.36, 0.70  < 0.001
Time to Treatment Failure At or After Week 2 in Study UV II 
Primary analysis (ITT)   
 Placebo 111 61 (55.0) 8.3 -- -- -- 
 Adalimumab 115 45 (39.1) NEc 0.57 0.39, 0.84 0.004 

Note: Treatment failure at or after Week 6 (Study UV I), or at or after Week 2 (Study UV II), was counted 
as event. Drop outs due to reasons other than treatment failure were censored at the time of dropping out. 
a HR of adalimumab vs placebo from proportional hazards regression with treatment as factor. 
b 2-sided P value from log rank test. 
c NE = not estimable. Fewer than half of at-risk subjects had an event.  
 



32 

Figure 1: Kaplan-Meier Curves Summarizing Time to Treatment Failure on or after Week 6 (Study 
UV I) or Week 2 (Study UV II)  

 

T
R

E
A

T
M

E
N

T
 F

A
IL

U
R

E
 R

A
T

E
 (

%
) 

 TIME (MONTHS)
 Study UV I                        Treatment Placebo Adalimumab 

T
R

E
A

T
M

E
N

T
 F

A
IL

U
R

E
 R

A
T

E
 (

%
) 

 TIME (MONTHS)
 Study UV II                       Treatment Placebo Adalimumab 

Note: P# = Placebo (Number of Events/Number at Risk); A# = HUMIRA (Number of 
Events/Number at Risk). 

 
In Study UV I statistically significant differences in favour of adalimumab versus placebo were observed 
for each component of treatment failure. In Study UV II, statistically significant differences were observed 
for visual acuity only, but the other components were numerically in favour of adalimumab. 
 
Of the 424 subjects included in the uncontrolled long-term extension of Studies UV I and UV II, 60 
subjects were regarded ineligible (e.g. due to deviations or due to complications secondary to diabetic 
retinopathy, due to cataract surgery or vitrectomy) and were excluded from the primary analysis of 
efficacy. Of the 364 remaining patients, 269 evaluable patients (74%) reached 78 weeks of open-label 
adalimumab treatment. Based on the observed data approach, 216 (80.3%) were in quiescence (no active 
inflammatory lesions, AC cell grade  ≤ 0.5+, VH grade ≤ 0.5+) with a concomitant steroid dose ≤ 7.5 mg 
per day, and 178 (66.2%) were in steroid-free quiescence. BCVA was either improved or maintained (< 5 
letters deterioration) in 88.6% of the eyes at week 78. Data beyond Week 78 were generally consistent 



33 

with these results but the number of enrolled subjects declined after this time. Overall, among the patients 
who discontinued the study, 18% discontinued due to adverse events, and 8% due to insufficient response 
to adalimumab treatment. 
 
Quality of Life 
 
Patient reported outcomes regarding vision-related functioning were measured in both clinical studies, 
using the NEI VFQ-25. Humira was numerically favoured for the majority of subscores with statistically 
significant mean differences for general vision, ocular pain, near vision, mental health, and total score in 
Study UV I, and for general vision and mental health in Study UV II. Vision related effects were not 
numerically in favour of Humira for colour vision in Study UVI and for colour vision, peripheral vision 
and near vision in Study UV II. 
 
Immunogenicity 
 
Formation of anti-adalimumab antibodies is associated with increased clearance and reduced efficacy of 
adalimumab. There is no apparent correlation between the presence of anti-adalimumab antibodies and the 
occurrence of adverse events. 
 
In patients with polyarticular juvenile idiopathic arthritis who were 4 to 17 years, anti-adalimumab 
antibodies were identified in 15.8% (27/171) of patients treated with adalimumab. In patients not given 
concomitant methotrexate, the incidence was 25.6% (22/86) compared to 5.9% (5/85) when adalimumab 
was used as add-on to methotrexate. In patients with polyarticular juvenile idiopathic arthritis who were 
2 to < 4 years old or aged 4 and above weighing <15 kg, anti-adalimumab antibodies were identified in 
7% (1/15) of patients, and the one patient was receiving concomitant methotrexate. 
 
In patients with enthesitis-related arthritis, anti-adalimumab antibodies were identified in 10.9% (5/46) of 
patients treated with adalimumab. In patients not given concomitant methotrexate, the incidence was 
13.6% (3/22), compared to 8.3% (2/24) when adalimumab was used as add-on to methotrexate. 
 
Patients in rheumatoid arthritis studies I, II and III were tested at multiple time points for anti-adalimumab 
antibodies during the 6 to 12 month period. In the pivotal trials, anti-adalimumab antibodies were 
identified in 5.5% (58/1053) of patients treated with adalimumab, compared to 0.5% (2/370) on placebo. 
In patients not given concomitant methotrexate, the incidence was 12.4%, compared to 0.6% when 
adalimumab was used as add-on to methotrexate.   
 
In patients with paediatric psoriasis, anti-adalimumab antibodies were identified in 5/38 subjects (13%) 
treated with 0.8 mg/kg adalimumab monotherapy. 
 
In adult patients with psoriasis, anti-adalimumab antibodies were identified in 77/920 subjects (8.4%) 
treated with adalimumab monotherapy. 
 
In adult plaque psoriasis patients on long term adalimumab monotherapy who participated in a withdrawal 
and retreatment study, the rate of antibodies to adalimumab after retreatment (11 of 482 subjects, 2.3%) 
was similar to the rate observed prior to withdrawal (11 of 590 subjects, 1.9%). 
 
In patients with moderately to severely active paediatric Crohn’s disease, the rate of anti-adalimumab 
antibody development in patients receiving adalimumab was 3.3%.  
 
In patients with Crohn’s disease, anti-adalimumab antibodies were identified in 7/269 subjects (2.6%). 
 
In adult patients with non-infectious uveitis, anti-adalimumab antibodies were identified in 4.8% (12/249) 
of patients treated with adalimumab. 



34 

 
Because immunogenicity analyses are product-specific, comparison of antibody rates with those from 
other products is not appropriate. 
 
Paediatric population 
 
Juvenile idiopathic arthritis (JIA) 
 
Polyarticular juvenile idiopathic arthritis (pJIA) 
 
The safety and efficacy of Humira was assessed in two studies (pJIA I and II) in children with active 
polyarticular or polyarticular course juvenile idiopathic arthritis, who had a variety of JIA onset types 
(most frequently rheumatoid-factor negative or positive polyarthritis and extended oligoarthritis). 
 
pJIA I 
 

The safety and efficacy of Humira were assessed in a multicentre, randomised, double-blind, 
parallel − group study in 171 children (4-17 years old) with polyarticular JIA. In the open-label lead in 
phase (OL LI) patients were stratified into two groups, MTX (methotrexate)-treated or non-MTX-treated. 
Patients who were in the non-MTX stratum were either naïve to or had been withdrawn from MTX at 
least two weeks prior to study drug administration. Patients remained on stable doses of non-steroidal 
anti-inflammatory drugs (NSAIDs) and or prednisone ( 0.2 mg/kg/day or 10 mg/day maximum). In the 
OL LI phase all patients received 24 mg/m2 up to a maximum of 40 mg Humira every other week for 
16 weeks. The distribution of patients by age and minimum, median and maximum dose received during 
the OL LI phase is presented in Table 17. 
 

Table 17 
Distribution of patients by age and adalimumab dose received during the OL LI phase 

 
Age Group Number of patients at Baseline 

n (%) 
Minimum, median and maximum 
dose

4 to 7 years 31 (18.1) 10, 20 and 25 mg 

8 to 12 years 71 (41.5) 20, 25 and 40 mg 
13 to 17 years 69 (40.4) 25, 40 and 40 mg 

 
Patients demonstrating a Paediatric ACR 30 response at Week 16 were eligible to be randomised into the 
double blind (DB) phase and received either Humira 24 mg/m2 up to a maximum of 40 mg, or placebo 
every other week for an additional 32 weeks or until disease flare. Disease flare criteria were defined as a 
worsening of  30% from baseline in  3 of 6 Paediatric ACR core criteria,  2 active joints, and 
improvement of  30% in no more than 1 of the 6 criteria. After 32 weeks or at disease flare, patients 
were eligible to enrol into the open label extension phase.  
 



35 

Table 18 
Ped ACR 30 Responses in the JIA study 

 
Stratum MTX Without MTX 
Phase  
OL-LI 16 weeks  

Ped ACR 30 
response (n/N) 

94.1% (80/85) 74.4% (64/86) 

                                                           Efficacy Outcomes
Double Blind 32 weeks Humira /MTX 

(N = 38) 
 

Placebo / MTX 
(N = 37) 

Humira  
(N = 30) 

Placebo 
(N = 28) 

Disease flares at 
the end of 
32 weeksa (n/N)

36.8% (14/38) 64.9% (24/37)b 43.3% (13/30) 71.4% 
(20/28)c 

Median time to 
disease flare 

>32 weeks 20 weeks >32 weeks 14 weeks 

 

a Ped ACR 30/50/70 responses Week 48 significantly greater than those of placebo treated patients  
b p = 0.015 
c p = 0.031 
 

Amongst those who responded at Week 16 (n=144), the Paediatric ACR 30/50/70/90 responses were 
maintained for up to six years in the OLE phase in patients who received Humira throughout the study. 
Over all 19 subjects, of which 11 of the baseline age group 4 to 12 and 8 of the baseline age group 13 to 
17 years were treated 6 years or longer. 
 
Overall responses were generally better and, fewer patients developed antibodies when treated with the 
combination of Humira and MTX compared to Humira alone. Taking these results into consideration, 
Humira is recommended for use in combination with MTX and for use as monotherapy in patients for 
whom MTX use is not appropriate (see section 4.2). 
 
pJIA II 
 
The safety and efficacy of Humira was assessed in an open-label, multicentre study in 32 children 
(2 - < 4 years old or aged 4 and above weighing < 15 kg) with moderately to severely active polyarticular 
JIA. The patients received 24 mg/m2 body surface area (BSA) of Humira up to a maximum of 20 mg 
every other week as a single dose via SC injection for at least 24 weeks. During the study, most subjects 
used concomitant MTX, with fewer reporting use of corticosteroids or NSAIDs. 
 
At Week 12 and Week 24, PedACR30 response was 93.5% and 90.0%, respectively, using the observed 
data approach. The proportions of subjects with PedACR50/70/90 at Week 12 and Week 24 were 
90.3%/61.3%/38.7% and 83.3%/73.3%/36.7%, respectively. Amongst those who responded (Paediatric 
ACR 30) at Week 24 (n=27 out of 30 patients), the Paediatric ACR 30 responses were maintained for up 
to 60 weeks in the OLE phase in patients who received Humira throughout this time period. Overall, 
20 subjects were treated for 60 weeks or longer. 
 
Enthesitis-related arthritis 
 
The safety and efficacy of Humira were assessed in a multicentre, randomised, double-blind study in 46 
paediatric patients (6 to 17 years old) with moderate enthesitis-related arthritis. Patients were randomised 
to receive either 24 mg/m2 body surface area (BSA) of Humira up to a maximum of 40 mg, or placebo 
every other week for 12 weeks. The double-blind period is followed by an open-label (OL) period during 



36 

which patients received 24 mg/m2 BSA of Humira up to a maximum of 40 mg every other week 
subcutaneously for up to an additional 192 weeks. The primary endpoint was the percent change from 
Baseline to Week 12 in the number of active joints with arthritis (swelling not due to deformity or joints 
with loss of motion plus pain and/or tenderness), which was achieved with mean percent decrease of -
62.6% (median percent change -88.9%) in patients in the Humira group compared to -11.6% (median 
percent change -50.0%) in patients in the placebo group. Improvement in number of active joints with 
arthritis was maintained during the OL period through Week 156 for the 26 of 31 (84%) patients in the 
Humira group who remained in the study. Although not statistically significant, the majority of patients 
demonstrated clinical improvement in secondary endpoints such as number of sites of enthesitis, tender 
joint count (TJC), swollen joint count (SJC), Paediatric ACR 50 response, and Paediatric ACR 70 
response. 
 
Paediatric plaque psoriasis  

 

The efficacy of Humira was assessed in a randomised, double-blind, controlled study of 114 paediatric 
patients from 4 years of age with severe chronic plaque psoriasis (as defined by a Physician’s Global 
Assessment (PGA) ≥ 4 or >  20% BSA involvement or > 10% BSA involvement with very thick lesions or 
Psoriasis Area and Severity Index (PASI) ≥ 20 or ≥ 10 with clinically relevant facial, genital, or hand/ foot 
involvement) who were inadequately controlled with topical therapy and heliotherapy or phototherapy.  
 
Patients received Humira 0.8 mg/kg eow (up to 40 mg), 0.4 mg/kg eow (up to 20 mg), or methotrexate 
0.1-0.4 mg/kg weekly (up to 25 mg). At Week 16, more patients randomised to Humira 0.8 mg/kg had 
positive efficacy responses (e.g., PASI 75) than those randomised to 0.4 mg/kg eow or MTX.   
 

Table 19:  Paediatric Plaque Psoriasis Efficacy Results at 16 Weeks 
 

 
MTXa 
N=37 

Humira 0.8 mg/kg eow 
N=38  

 PASI 75b 12 (32.4%) 22 (57.9%) 
 PGA: Clear/minimalc 15 (40.5%) 23 (60.5%) 
a MTX = methotrexate 
b P=0.027, Humira 0.8 mg/kg versus MTX 
c P=0.083, Humira 0.8 mg/kg versus MTX
 

Patients who achieved PASI 75 and PGA clear or minimal were withdrawn from treatment for up to 
36 weeks and monitored for loss of disease control (i.e. a worsening of PGA by at least 2 grades). Patients 
were then re-treated with adalimumab 0.8 mg/kg eow for an additional 16 weeks and response rates 
observed during retreatment were similar to the previous double-blind period: PASI 75 response of 78.9% 
(15 of 19 subjects) and PGA clear or minimal of 52.6% (10 of 19 subjects). 
 
In the open label period of the study, PASI 75 and PGA clear or minimal responses were maintained for 
up to an additional 52 weeks with no new safety findings. 
 
Paediatric Crohn’s disease  
 

Humira was assessed in a multicentre, randomised, double-blind clinical trial designed to evaluate the 
efficacy and safety of induction and maintenance treatment with doses dependent on body weight (< 40 kg 
or ≥ 40 kg) in 192 paediatric subjects between the ages of 6 and 17 (inclusive) years, with moderate to 
severe Crohn´s disease (CD) defined as Paediatric Crohn's Disease Activity Index (PCDAI) score > 30. 
Subjects had to have failed conventional therapy (including a corticosteroid and/or an immunomodulator) 
for CD. Subjects may also have previously lost response or been intolerant to infliximab.  
 



37 

All subjects received open-label induction therapy at a dose based on their Baseline body weight: 160 mg 
at Week 0 and 80 mg at Week 2 for subjects ≥ 40 kg, and 80 mg and 40 mg, respectively, for subjects 
< 40 kg. 
 
At Week 4, subjects were randomised 1:1 based on their body weight at the time to either the Low Dose or 
Standard Dose maintenance regimens as shown in Table 20. 
 

Table 20 
Maintenance regimen

Patient 
Weight 

Low dose Standard 
dose 

< 40 kg 10 mg eow 20 mg eow
≥ 40 kg 20 mg eow 40 mg eow

 
Efficacy results 
 
The primary endpoint of the study was clinical remission at Week 26, defined as PCDAI score  10. 
 
Clinical remission and clinical response (defined as reduction in PCDAI score of at least 15 points from 
Baseline) rates are presented in Table 21. Rates of discontinuation of corticosteroids or 
immunomodulators are presented in Table 22. 
 

Table 21 
Paediatric CD Study 

PCDAI Clinical Remission and Response 
 Standard Dose

40/20 mg eow 
N = 93 

Low Dose 
20/10 mg eow 

N = 95 

P value* 

Week 26    
   Clinical remission 38.7% 28.4% 0.075 
   Clinical response  59.1% 48.4% 0.073 
Week 52    
   Clinical remission 33.3% 23.2% 0.100 
   Clinical response 41.9% 28.4% 0.038 
* p value for Standard Dose versus Low Dose comparison.

 
Table 22 

Paediatric CD Study 
Discontinuation of Corticosteroids or Immunomodulators and Fistula Remission 

 Standard Dose
40/20 mg eow  

Low Dose 
20/10 mg eow  

P value1 

Discontinued corticosteroids N= 33 N=38  
Week 26 84.8% 65.8% 0.066 
Week 52 69.7% 60.5% 0.420 
Discontinuation of Immunomodulators2 N=60 N=57  
Week 52 30.0% 29.8% 0.983 
Fistula remission3 N=15 N=21  
Week 26 46.7% 38.1% 0.608 
Week 52 40.0% 23.8% 0.303 
1  p value for Standard Dose versus Low Dose comparison. 
2  Immunosuppressant therapy could only be discontinued at or after Week 26 at the 
investigator's discretion if the subject met the clinical response criterion 



38 

3 defined as a closure of all fistulas that were draining at Baseline for at least 2 consecutive 
post-Baseline visits

 
Statistically significant increases (improvement) from Baseline to Week 26 and 52 in Body Mass Index 
and height velocity were observed for both treatment groups. 
 
Statistically and clinically significant improvements from Baseline were also observed in both treatment 
groups for quality of life parameters (including IMPACT III). 
 
One hundred patients (n=100) from the Paediatric CD Study continued in an open-label long-term 
extension study. After 5 years of adalimumab therapy, 74.0% (37/50) of the 50 patients remaining in the 
study continued to be in clinical remission, and 92.0% (46/50) of patients continued to be in clinical 
response per PCDAI. 
 
Paediatric Uveitis  
 
The safety and efficacy of Humira was assessed in a randomized, double-masked, controlled study of 90 
paediatric patients from 2 to < 18 years of age with active JIA-associated noninfectious anterior uveitis 
who were refractory to at least 12 weeks of methotrexate treatment. Patients received either placebo or 
20 mg adalimumab (if < 30 kg) or 40 mg adalimumab (if ≥ 30 kg) every other week in combination with 
their baseline dose of methotrexate.  
 
The primary endpoint was ‘time to treatment failure’. The criteria determining treatment failure were 
worsening or sustained non-improvement in ocular inflammation, partial improvement with development 
of sustained ocular co-morbidities or worsening of ocular co-morbidities, non-permitted use of 
concomitant medications, and suspension of treatment for an extended period of time. 
 
Clinical Response 
 
Adalimumab significantly delayed the time to treatment failure, as compared to placebo (See Figure 2, 
P < 0.0001 from log rank test).The median time to treatment failure was 24.1 weeks for subjects treated 
with placebo, whereas the median time to treatment failure was not estimable for subjects treated with 
adalimumab because less than one-half of these subjects experienced treatment failure. Adalimumab 
significantly decreased the risk of treatment failure by 75% relative to placebo, as shown by the hazard 
ratio (HR = 0.25 [95% CI: 0.12, 0.49]). 



39 

 
Figure 2: Kaplan-Meier Curves Summarizing Time to Treatment Failure in the Paediatric Uveitis 
Study 

 

P
R

O
B

A
B

IL
IT

Y
 O

F
 F

A
IL

IN
G

 T
R

E
A

T
M

E
N

T
 

 TIME (WEEKS) 
 Treatment Placebo  Adalimumab 
 Note: P = Placebo (Number at Risk); H = HUMIRA (Number at Risk).

 
 
5.2 Pharmacokinetic properties 
 
Absorption and distribution 
 
Following the administration of 24 mg/m2 (maximum of 40 mg) subcutaneously every other week to 
patients with polyarticular juvenile idiopathic arthritis (JIA) who were 4 to 17 years the mean trough 
steady-state (values measured from Week 20 to 48) serum adalimumab concentration was 5.6 ± 5.6 µg/ml 
(102% CV) for adalimumab without concomitant methotrexate and 10.9 ± 5.2 µg/ml (47.7% CV) with 
concomitant methotrexate. 
 
In patients with polyarticular JIA who were 2 to < 4 years old or aged 4 and above weighing < 15 kg 
dosed with adalimumab 24 mg/m2 , the mean trough steady-state serum adalimumab concentrations was 
6.0 ± 6.1 µg/ml (101% CV) for adalimumab without concomitant methotrexate and 7.9 ± 5.6 µg/ml 
(71.2% CV) with concomitant methotrexate. 
 



40 

Following the administration of 24 mg/m2 (maximum of 40 mg) subcutaneously every other week to 
patients with enthesitis-related arthritis who were 6 to 17 years, the mean trough steady-state (values 
measured at Week 24) serum adalimumab concentrations were 8.8 ± 6.6 μg/ml for adalimumab without 
concomitant methotrexate and 11.8 ± 4.3 μg/ml with concomitant methotrexate. 
 
Following the administration of 0.8 mg/kg (maximum of 40 mg) subcutaneously every other week to 
paediatric patients with chronic plaque psoriasis, the mean ± SD steady-state adalimumab trough 
concentration was approximately 7.4 ± 5.8 µg/ml (79% CV). 
 
In paediatric patients with moderate to severe CD, the open-label adalimumab induction dose was 
160/80 mg or 80/40 mg at Weeks 0 and 2, respectively, dependent on a body weight cut-off of 40 kg. At 
Week 4, patients were randomised 1:1 to either the Standard Dose (40/20 mg eow) or Low Dose 
(20/10 mg eow) maintenance treatment groups based on their body weight. The mean (±SD) serum 
adalimumab trough concentrations achieved at Week 4 were 15.7 ± 6.6 g/ml for patients ≥ 40 kg 
(160/80 mg) and 10.6 ± 6.1 g/ml for patients < 40 kg (80/40 mg).  
 
For patients who stayed on their randomised therapy, the mean (±SD) adalimumab trough concentrations 
at Week 52 were 9.5 ± 5.6 g/ml for the Standard Dose group and 3.5 ± 2.2 g/ml for the Low Dose 
group. The mean trough concentrations were maintained in patients who continued to receive adalimumab 
treatment eow for 52 weeks. For patients who dose escalated from eow to weekly regimen, the mean 
(±SD) serum concentrations of adalimumab at Week 52 were 15.3 ± 11.4 μg/ml (40/20 mg, weekly) and 
6.7 ± 3.5 μg/ml (20/10 mg, weekly).  
 
Adalimumab exposure in paediatric uveitis patients was predicted using population pharmacokinetic 
modelling and simulation based on cross-indication pharmacokinetics in other paediatric patients 
(paediatric psoriasis, juvenile idiopathic arthritis, paediatric Crohn’s disease, and enthesitis-related 
arthritis). No clinical exposure data are available on the use of a loading dose in children < 6 years. The 
predicted exposures indicate that in the absence of methotrexate, a loading dose may lead to an initial 
increase in systemic exposure. 
 
Exposure-response relationship in paediatric population 
On the basis of clinical trial data in patients with JIA (pJIA and ERA), an exposure-response relationship 
was established between plasma concentrations and PedACR 50 response. The apparent adalimumab 
plasma concentration that produces half the maximum probability of PedACR 50 response (EC50) was 
3 μg/ml (95% CI: 1-6 μg/ml).  
 
Exposure-response relationships between adalimumab concentration and efficacy in paediatric patients 
with severe chronic plaque psoriasis were established for PASI 75 and PGA clear or minimal, 
respectively. PASI 75 and PGA clear or minimal increased with increasing adalimumab concentrations, 
both with a similar apparent EC50 of approximately 4.5 μg/ml (95% CI 0.4-47.6 and 1.9-10.5, 
respectively). 
 
Adults 
 
After subcutaneous administration of a single 40 mg dose, absorption and distribution of adalimumab was 
slow, with peak serum concentrations being reached about 5 days after administration. The average 
absolute bioavailability of adalimumab estimated from three studies following a single 40 mg 
subcutaneous dose was 64%. After single intravenous doses ranging from 0.25 to 10 mg/kg, 
concentrations were dose proportional. After doses of 0.5 mg/kg (~40 mg), clearances ranged from 11 to 
15 ml/hour, the distribution volume (Vss) ranged from 5 to 6 litres and the mean terminal phase half-life 
was approximately two weeks. Adalimumab concentrations in the synovial fluid from several rheumatoid 
arthritis patients ranged from 31-96% of those in serum. 
 



41 

Following subcutaneous administration of 40 mg of adalimumab every other week in adult rheumatoid 
arthritis (RA) patients the mean steady-state trough concentrations were approximately 5 g/ml (without 
concomitant methotrexate) and 8 to 9 g/ml (with concomitant methotrexate), respectively. The serum 
adalimumab trough levels at steady-state increased roughly proportionally with dose following 20, 40 and 
80 mg subcutaneous dosing every other week and every week. 
 
In adult patients with psoriasis, the mean steady-state trough concentration was 5 g/ml during 
adalimumab 40 mg every other week monotherapy treatment. 
 
In patients with Crohn’s disease, the loading dose of 80 mg Humira on Week 0 followed by 40 mg Humira 
on Week 2 achieves serum adalimumab trough concentrations of approximately 5.5 g/ml during the 
induction period. A loading dose of 160 mg Humira on Week 0 followed by 80 mg Humira on Week 2 
achieves serum adalimumab trough concentrations of approximately 12 g/ml during the induction period. 
Mean steady-state trough levels of approximately 7 g/ml were observed in Crohn’s disease patients who 
received a maintenance dose of 40 mg Humira every other week. 
 
In adult patients with uveitis, a loading dose of 80 mg adalimumab on Week 0 followed by 40 mg 
adalimumab every other week starting at Week 1, resulted in mean steady-state concentrations of 
approximately 8 to 10 g/ml. 
 
Population pharmacokinetic and pharmacokinetic/pharmacodynamic modelling and simulation predicted 
comparable adalimumab exposure and efficacy in patients treated with 80 mg every other week when 
compared with 40 mg every week (including adult patients with RA, HS, UC, CD or Ps, patients with 
adolescent HS, and paediatric patients ≥ 40 kg with CD). 
 
Elimination 
 
Population pharmacokinetic analyses with data from over 1,300 RA patients revealed a trend toward 
higher apparent clearance of adalimumab with increasing body weight. After adjustment for weight 
differences, gender and age appeared to have a minimal effect on adalimumab clearance. The serum levels 
of free adalimumab (not bound to anti-adalimumab antibodies, AAA) were observed to be lower in 
patients with measurable AAA. 
 
Hepatic or renal impairment 
 
Humira has not been studied in patients with hepatic or renal impairment. 
 
5.3 Preclinical safety data  
 
Non-clinical data reveal no special hazard for humans based on studies of single dose toxicity, repeated 
dose toxicity, and genotoxicity.   
 
An embryo-foetal developmental toxicity/perinatal developmental study has been performed in 
cynomolgus monkeys at 0, 30 and 100 mg/kg (9-17 monkeys/group) and has revealed no evidence of harm 
to the foetuses due to adalimumab. Neither carcinogenicity studies, nor a standard assessment of fertility 
and postnatal toxicity, were performed with adalimumab due to the lack of appropriate models for an 
antibody with limited cross-reactivity to rodent TNF and to the development of neutralising antibodies in 
rodents.  
 
 



42 

6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients  
 
Mannitol 
Polysorbate 80 
Water for injections 
 
6.2 Incompatibilities  
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life  
 
2 years 
 
6.4 Special precautions for storage  
 
Store in a refrigerator (2C – 8C). Do not freeze. Keep the pre-filled syringe in its outer carton in order to 
protect from light.   
 
A single Humira pre-filled syringe may be stored at temperatures up to a maximum of 25°C for a period of 
up to 14 days. The syringe must be protected from light, and discarded if not used within the 14-day 
period. 
 
6.5 Nature and contents of container    
 
Humira 20 mg solution for injection in single-use pre-filled syringe (type I glass) with a plunger stopper 
(bromobutyl rubber) and a needle with a needle shield (thermoplastic elastomer).  
 
Packs of: 
 2 pre-filled syringes (0.2 ml sterile solution), each with 1 alcohol pad, in a blister.  
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER  
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
8. MARKETING AUTHORISATION NUMBERS  
 
EU/1/03/256/022 



43 

 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 08 September 2003 
Date of latest renewal: 08 September 2008  
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 
  



44 

1. NAME OF THE MEDICINAL PRODUCT  
 
Humira 40 mg/0.8 ml solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION  
 
Each 0.8 ml single dose vial contains 40 mg of adalimumab.  
 
Adalimumab is a recombinant human monoclonal antibody produced in Chinese Hamster Ovary cells. 
 
For the full list of excipients, see section 6.1.  
 
 
3. PHARMACEUTICAL FORM  
 
Solution for injection. (injection) 
 
Clear, colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications  
 
Juvenile idiopathic arthritis 
 
Polyarticular juvenile idiopathic arthritis 
 
Humira in combination with methotrexate is indicated for the treatment of active polyarticular juvenile 
idiopathic arthritis, in patients from the age of 2 years who have had an inadequate response to one or 
more disease-modifying anti-rheumatic drugs (DMARDs). Humira can be given as monotherapy in case 
of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate (for the 
efficacy in monotherapy see section 5.1). Humira has not been studied in patients aged less than 2 years.  
 
Enthesitis-related arthritis 
 
Humira is indicated for the treatment of active enthesitis-related arthritis in patients, 6 years of age and 
older, who have had an inadequate response to, or who are intolerant of, conventional therapy (see section 
5.1). 
 
Paediatric plaque psoriasis 
 
Humira is indicated for the treatment of severe chronic plaque psoriasis in children and adolescents from 
4 years of age who have had an inadequate response to or are inappropriate candidates for topical therapy 
and phototherapies. 
 



45 

Adolescent hidradenitis suppurativa 
 
Humira is indicated for the treatment of active moderate to severe hidradenitis suppurativa (acne inversa) 
in adolescents from 12 years of age with an inadequate response to conventional systemic HS therapy (see 
sections 5.1 and 5.2). 
 
Paediatric Crohn's disease  
 
Humira is indicated for the treatment of moderately to severely active Crohn's disease in paediatric 
patients (from 6 years of age) who have had an inadequate response to conventional therapy including 
primary nutrition therapy and a corticosteroid and/or an immunomodulator, or who are intolerant to or 
have contraindications for such therapies. 
 
Paediatric ulcerative colitis 
 
Humira is indicated for the treatment of moderately to severely active ulcerative colitis in paediatric 
patients (from 6 years of age) who have had an inadequate response to conventional therapy including 
corticosteroids and/or 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have 
medical contraindications for such therapies. 
 
Paediatric Uveitis 
 
Humira is indicated for the treatment of paediatric chronic non-infectious anterior uveitis in patients from 
2 years of age who have had an inadequate response to or are intolerant to conventional therapy, or in 
whom conventional therapy is inappropriate. 
 
4.2 Posology and method of administration   
 
Humira treatment should be initiated and supervised by specialist physicians experienced in the diagnosis 
and treatment of conditions for which Humira is indicated. Ophthalmologists are advised to consult with 
an appropriate specialist before initiation of treatment with Humira (see section 4.4). Patients treated with 
Humira should be given the Patient Reminder Card. 
 
After proper training in injection technique, patients may self-inject with Humira if their physician 
determines that it is appropriate and with medical follow-up as necessary.  
 
During treatment with Humira, other concomitant therapies (e.g., corticosteroids and/or 
immunomodulatory agents) should be optimised. 
 
Posology 
 
Paediatric population 
 
Juvenile idiopathic arthritis 
 
Polyarticular juvenile idiopathic arthritis from 2 years of age 
 
The recommended dose of Humira for patients with polyarticular juvenile idiopathic arthritis from 2 years 
of age is based on body weight (Table 1). Humira is administered every other week via subcutaneous 
injection. 
 

Table 1. Humira Dose for Patients with Polyarticular Juvenile Idiopathic Arthritis  
 



46 

Patient Weight Dosing Regimen 

10 kg to < 30 kg 20 mg every other week 

≥ 30 kg 40 mg every other week 
 
Available data suggest that clinical response is usually achieved within 12 weeks of treatment. Continued 
therapy should be carefully reconsidered in a patient not responding within this time period.  
 
There is no relevant use of Humira in patients aged less than 2 years for this indication. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Enthesitis-related arthritis 
 
The recommended dose of Humira for patients with enthesitis-related arthritis from 6 years of age is based 
on body weight (Table 2).  Humira is administered every other week via subcutaneous injection. 

 
Table 2. Humira Dose for Patients with Enthesitis-Related Arthritis  

 
Patient Weight Dosing Regimen 

15 kg to < 30 kg 20 mg every other week 

≥ 30 kg 40 mg every other week 
 
Humira has not been studied in patients with enthesitis-related arthritis aged less than 6 years. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Paediatric plaque psoriasis 
 
The recommended Humira dose for patients with plaque psoriasis from 4 to 17 years of age is based on 
body weight (Table 3). Humira is administered via subcutaneous injection. 
 

Table 3. Humira Dose for Paediatric Patients with Plaque Psoriasis  
 

Patient Weight Dosing Regimen 

15 kg to < 30 kg Initial dose of 20 mg, followed by 
20 mg given every other week 

starting one week after the initial 
dose 

≥ 30 kg Initial dose of 40 mg, followed by 
40 mg given every other week 

starting one week after the initial 
dose 

 
Continued therapy beyond 16 weeks should be carefully considered in a patient not responding within this 
time period. 
 
If retreatment with Humira is indicated, the above guidance on dose and treatment duration should be 
followed. 
 



47 

The safety of Humira in paediatric patients with plaque psoriasis has been assessed for a mean of 
13 months. 
 
There is no relevant use of Humira in children aged less than 4 years for this indication. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Adolescent hidradenitis suppurativa (from 12 years of age, weighing at least 30 kg) 
 
There are no clinical trials with Humira in adolescent patients with HS.   
 
The posology of Humira in these patients has been determined from pharmacokinetic modelling and 
simulation (see section 5.2). 
 
The recommended Humira dose is 80 mg at Week 0 followed by 40 mg every other week starting at 
Week 1 via subcutaneous injection.  
 
In adolescent patients with inadequate response to Humira 40 mg every other week, an increase in dosage 
to 40 mg every week or 80 mg every other week may be considered. 
 
Antibiotics may be continued during treatment with Humira if necessary. It is recommended that the 
patient should use a topical antiseptic wash on their HS lesions on a daily basis during treatment with 
Humira.  
 
Continued therapy beyond 12 weeks should be carefully reconsidered in a patient with no improvement 
within this time period.   
 
Should treatment be interrupted, Humira may be re-introduced as appropriate. 
 
The benefit and risk of continued long-term treatment should be periodically evaluated (see adult data in 
section 5.1). 
 
There is no relevant use of Humira in children aged less than 12 years in this indication. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Paediatric Crohn's disease 
 
The recommended dose of Humira for patients with Crohn’s disease from 6 to 17 years of age is based on 
body weight (Table 4). Humira is administered via subcutaneous injection. 
 

Table 4. Humira Dose for Paediatric Patients with Crohn’s disease 
 

Patient 
Weight 

Induction Dose Maintenance 
Dose 

Starting at 
Week 4

< 40 kg  40 mg at week 0 and 20 mg at week 2 
 

20 mg every 
other week 



48 

Patient 
Weight 

Induction Dose Maintenance 
Dose 

Starting at 
Week 4

In case there is a need for a more rapid response to therapy with the 
awareness that the risk for adverse events may be higher with use of the 
higher induction dose, the following dose may be used: 
 80 mg at week 0 and 40 mg at week 2

≥ 40 kg  80 mg at week 0 and 40 mg at week 2 
 

In case there is a need for a more rapid response to therapy with the 
awareness that the risk for adverse events may be higher with use of the 
higher induction dose, the following dose may be used: 
 160 mg at week 0 and 80 mg at week 2

40 mg every 
other week 

 
Patients who experience insufficient response may benefit from an increase in dosage: 
 < 40 kg: 20 mg every week 
 ≥ 40 kg: 40 mg every week or 80 mg every other week 
 
Continued therapy should be carefully considered in a subject not responding by week 12. 
 
There is no relevant use of Humira in children aged less than 6 years for this indication. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Paediatric ulcerative colitis  
 
The recommended dose of Humira for patients from 6 to 17 years of age with ulcerative colitis is based on 
body weight (Table 5). Humira is administered via subcutaneous injection.  
 

Table 5. Humira Dose for Paediatric Patients with Ulcerative Colitis  

Patient Weight Induction Dose 
Maintenance Dose 

Starting at Week 4* 
< 40 kg • 80 mg at Week 0 (given as two 40 

mg injections in one day) and 
• 40 mg at Week 2 (given as one 40 

mg injection)

• 40 mg every other week 

≥ 40 kg • 160 mg at Week 0 (given as four 
40 mg injections in one day or 
two 40 mg injections per day for 
two consecutive days) and 

• 80 mg at Week 2 (given as two 40 
mg injections in one day)

• 80 mg every other week 

* Paediatric patients who turn 18 years of age while on Humira should continue their prescribed 
maintenance dose. 

  

Continued therapy beyond 8 weeks should be carefully considered in patients not showing signs of 
response within this time period. 
 



49 

There is no relevant use of Humira in children aged less than 6 years in this indication. 
 
Humira may be available in different strengths and/or presentations depending on the individual treatment 
needs.  
 
Paediatric Uveitis  
 
The recommended dose of Humira for paediatric patients with uveitis from 2 years of age is based on 
body weight (Table 6). Humira is administered via subcutaneous injection. 
 
In paediatric uveitis, there is no experience in the treatment with Humira without concomitant treatment 
with methotrexate. 
 

Table 6. Humira Dose for Paediatric Patients with Uveitis 
 

Patient Weight Dosing Regimen 

< 30 kg 20 mg every other week in 
combination with methotrexate 

≥ 30 kg 40 mg every other week in 
combination with methotrexate 

 
When Humira therapy is initiated, a loading dose of 40 mg for patients < 30 kg or 80 mg for patients ≥ 30 
kg may be administered one week prior to the start of maintenance therapy. No clinical data are available 
on the use of a Humira loading dose in children < 6 years of age (see section 5.2). 
 
There is no relevant use of Humira in children aged less than 2 years in this indication.  
 
It is recommended that the benefit and risk of continued long-term treatment should be evaluated on a 
yearly basis (see section 5.1). 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Renal and/or hepatic impairment 
 
Humira has not been studied in these patient populations. No dose recommendations can be made. 
 
Method of administration 
 
Humira is administered by subcutaneous injection. Full instructions for use are provided in the package 
leaflet. 
 
Humira is available in other strengths and presentations. 
 
4.3 Contraindications  
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  
 
Active tuberculosis or other severe infections such as sepsis, and opportunistic infections (see section 4.4). 
 
Moderate to severe heart failure (NYHA class III/IV) (see section 4.4). 
 



50 

4.4 Special warnings and precautions for use   
 
Traceability 
 
In order to improve traceability of biological medicinal products, the name and the batch number of the 
administered product should be clearly recorded. 
 
Infections 
 
Patients taking TNF-antagonists are more susceptible to serious infections. Impaired lung function may 
increase the risk for developing infections. Patients must therefore be monitored closely for infections, 
including tuberculosis, before, during and after treatment with Humira. Because the elimination of 
adalimumab may take up to four months, monitoring should be continued throughout this period. 
 
Treatment with Humira should not be initiated in patients with active infections including chronic or 
localised infections until infections are controlled. In patients who have been exposed to tuberculosis and 
patients who have travelled in areas of high risk of tuberculosis or endemic mycoses, such as 
histoplasmosis, coccidioidomycosis, or blastomycosis, the risk and benefits of treatment with Humira 
should be considered prior to initiating therapy (see Other opportunistic infections). 
 
Patients who develop a new infection while undergoing treatment with Humira should be monitored 
closely and undergo a complete diagnostic evaluation. Administration of Humira should be discontinued if 
a patient develops a new serious infection or sepsis, and appropriate antimicrobial or antifungal therapy 
should be initiated until the infection is controlled. Physicians should exercise caution when considering 
the use of Humira in patients with a history of recurring infection or with underlying conditions which 
may predispose patients to infections, including the use of concomitant immunosuppressive medications. 
 
Serious infections 
 
Serious infections, including sepsis, due to bacterial, mycobacterial, invasive fungal, parasitic, viral, or 
other opportunistic infections such as listeriosis, legionellosis and pneumocystis have been reported in 
patients receiving Humira.   
 
Other serious infections seen in clinical trials include pneumonia, pyelonephritis, septic arthritis and 
septicaemia. Hospitalisation or fatal outcomes associated with infections have been reported.  
 
Tuberculosis 
 
Tuberculosis, including reactivation and new onset of tuberculosis, has been reported in patients receiving 
Humira. Reports included cases of pulmonary and extra-pulmonary (i.e. disseminated) tuberculosis.  
 
Before initiation of therapy with Humira, all patients must be evaluated for both active or inactive 
(“latent”) tuberculosis infection. This evaluation should include a detailed medical assessment of patient 
history of tuberculosis or possible previous exposure to people with active tuberculosis and previous 
and/or current immunosuppressive therapy. Appropriate screening tests (i.e. tuberculin skin test and chest 
X-ray) should be performed in all patients (local recommendations may apply). It is recommended that the 
conduct and results of these tests are recorded in the Patient Reminder Card. Prescribers are reminded of 
the risk of false negative tuberculin skin test results, especially in patients who are severely ill or 
immunocompromised.  
 
If active tuberculosis is diagnosed, Humira therapy must not be initiated (see section 4.3).  
 
In all situations described below, the benefit/risk balance of therapy should be very carefully considered. 



51 

 
If latent tuberculosis is suspected, a physician with expertise in the treatment of tuberculosis should be 
consulted.   
 
If latent tuberculosis is diagnosed, appropriate treatment must be started with anti-tuberculosis prophylaxis 
treatment before the initiation of Humira, and in accordance with local recommendations.  
 
Use of anti-tuberculosis prophylaxis treatment should also be considered before the initiation of Humira in 
patients with several or significant risk factors for tuberculosis despite a negative test for tuberculosis and 
in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment 
cannot be confirmed.   
 
Despite prophylactic treatment for tuberculosis, cases of reactivated tuberculosis have occurred in patients 
treated with Humira. Some patients who have been successfully treated for active tuberculosis have 
redeveloped tuberculosis while being treated with Humira. 
 
Patients should be instructed to seek medical advice if signs/symptoms suggestive of a tuberculosis 
infection (e.g., persistent cough, wasting/weight loss, low grade fever, listlessness) occur during or after 
therapy with Humira.  
 
Other opportunistic infections 
 
Opportunistic infections, including invasive fungal infections have been observed in patients receiving 
Humira. These infections have not consistently been recognised in patients taking TNF-antagonists and 
this has resulted in delays in appropriate treatment, sometimes resulting in fatal outcomes.  
 
For patients who develop the signs and symptoms such as fever, malaise, weight loss, sweats, cough, 
dyspnoea, and/or pulmonary infiltrates or other serious systemic illness with or without concomitant shock 
an invasive fungal infection should be suspected and administration of Humira should be promptly 
discontinued. Diagnosis and administration of empiric antifungal therapy in these patients should be made 
in consultation with a physician with expertise in the care of patients with invasive fungal infections. 
 
Hepatitis B reactivation 
 
Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including Humira, who are 
chronic carriers of this virus (i.e. surface antigen positive). Some cases have had a fatal outcome. Patients 
should be tested for HBV infection before initiating treatment with Humira. For patients who test positive 
for hepatitis B infection, consultation with a physician with expertise in the treatment of hepatitis B is 
recommended. 
 
Carriers of HBV who require treatment with Humira should be closely monitored for signs and symptoms 
of active HBV infection throughout therapy and for several months following termination of therapy. 
Adequate data from treating patients who are carriers of HBV with anti-viral therapy in conjunction with 
TNF-antagonist therapy to prevent HBV reactivation are not available. In patients who develop HBV 
reactivation, Humira should be stopped and effective anti-viral therapy with appropriate supportive 
treatment should be initiated.  
 
Neurological events  
 
TNF-antagonists including Humira have been associated in rare instances with new onset or exacerbation 
of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease 
including multiple sclerosis and optic neuritis, and peripheral demyelinating disease, including Guillain-
Barré syndrome. Prescribers should exercise caution in considering the use of Humira in patients with pre-



52 

existing or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of 
Humira should be considered if any of these disorders develop. There is a known association between 
intermediate uveitis and central demyelinating disorders. Neurologic evaluation should be performed in 
patients with non-infectious intermediate uveitis prior to the initiation of Humira therapy and regularly 
during treatment to assess for pre-existing or developing central demyelinating disorders.  
 
Allergic reactions 
 
Serious allergic reactions associated with Humira were rare during clinical trials. Non-serious allergic 
reactions associated with Humira were uncommon during clinical trials. Reports of serious allergic 
reactions including anaphylaxis have been received following Humira administration. If an anaphylactic 
reaction or other serious allergic reaction occurs, administration of Humira should be discontinued 
immediately and appropriate therapy initiated. 
 
Immunosuppression 
 
In a study of 64 patients with rheumatoid arthritis that were treated with Humira, there was no evidence of 
depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or change in 
enumeration of effector T-, B-, NK-cells, monocyte/macrophages, and neutrophils. 
 
Malignancies and lymphoproliferative disorders 
 
In the controlled portions of clinical trials of TNF-antagonists, more cases of malignancies including 
lymphoma have been observed among patients receiving a TNF-antagonist compared with control 
patients. However, the occurrence was rare. In the post marketing setting, cases of leukaemia have been 
reported in patients treated with a TNF-antagonist. There is an increased background risk for lymphoma 
and leukaemia in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, 
which complicates the risk estimation. With the current knowledge, a possible risk for the development of 
lymphomas, leukaemia, and other malignancies in patients treated with a TNF-antagonist cannot be 
excluded. 
 
Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 
22 years of age) treated with TNF-antagonists (initiation of therapy ≤ 18 years of age), including 
adalimumab in the post marketing setting. Approximately half the cases were lymphomas. The other cases 
represented a variety of different malignancies and included rare malignancies usually associated with 
immunosuppression. A risk for the development of malignancies in children and adolescents treated with 
TNF-antagonists cannot be excluded.  
 
Rare postmarketing cases of hepatosplenic T-cell lymphoma have been identified in patients treated with 
adalimumab. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. 
Some of these hepatosplenic T-cell lymphomas with Humira have occurred in young adult patients on 
concomitant treatment with azathioprine or 6-mercaptopurine used for inflammatory bowel disease. The 
potential risk with the combination of azathioprine or 6-mercaptopurine and Humira should be carefully 
considered. A risk for the development of hepatosplenic T-cell lymphoma in patients treated with Humira 
cannot be excluded (see section 4.8). 
 
No studies have been conducted that include patients with a history of malignancy or in whom treatment 
with Humira is continued following development of malignancy. Thus, additional caution should be 
exercised in considering Humira treatment of these patients (see section 4.8). 
 
All patients, and in particular patients with a medical history of extensive immunosuppressant therapy or 
psoriasis patients with a history of PUVA treatment should be examined for the presence of non-
melanoma skin cancer prior to and during treatment with Humira. Melanoma and Merkel cell carcinoma 



53 

have also been reported in patients treated with TNF-antagonists including adalimumab (see section 4.8). 
 
In an exploratory clinical trial evaluating the use of another TNF-antagonist, infliximab, in patients with 
moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, mostly in the lung 
or head and neck, were reported in infliximab-treated patients compared with control patients. All patients 
had a history of heavy smoking. Therefore, caution should be exercised when using any TNF-antagonist in 
COPD patients, as well as in patients with increased risk for malignancy due to heavy smoking. 
 
With current data it is not known if adalimumab treatment influences the risk for developing dysplasia or 
colon cancer. All patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma 
(for example, patients with long-standing ulcerative colitis or primary sclerosing cholangitis), or who had 
a prior history of dysplasia or colon carcinoma should be screened for dysplasia at regular intervals before 
therapy and throughout their disease course. This evaluation should include colonoscopy and biopsies per 
local recommendations. 
 
Haematologic reactions 
 
Rare reports of pancytopenia including aplastic anaemia have been reported with TNF-antagonists. 
Adverse events of the haematologic system, including medically significant cytopenia (e.g. 
thrombocytopenia, leukopenia) have been reported with Humira. All patients should be advised to seek 
immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias (e.g. 
persistent fever, bruising, bleeding, pallor) while on Humira. Discontinuation of Humira therapy should be 
considered in patients with confirmed significant haematologic abnormalities. 
 
Vaccinations 
 
Similar antibody responses to the standard 23-valent pneumococcal vaccine and the influenza trivalent 
virus vaccination were observed in a study in 226 adult subjects with rheumatoid arthritis who were 
treated with adalimumab or placebo. No data are available on the secondary transmission of infection by 
live vaccines in patients receiving Humira.   
 
It is recommended that paediatric patients, if possible, be brought up to date with all immunisations in 
agreement with current immunisation guidelines prior to initiating Humira therapy. 
 
Patients on Humira may receive concurrent vaccinations, except for live vaccines. Administration of live 
vaccines (e.g., BCG vaccine) to infants exposed to adalimumab in utero is not recommended for 5 months 
following the mother’s last adalimumab injection during pregnancy. 
 
Congestive heart failure 
 
In a clinical trial with another TNF-antagonist worsening congestive heart failure and increased mortality 
due to congestive heart failure have been observed. Cases of worsening congestive heart failure have also 
been reported in patients receiving Humira. Humira should be used with caution in patients with mild 
heart failure (NYHA class I/II). Humira is contraindicated in moderate to severe heart failure (see section 
4.3). Treatment with Humira must be discontinued in patients who develop new or worsening symptoms 
of congestive heart failure. 
 
Autoimmune processes 
 
Treatment with Humira may result in the formation of autoimmune antibodies. The impact of long-term 
treatment with Humira on the development of autoimmune diseases is unknown. If a patient develops 
symptoms suggestive of a lupus-like syndrome following treatment with Humira and is positive for 



54 

antibodies against double-stranded DNA, further treatment with Humira should not be given (see section 
4.8). 
 
Concurrent administration of biologic DMARDS or TNF-antagonists 
 
Serious infections were seen in clinical studies with concurrent use of anakinra and another 
TNF-antagonist, etanercept, with no added clinical benefit compared to etanercept alone. Because of the 
nature of the adverse events seen with the combination of etanercept and anakinra therapy, similar 
toxicities may also result from the combination of anakinra and other TNF-antagonists. Therefore, the 
combination of adalimumab and anakinra is not recommended. (See section 4.5). 
 
Concomitant administration of adalimumab with other biologic DMARDS (e.g, anakinra and abatacept) or 
other TNF-antagonists is not recommended based upon the possible increased risk for infections, 
including serious infections and other potential pharmacological interactions. (See section 4.5). 
 
Surgery 
 
There is limited safety experience of surgical procedures in patients treated with Humira. The long half-
life of adalimumab should be taken into consideration if a surgical procedure is planned. A patient who 
requires surgery while on Humira should be closely monitored for infections, and appropriate actions 
should be taken. There is limited safety experience in patients undergoing arthroplasty while receiving 
Humira.  
 
Small bowel obstruction 
 
Failure to respond to treatment for Crohn’s disease may indicate the presence of fixed fibrotic stricture 
that may require surgical treatment. Available data suggest that Humira does not worsen or cause 
strictures. 
 
Elderly 
 
The frequency of serious infections among Humira treated subjects over 65 years of age (3.7%) was 
higher than for those under 65 years of age (1.5%). Some of those had a fatal outcome. Particular attention 
regarding the risk for infection should be paid when treating the elderly. 
 
Paediatric population 
 
See Vaccinations above. 
 
Excipients with known effects 
 
This medicinal product contains less than 1 mmol of sodium (23 mg) per 0.8 ml dose, i.e. essentially 
‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
Humira has been studied in rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and psoriatic 
arthritis patients taking Humira as monotherapy and those taking concomitant methotrexate. Antibody 
formation was lower when Humira was given together with methotrexate in comparison with use as 
monotherapy. Administration of Humira without methotrexate resulted in increased formation of 
antibodies, increased clearance and reduced efficacy of adalimumab (see section 5.1).  
 



55 

The combination of Humira and anakinra is not recommended (see section 4.4 “Concurrent administration 
of biologic DMARDS or TNF-antagonists”).  
 
The combination of Humira and abatacept is not recommended (see section 4.4 “Concurrent 
administration of biologic DMARDS or TNF-antagonists”). 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential 
 
Women of childbearing potential should consider the use of adequate contraception to prevent pregnancy 
and continue its use for at least five months after the last Humira treatment. 
 
Pregnancy 
 
A large number (approximately 2100) of prospectively collected pregnancies exposed to adalimumab 
resulting in live birth with known outcomes, including more than 1500 exposed during the first trimester, 
does not indicate an increase in the rate of malformation in the newborn. 
 
In a prospective cohort registry, 257 women with rheumatoid arthritis (RA) or Crohn’s disease (CD) 
treated with adalimumab at least during the first trimester and 120 women with RA or CD not treated with 
adalimumab were enrolled.  The primary endpoint was the birth prevalence of major birth defects. The 
rate of pregnancies ending with at least one live born infant with a major birth defect was 6/69 (8.7%) in 
the adalimumab-treated women with RA and 5/74 (6.8%) in the untreated women with RA (unadjusted 
OR 1.31, 95% CI 0.38-4.52) and 16/152 (10.5%) in the adalimumab-treated women with CD and 3/32 
(9.4%) in the untreated women with CD (unadjusted OR 1.14, 95% CI 0.31-4.16). The adjusted OR 
(accounting for baseline differences) was 1.10 (95% CI 0.45-2.73) with RA and CD combined. There were 
no distinct differences between adalimumab-treated and untreated women for the secondary endpoints 
spontaneous abortions, minor birth defects, preterm delivery, birth size and serious or opportunistic 
infections and no stillbirths or malignancies were reported. The interpretation of data may be impacted due 
to methodological limitations of the study, including small sample size and non-randomized design. 
 
In a developmental toxicity study conducted in monkeys, there was no indication of maternal toxicity, 
embryotoxicity or teratogenicity. Preclinical data on postnatal toxicity of adalimumab are not available 
(see section 5.3). 
 
Due to its inhibition of TNF, adalimumab administered during pregnancy could affect normal immune 
responses in the newborn.  Adalimumab should only be used during pregnancy if clearly needed. 
 
Adalimumab may cross the placenta into the serum of infants born to women treated with adalimumab 
during pregnancy. Consequently, these infants may be at increased risk for infection. Administration of 
live vaccines (e.g., BCG vaccine) to infants exposed to adalimumab in utero is not recommended for 
5 months following the mother’s last adalimumab injection during pregnancy. 
 
Breast-feeding 
 
Limited information from the published literature indicates that adalimumab is excreted in breast milk at 
very low concentrations with the presence of adalimumab in human milk at concentrations of 0.1% to 1% 
of the maternal serum level. Given orally, immunoglobulin G proteins undergo intestinal proteolysis and 
have poor bioavailability. No effects on the breastfed newborns/infants are anticipated. Consequently, 
Humira can be used during breastfeeding. 
 
Fertility 



56 

 
Preclinical data on fertility effects of adalimumab are not available. 
 
4.7 Effects on ability to drive and use machines  
 
Humira may have a minor influence on the ability to drive and use machines. Vertigo and visual 
impairment may occur following administration of Humira (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
 
Humira was studied in 9,506 patients in pivotal controlled and open label trials for up to 60 months or 
more. These trials included rheumatoid arthritis patients with short term and long standing disease, 
juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis) as 
well as axial spondyloarthritis (ankylosing spondylitis and axial spondyloarthritis without radiographic 
evidence of AS), psoriatic arthritis, Crohn’s disease, ulcerative colitis, psoriasis, hidradenitis suppurativa 
and uveitis patients. The pivotal controlled studies involved 6,089 patients receiving Humira and 3,801 
patients receiving placebo or active comparator during the controlled period. 
 
The proportion of patients who discontinued treatment due to adverse events during the double-blind, 
controlled portion of pivotal studies was 5.9% for patients taking Humira and 5.4% for control treated 
patients. 
 
The most commonly reported adverse reactions are infections (such as nasopharyngitis, upper respiratory 
tract infection and sinusitis), injection site reactions (erythema, itching, haemorrhage, pain or swelling), 
headache and musculoskeletal pain. 
 
Serious adverse reactions have been reported for Humira. TNF-antagonists, such as Humira affect the 
immune system and their use may affect the body’s defence against infection and cancer. 
Fatal and life-threatening infections (including sepsis, opportunistic infections and TB), HBV reactivation 
and various malignancies (including leukaemia, lymphoma and HSTCL) have also been reported with use 
of Humira. 
 
Serious haematological, neurological and autoimmune reactions have also been reported. These include 
rare reports of pancytopenia, aplastic anaemia, central and peripheral demyelinating events and reports of 
lupus, lupus-related conditions and Stevens-Johnson syndrome. 
 
Paediatric population 
 
In general, the adverse events in paediatric patients were similar in frequency and type to those seen in 
adult patients. 
 
Tabulated list of adverse reactions 
 
The following list of adverse reactions is based on experience from clinical trials and on postmarketing 
experience and are displayed by system organ class and frequency in Table 7 below: very common 
( 1/10); common ( 1/100 to < 1/10); uncommon ( 1/1,000 to< 1/100); rare ( 1/10,000 to < 1/1,000); 
and not known (cannot be estimated from the available data). Within each frequency grouping, 
undesirable effects are presented in order of decreasing seriousness. The highest frequency seen among the 
various indications has been included. An asterisk (*) appears in the SOC column if further information is 
found elsewhere in sections 4.3, 4.4 and 4.8. 
 



57 

Table 7 
Undesirable Effects 

 

System Organ Class Frequency Adverse Reaction 

Infections and 
infestations* 

 

Very common Respiratory tract infections (including lower and 
upper respiratory tract infection, pneumonia, 
sinusitis, pharyngitis, nasopharyngitis and 
pneumonia herpes viral) 

Common 

 

Systemic infections (including sepsis, candidiasis 
and influenza), 
intestinal infections (including gastroenteritis 
viral), 
skin and soft tissue infections (including 
paronychia, cellulitis, impetigo, necrotising 
fasciitis and herpes zoster), 
ear infections, 
oral infections (including herpes simplex, oral 
herpes and tooth infections),  
reproductive tract infections (including 
vulvovaginal mycotic infection),  

urinary tract infections (including 
pyelonephritis), 

fungal infections, 

joint infections 

Uncommon 
 

Neurological infections (including viral 
meningitis), 
opportunistic infections and tuberculosis 
(including coccidioidomycosis, histoplasmosis 
and mycobacterium avium complex infection),  
bacterial infections, 
eye infections, 
diverticulitis1)  

Neoplasms benign, 
malignant and unspecified 
(including cysts and 
polyps)* 

Common 

 

Skin cancer excluding melanoma (including 
basal cell carcinoma and squamous cell 
carcinoma), 

benign neoplasm 

Uncommon 
 

Lymphoma**,  
solid organ neoplasm (including breast cancer, 
lung neoplasm and thyroid neoplasm), 
melanoma** 

Rare Leukaemia1) 



58 

System Organ Class Frequency Adverse Reaction 

Not known Hepatosplenic T-cell lymphoma1), 

Merkel cell carcinoma (neuroendocrine 
carcinoma of the skin)1), 

Kaposi’s sarcoma 

Blood and the lymphatic 
system disorders* 

Very common 

 

Leukopenia (including neutropenia and 
agranulocytosis),  

anaemia  

 
Common Leucocytosis, 

thrombocytopenia 

Uncommon Idiopathic thrombocytopenic purpura 

Rare 
 

Pancytopenia 

Immune system disorders* Common 

 

Hypersensitivity, 

allergies (including seasonal allergy) 

Uncommon Sarcoidosis1), 

vasculitis 

Rare Anaphylaxis1) 

Metabolism and nutrition 
disorders 

Very common 

 

Lipids increased 

Common 

 

Hypokalaemia,  

uric acid increased,  

blood sodium abnormal, 

hypocalcaemia, 

hyperglycaemia, 

hypophosphatemia, 

dehydration 

Psychiatric disorders Common 

 

Mood alterations (including depression),  

anxiety, 

insomnia 

Nervous system disorders* Very common 

 

Headache 



59 

System Organ Class Frequency Adverse Reaction 

Common 

 

Paraesthesias (including hypoesthesia), 

migraine, 

nerve root compression  

Uncommon 
 

Cerebrovascular accident1), 
tremor, 
neuropathy  

Rare 
 

Multiple sclerosis, 

demyelinating disorders (e.g. optic neuritis, 
Guillain-Barré syndrome) 1) 

Eye disorders Common 

 

Visual impairment, 

conjunctivitis, 

blepharitis, 

eye swelling 

Uncommon Diplopia 

Ear and labyrinth 
disorders  

 

Common 

 

Vertigo 

Uncommon 
 

Deafness,  
tinnitus 

Cardiac disorders*  Common Tachycardia 

Uncommon 

 

Myocardial infarction1), 

arrhythmia, 

congestive heart failure 

Rare 
 

Cardiac arrest 

Vascular disorders Common 

 

Hypertension,  

flushing,  

haematoma 

Uncommon Aortic aneurysm, 
vascular arterial occlusion, 
thrombophlebitis  

Respiratory, thoracic and 
mediastinal disorders* 

Common 

 

Asthma, 

dyspnoea, 

cough 



60 

System Organ Class Frequency Adverse Reaction 

Uncommon 
 

Pulmonary embolism1), 
interstitial lung disease,  
chronic obstructive pulmonary disease, 
pneumonitis, 
pleural effusion1) 

Rare Pulmonary fibrosis1) 

Gastrointestinal disorders Very common 

 

Abdominal pain,  

nausea and vomiting 

Common 
 

GI haemorrhage,  
dyspepsia,  
gastroesophageal reflux disease, 
sicca syndrome 

Uncommon 
 

Pancreatitis,  
dysphagia, 
face oedema 

Rare Intestinal perforation1) 

Hepato-biliary disorders* Very Common 

 

Elevated liver enzymes 

Uncommon 
 

Cholecystitis and cholelithiasis, 
hepatic steatosis,  
bilirubin increased 

Rare 
 

Hepatitis 

reactivation of hepatitis B1)  

autoimmune hepatitis1) 

Not known Liver failure1) 

Skin and subcutaneous 
tissue disorders 

Very Common 

 

Rash (including exfoliative rash) 

Common 
 

Worsening or new onset of psoriasis (including 
palmoplantar pustular psoriasis)1), 
urticaria, 
bruising (including purpura),  
dermatitis (including eczema), 
onychoclasis,  
hyperhidrosis, 
alopecia1), 
pruritus 



61 

System Organ Class Frequency Adverse Reaction 

Uncommon 
 

Night sweats, 
scar 

Rare Erythema multiforme1), 

Stevens-Johnson syndrome1), 

angioedema1), 

cutaneous vasculitis1) 

lichenoid skin reaction1) 

Not known Worsening of symptoms of dermatomyositis1) 

Musculoskeletal and 
connective tissue disorders 

Very common 

 

Musculoskeletal pain 

Common Muscle spasms (including blood creatine 
phosphokinase increased) 

Uncommon Rhabdomyolysis, 
systemic lupus erythematosus 

Rare 
 

Lupus-like syndrome1) 

Renal and urinary 
disorders  

Common 

 

Renal impairment, 

haematuria 

Uncommon 
 

Nocturia 

Reproductive system and 
breast disorders 

Uncommon Erectile dysfunction 

General disorders and 
administration site 
conditions* 

Very Common 

 

Injection site reaction (including injection site 
erythema) 

Common 
 

Chest pain,  
oedema, 
pyrexia1) 

Uncommon 
 

Inflammation 

Investigations* Common Coagulation and bleeding disorders (including 
activated partial thromboplastin time prolonged), 

autoantibody test positive (including double 
stranded DNA antibody),  

blood lactate dehydrogenase increased 

Injury, poisoning and 
procedural complications 

Common Impaired healing 



62 

 
* further information is found elsewhere in sections 4.3, 4.4 and 4.8 
** including open label extension studies 
1) including spontaneous reporting data 
 
Hidradenitis suppurativa 
 
The safety profile for patients with HS treated with Humira weekly was consistent with the known safety 
profile of Humira. 
 
Uveitis 
 
The safety profile for patients with uveitis treated with Humira every other week was consistent with the 
known safety profile of Humira. 
 
Description of selected adverse reactions 
 
Injection site reactions 
 
In the pivotal controlled trials in adults and children, 12.9% of patients treated with Humira developed 
injection site reactions (erythema and/or itching, haemorrhage, pain or swelling), compared to 7.2% of 
patients receiving placebo or active control. Injection site reactions generally did not necessitate 
discontinuation of the medicinal product.  
 
Infections  
 
In the pivotal controlled trials in adults and children, the rate of infection was 1.51 per patient year in the 
Humira treated patients and 1.46 per patient year in the placebo and active control-treated patients. The 
infections consisted primarily of nasopharyngitis, upper respiratory tract infection, and sinusitis. Most 
patients continued on Humira after the infection resolved.   
 
The incidence of serious infections was 0.04 per patient year in Humira treated patients and 0.03 per 
patient year in placebo and active control − treated patients.   
 
In controlled and open label adult and paediatric studies with Humira, serious infections (including fatal 
infections, which occurred rarely) have been reported, which include reports of tuberculosis (including 
miliary and extra-pulmonary locations) and invasive opportunistic infections (e.g. disseminated or 
extrapulmonary histoplasmosis, blastomycosis, coccidioidomycosis, pneumocystis, candidiasis, 
aspergillosis and listeriosis). Most of the cases of tuberculosis occurred within the first eight months after 
initiation of therapy and may reflect recrudescence of latent disease. 
 
Malignancies and lymphoproliferative disorders 
 
No malignancies were observed in 249 paediatric patients with an exposure of 655.6 patient years during 
Humira trials in patients with juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and 
enthesitis-related arthritis). In addition, no malignancies were observed in 192 paediatric patients with an 
exposure of 498.1 patient years during Humira trials in paediatric patients with Crohn’s disease. No 
malignancies were observed in 77 paediatric patients with an exposure of 80.0 patient years during a 
Humira trial in paediatric patients with chronic plaque psoriasis. No malignancies were observed in 93 
paediatric patients with an exposure of 65.3 patient years during a Humira trial in paediatric patients with 
ulcerative colitis. No malignancies were observed in 60 paediatric patients with an exposure of 58.4 
patient years during a Humira trial in paediatric patients with uveitis. 
 



63 

During the controlled portions of pivotal Humira trials in adults of at least 12 weeks in duration in patients 
with moderately to severely active rheumatoid arthritis, ankylosing spondylitis, axial spondyloarthritis 
without radiographic evidence of AS, psoriatic arthritis, psoriasis, hidradenitis suppurativa, Crohn’s 
disease, ulcerative colitis and uveitis, malignancies, other than lymphoma and non-melanoma skin cancer, 
were observed at a rate (95% confidence interval) of 6.8 (4.4, 10.5)  per 1,000 patient-years among 5,291 
Humira treated patients versus a rate of 6.3 (3.4, 11.8) per 1,000 patient-years among 3,444 control 
patients (median duration of treatment was 4.0 months for Humira and 3.8 months for control-treated 
patients). The rate (95% confidence interval) of non-melanoma skin cancers was 8.8 (6.0, 13.0) per 1,000 
patient-years among Humira-treated patients and 3.2 (1.3, 7.6) per 1,000 patient-years among control 
patients. Of these skin cancers, squamous cell carcinomas occurred at rates (95% confidence interval) of 
2.7 (1.4, 5.4) per 1,000 patient-years among Humira-treated patients and 0.6 (0.1, 4.5) per 1,000 patient-
years among control patients. The rate (95% confidence interval) of lymphomas was 0.7 (0.2, 2.7) per 
1,000 patient-years among Humira-treated patients and 0.6 (0.1, 4.5) per 1,000 patient-years among 
control patients. 
 
When combining controlled portions of these trials and ongoing and completed open label extension 
studies with a median duration of approximately 3.3 years including 6,427 patients and over 26,439 
patient-years of therapy, the observed rate of malignancies, other than lymphoma and non-melanoma skin 
cancers is approximately 8.5 per 1,000 patient years. The observed rate of non-melanoma skin cancers is 
approximately 9.6 per 1,000 patient years, and the observed rate of lymphomas is approximately 1.3 per 
1,000 patient years. 
 
In post-marketing experience from January 2003 to December 2010, predominantly in patients with 
rheumatoid arthritis, the reported rate of malignancies is approximately 2.7 per 1,000 patient treatment 
years. The reported rates for non-melanoma skin cancers and lymphomas are approximately 0.2 and 0.3 
per 1,000 patient treatment years, respectively (see section 4.4). 
 
Rare post-marketing cases of hepatosplenic T-cell lymphoma have been reported in patients treated with 
adalimumab (see section 4.4). 
 
Autoantibodies  
 
Patients had serum samples tested for autoantibodies at multiple time points in rheumatoid arthritis studies 
I − V. In these trials, 11.9% of patients treated with Humira and 8.1% of placebo and active 
control − treated patients that had negative baseline anti-nuclear antibody titres reported positive titres at 
Week 24. Two patients out of 3,441 treated with Humira in all rheumatoid arthritis and psoriatic arthritis 
studies developed clinical signs suggestive of new-onset lupus-like syndrome. The patients improved 
following discontinuation of therapy. No patients developed lupus nephritis or central nervous system 
symptoms. 
 
Hepato-biliary events 
 
In controlled Phase 3 trials of Humira in patients with rheumatoid arthritis and psoriatic arthritis with a 
control period duration ranging from 4 to 104 weeks, ALT elevations ≥ 3 x ULN occurred in 3.7% of 
Humira-treated patients and 1.6% of control-treated patients.  
 
In controlled Phase 3 trials of Humira in patients with polyarticular juvenile idiopathic arthritis who were 
4 to 17 years and enthesitis-related arthritis who were 6 to 17 years, ALT elevations ≥ 3 x ULN occurred 
in 6.1% of Humira-treated patients and 1.3% of control-treated patients. Most ALT elevations occurred 
with concomitant methotrexate use. No ALT elevations ≥ 3 x ULN occurred in the Phase 3 trial of Humira 
in patients with polyarticular juvenile idiopathic arthritis who were 2 to <4 years. 
 



64 

In controlled Phase 3 trials of Humira in patients with Crohn’s disease and ulcerative colitis with a control 
period ranging from 4 to 52 weeks. ALT elevations ≥ 3 x ULN occurred in 0.9% of Humira-treated 
patients and 0.9% of controlled-treated patients.  
 
In the Phase 3 trial of Humira in patients with paediatric Crohn’s disease which evaluated efficacy and 
safety of two body weight adjusted maintenance dose regimens following body weight adjusted induction 
therapy up to 52 weeks of treatment, ALT elevations ≥ 3 x ULN occurred in 2.6% (5/192) of patients of 
whom 4 were receiving concomitant immunosuppressants at baseline. 
 
In controlled Phase 3 trials of Humira in patients with plaque psoriasis with a control period duration 
ranging from 12 to 24 weeks, ALT elevations ≥ 3 x ULN occurred in 1.8% of Humira-treated patients and 
1.8% of control-treated patients.  
 
No ALT elevations ≥ 3 X ULN occurred in the Phase 3 trial of Humira in paediatric patients with plaque 
psoriasis. 
 
In controlled trials of Humira (initial doses of 160 mg at Week 0 and 80 mg at Week 2, followed by 40 mg 
every week starting at Week 4), in patients with hidradenitis suppurativa with a control period duration 
ranging from 12 to 16 weeks, ALT elevations ≥ 3 x ULN occurred in 0.3% of Humira-treated patients and 
0.6% of control-treated patients. 
 
In controlled trials of Humira (initial doses of 80 mg at Week 0 followed by 40 mg every other week 
starting at Week 1) in adult patients with uveitis up to 80 weeks with a median exposure of 166.5 days and 
105.0 days in Humira-treated and control-treated patients, respectively, ALT elevations ≥ 3 x ULN 
occurred in 2.4% of Humira-treated patients and 2.4% of control-treated patients.  
In the controlled Phase 3 trial of Humira in patients with paediatric ulcerative colitis (N=93) which 
evaluated efficacy and safety of a maintenance dose of 0.6 mg/kg (maximum of 40 mg) every other week 
(N=31) and a maintenance dose of 0.6 mg/kg (maximum of 40 mg) every Week (N=32), following body 
weight adjusted induction dosing of 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2 (N=63), or an induction dose of 2.4 mg/kg (maximum of 160 mg) 
at Week 0, placebo at Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2 (N=30), ALT elevations ≥ 
3 X ULN occurred in 1.1% (1/93) of patients. 
 
Across all indications in clinical trials patients with raised ALT were asymptomatic and in most cases 
elevations were transient and resolved on continued treatment. However, there have also been post-
marketing reports of liver failure as well as less severe liver disorders that may precede liver failure, such 
as hepatitis including autoimmune hepatitis in patients receiving adalimumab. 
 
Concurrent treatment with azathioprine/6-mercaptopurine 
 
In adult Crohn’s disease studies, higher incidences of malignant and serious infection-related adverse 
events were seen with the combination of Humira and azathioprine/6-mercaptopurine compared with 
Humira alone. 



65 

 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 
continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are 
asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.  
 
4.9 Overdose  
 
No dose-limiting toxicity was observed during clinical trials. The highest dose level evaluated has been 
multiple intravenous doses of 10 mg/kg, which is approximately 15 times the recommended dose.   
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunosuppressants, Tumour Necrosis Factor alpha (TNF-α) inhibitors. 
ATC code: L04AB04 
 
Mechanism of action 
 
Adalimumab binds specifically to TNF and neutralises the biological function of TNF by blocking its 
interaction with the p55 and p75 cell surface TNF receptors.   
 
Adalimumab also modulates biological responses that are induced or regulated by TNF, including changes 
in the levels of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, and ICAM-1 
with an IC50 of 0.1-0.2 nM).  
 
Pharmacodynamic effects  
 
After treatment with Humira, a rapid decrease in levels of acute phase reactants of inflammation 
(C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) and serum cytokines (IL-6) was 
observed, compared to baseline in patients with rheumatoid arthritis. Serum levels of matrix 
metalloproteinases (MMP-1 and MMP-3) that produce tissue remodelling responsible for cartilage 
destruction were also decreased after Humira administration. Patients treated with Humira usually 
experienced improvement in haematological signs of chronic inflammation. 
 
A rapid decrease in CRP levels was also observed in patients with polyarticular juvenile idiopathic 
arthritis, Crohn's disease, ulcerative colitis and hidradenitis suppurativa after treatment with Humira. In 
patients with Crohn’s disease, a reduction of the number of cells expressing inflammatory markers in the 
colon including a significant reduction of expression of TNFα was seen. Endoscopic studies in intestinal 
mucosa have shown evidence of mucosal healing in adalimumab treated patients. 
 
Clinical efficacy and safety 
 
Adults with rheumatoid arthritis 
 
Humira was evaluated in over 3,000 patients in all rheumatoid arthritis clinical trials. The efficacy and 
safety of Humira were assessed in five randomised, double-blind and well-controlled studies. Some 
patients were treated for up to 120 months duration.  
 



66 

RA study I evaluated 271 patients with moderately to severely active rheumatoid arthritis who were  18 
years old, had failed therapy with at least one disease-modifying, anti rheumatic drug and had insufficient 
efficacy with methotrexate at doses of 12.5 to 25 mg (10 mg if methotrexate-intolerant) every week and 
whose methotrexate dose remained constant at 10 to 25 mg every week. Doses of 20, 40 or 80 mg of 
Humira or placebo were given every other week for 24 weeks.  
 
RA study II evaluated 544 patients with moderately to severely active rheumatoid arthritis who were  18 
years old and had failed therapy with at least one disease-modifying, anti-rheumatic drugs. Doses of 20 or 
40 mg of Humira were given by subcutaneous injection every other week with placebo on alternative 
weeks or every week for 26 weeks; placebo was given every week for the same duration. No other 
disease-modifying anti-rheumatic drugs were allowed. 
 
RA study III evaluated 619 patients with moderately to severely active rheumatoid arthritis who were  18 
years old, and who had an ineffective response to methotrexate at doses of 12.5 to 25 mg or have been 
intolerant to 10 mg of methotrexate every week. There were three groups in this study. The first received 
placebo injections every week for 52 weeks. The second received 20 mg of Humira every week for 
52 weeks. The third group received 40 mg of Humira every other week with placebo injections on 
alternate weeks. Upon completion of the first 52 weeks, 457 patients enrolled in an open-label extension 
phase in which 40 mg of Humira/MTX was administered every other week up to 10 years. 
 
RA study IV primarily assessed safety in 636 patients with moderately to severely active rheumatoid 
arthritis who were  18 years old. Patients were permitted to be either disease-modifying, anti-rheumatic 
drug-naïve or to remain on their pre-existing rheumatologic therapy provided that therapy was stable for a 
minimum of 28 days. These therapies include methotrexate, leflunomide, hydroxychloroquine, 
sulfasalazine and/or gold salts. Patients were randomised to 40 mg of Humira or placebo every other week 
for 24 weeks.   
 
RA study V evaluated 799 methotrexate-naïve, adult patients with moderate to severely active early 
rheumatoid arthritis (mean disease duration less than 9 months). This study evaluated the efficacy of 
Humira 40 mg every other week/methotrexate combination therapy, Humira 40 mg every other week 
monotherapy and methotrexate monotherapy in reducing the signs and symptoms and rate of progression 
of joint damage in rheumatoid arthritis for 104 weeks. Upon completion of the first 104 weeks, 497 
patients enrolled in an open-label extension phase in which 40 mg of Humira was administered every 
other week up to 10 years. 
 
The primary end point in RA studies I, II and III and the secondary endpoint in RA study IV was the 
percent of patients who achieved an ACR 20 response at Week 24 or 26. The primary endpoint in RA 
study V was the percent of patients who achieved an ACR 50 response at Week 52. RA studies III and V 
had an additional primary endpoint at 52 weeks of retardation of disease progression (as detected by X-ray 
results). RA study III also had a primary endpoint of changes in quality of life.  
 
ACR response 
 
The percent of Humira-treated patients achieving ACR 20, 50 and 70 responses was consistent across RA 
studies I, II and III. The results for the 40 mg every other week dose are summarised in Table 8.  



67 

 
Table 8 ACR Responses in Placebo-Controlled Trials 

(Percent of Patients) 
 

Response RA Study Ia** RA Study IIa** RA Study IIIa** 
 

 Placebo/ 
MTXc 
n=60 

Humirab/ MTXc

n=63 
Placebo 
n=110 

Humirab 
n=113 

Placebo/ 
MTXc 
n=200 

Humirab/ MTXc

n=207 

ACR 20    
 6 months 13.3% 65.1% 19.1% 46.0% 29.5% 63.3%
 12 months NA NA NA NA 24.0% 58.9%
ACR 50    
 6 months 6.7% 52.4% 8.2% 22.1% 9.5% 39.1%
 12 months NA NA NA NA 9.5% 41.5%
ACR 70    
 6 months 3.3% 23.8% 1.8% 12.4% 2.5% 20.8%
 12 months NA NA NA NA 4.5% 23.2%
a RA  study I at 24 weeks, RA study II at 26 weeks , and RA study III at 24 and 52 weeks 
b 40 mg Humira administered every other week 
c MTX = methotrexate 
**p < 0.01, Humira versus placebo 

 
In RA studies I-IV, all individual components of the ACR response criteria (number of tender and swollen 
joints, physician and patient assessment of disease activity and pain, disability index (HAQ) scores and 
CRP (mg/dl) values) improved at 24 or 26 weeks compared to placebo. In RA study III, these 
improvements were maintained throughout 52 weeks.  
 
In the open-label extension for RA study III, most patients who were ACR responders maintained 
response when followed for up to 10 years. Of 207 patients who were randomised to Humira 40 mg every 
other week, 114 patients continued on Humira 40 mg every other week for 5 years. Among those, 86 
patients (75.4%) had ACR 20 responses; 72 patients (63.2%) had ACR 50 responses; and 41 patients 
(36%) had ACR 70 responses. Of 207 patients, 81 patients continued on Humira 40 mg every other week 
for 10 years. Among those, 64 patients (79.0%) had ACR 20 responses; 56 patients (69.1%) had ACR 50 
responses; and 43 patients (53.1%) had ACR 70 responses. 
 
In RA study IV, the ACR 20 response of patients treated with Humira plus standard of care was 
statistically significantly better than patients treated with placebo plus standard of care (p < 0.001).   
 
In RA studies I-IV, Humira-treated patients achieved statistically significant ACR 20 and 50 responses 
compared to placebo as early as one to two weeks after initiation of treatment. 
 
In RA study V with early rheumatoid arthritis patients who were methotrexate naïve, combination therapy 
with Humira and methotrexate led to faster and significantly greater ACR responses than methotrexate 
monotherapy and Humira monotherapy at Week 52 and responses were sustained at Week 104 (see Table 
9). 



68 

 
Table 9 ACR Responses in RA Study V 

(percent of patients) 
 

Response 
MTX 
n=257 

Humira 
n=274 

Humira/MTX 
n=268 

p-valuea p-valueb p-valuec 

ACR 20  
 Week 52 62.6% 54.4% 72.8% 0.013 < 0.001 0.043
 Week 104 56.0% 49.3% 69.4% 0.002 < 0.001 0.140
ACR 50  
 Week 52 45.9% 41.2% 61.6% < 0.001 < 0.001 0.317
 Week 104 42.8% 36.9% 59.0% < 0.001 < 0.001 0.162
ACR 70  
 Week 52 27.2% 25.9% 45.5% < 0.001 < 0.001 0.656
 Week 104 28.4% 28.1% 46.6% < 0.001 < 0.001 0.864
a p-value is from the pairwise comparison of methotrexate monotherapy and Humira/methotrexate 

combination therapy using the Mann-Whitney U test. 
b p-value is from the pairwise comparison of Humira monotherapy and Humira/methotrexate 

combination therapy using the Mann-Whitney U test 
c p-value is from the pairwise comparison of Humira monotherapy and methotrexate monotherapy using 

the Mann-Whitney U test 
 
In the open-label extension for RA study V, ACR response rates were maintained when followed for up to 
10 years. Of 542 patients who were randomised to Humira 40 mg every other week, 170 patients 
continued on Humira 40 mg every other week for 10 years. Among those, 154 patients (90.6%) had ACR 
20 responses; 127 patients (74.7%) had ACR 50 responses; and 102 patients (60.0%) had ACR 70 
responses. 
 
At Week 52, 42.9% of patients who received Humira/methotrexate combination therapy achieved clinical 
remission (DAS28 (CRP) < 2.6) compared to 20.6% of patients receiving methotrexate monotherapy and 
23.4% of patients receiving Humira monotherapy. Humira/methotrexate combination therapy was 
clinically and statistically superior to methotrexate (p < 0.001) and Humira monotherapy (p < 0.001) in 
achieving a low disease state in patients with recently diagnosed moderate to severe rheumatoid arthritis. 
The response for the two monotherapy arms was similar (p = 0.447). Of 342 subjects originally 
randomized to Humira monotherapy or Humira/methotrexate combination therapy who entered the open-
label extension study, 171 subjects completed 10 years of Humira treatment. Among those, 109 subjects 
(63.7%) were reported to be in remission at 10 years. 
 
Radiographic response 
 
In RA study III, where Humira treated patients had a mean duration of rheumatoid arthritis of 
approximately 11 years, structural joint damage was assessed radiographically and expressed as change in 
modified Total Sharp Score (TSS) and its components, the erosion score and joint space narrowing score. 
Humira/methotrexate patients demonstrated significantly less radiographic progression than patients 
receiving methotrexate alone at 6 and 12 months (see Table 10).  
 
In the open-label extension of RA Study III, the reduction in rate of progression of structural damage is 
maintained for 8 and 10 years in a subset of patients. At 8 years, 81 of 207 patients originally treated with 
40 mg Humira every other week were evaluated radiographically. Among those, 48 patients showed no 
progression of structural damage defined by a change from baseline in the mTSS of 0.5 or less. At 
10 years, 79 of 207 patients originally treated with 40 mg Humira every other week were evaluated 
radiographically. Among those, 40 patients showed no progression of structural damage defined by a 
change from baseline in the mTSS of 0.5 or less. 



69 

 
Table 10 Radiographic Mean Changes Over 12 Months in RA Study III 

 
 Placebo/ 

MTXa 
Humira/MTX 
40 mg every 
other week 

Placebo/MTX-
Humira/MTX (95% 

Confidence 
Intervalb)

p-value 

Total Sharp Score 2.7 0.1 2.6 (1.4, 3.8) < 0.001c 

Erosion score 1.6 0.0 1.6 (0.9, 2.2) < 0.001 
JSNd score 1.0 0.1 0.9 (0.3, 1.4)   0.002 

amethotrexate 
b95% confidence intervals for the differences in change scores between methotrexate and Humira.  
cBased on rank analysis  
dJoint Space Narrowing 
 
In RA study V, structural joint damage was assessed radiographically and expressed as change in modified 
Total Sharp Score (see Table 11). 
 

Table 11 Radiographic Mean Changes at Week 52 in RA Study V 
 

 

MTX 
n=257 
(95% 

confidence 
interval) 

Humira 
n=274 
(95% 

confidence 
interval)

Humira/MTX 
n=268 
(95% 

confidence 
interval)

p-valuea p-valueb p-valuec 

Total Sharp 
Score 

5.7 (4.2-7.3) 3.0 (1.7-4.3) 1.3 (0.5-2.1) < 0.001 0.0020 < 0.001 

Erosion score 3.7 (2.7-4.7) 1.7 (1.0-2.4) 0.8 (0.4-1.2) < 0.001 0.0082 < 0.001
JSN score 2.0 (1.2-2.8) 1.3 (0.5-2.1) 0.5 (0-1.0) < 0.001 0.0037 0.151

a p-value is from the pairwise comparison of methotrexate monotherapy and Humira/methotrexate 
combination therapy using the Mann-Whitney U test. 

b p-value is from the pairwise comparison of Humira monotherapy and Humira/methotrexate 
combination therapy using the Mann-Whitney U test  

c p-value is from the pairwise comparison of Humira monotherapy and methotrexate monotherapy 
using the Mann-Whitney U test 

 
Following 52 weeks and 104 weeks of treatment, the percentage of patients without progression (change 
from baseline in modified Total Sharp Score  0.5) was significantly higher with Humira/methotrexate 
combination therapy (63.8% and 61.2% respectively) compared to methotrexate monotherapy (37.4% and 
33.5% respectively, p < 0.001) and Humira monotherapy (50.7%, p < 0.002 and 44.5%, p < 0.001 
respectively). 
 
In the open-label extension of RA study V, the mean change from baseline at Year 10 in the modified 
Total Sharp Score was 10.8, 9.2 and 3.9 in patients originally randomized to methotrexate monotherapy, 
Humira monotherapy and Humira/methotrexate combination therapy, respectively. The corresponding 
proportions of patients with no radiographic progression were 31.3%, 23.7% and 36.7% respectively. 
 
Quality of life and physical function 
 
Health-related quality of life and physical function were assessed using the disability index of the Health 
Assessment Questionnaire (HAQ) in the four original adequate and well-controlled trials, which was a 
pre-specified primary endpoint at Week 52 in RA study III. All doses/schedules of Humira in all four 
studies showed statistically significantly greater improvement in the disability index of the HAQ from 



70 

baseline to Month 6 compared to placebo and in RA study III the same was seen at Week 52. Results from 
the Short Form Health Survey (SF 36) for all doses/schedules of Humira in all four studies support these 
findings, with statistically significant physical component summary (PCS) scores, as well as statistically 
significant pain and vitality domain scores for the 40 mg every other week dose. A statistically significant 
decrease in fatigue as measured by functional assessment of chronic illness therapy (FACIT) scores was 
seen in all three studies in which it was assessed (RA studies I, III, IV). 
 
In RA study III, most subjects who achieved improvement in physical function and continued treatment 
maintained improvement through Week 520 (120 months) of open-label treatment. Improvement in 
quality of life was measured up to Week 156 (36 months) and improvement was maintained through that 
time. 
 
In RA study V, the improvement in the HAQ disability index and the physical component of the SF 36 
showed greater improvement (p < 0.001) for Humira/methotrexate combination therapy versus 
methotrexate monotherapy and Humira monotherapy at Week 52, which was maintained through 
Week 104. Among the 250 subjects who completed the open-label extension study, improvements in 
physical function were maintained through 10 years of treatment. 
 
Adult plaque psoriasis 
 
The safety and efficacy of Humira were studied in adult patients with chronic plaque psoriasis ( 10% 
BSA involvement and PASI  12 or  10) who were candidates for systemic therapy or phototherapy in 
randomised, double-blind studies. 73% of patients enrolled in Psoriasis Studies I and II had received prior 
systemic therapy or phototherapy. The safety and efficacy of Humira were also studied in adult patients 
with moderate to severe chronic plaque psoriasis with concomitant hand and/or foot psoriasis who were 
candidates for systemic therapy in a randomised double-blind study (Psoriasis Study III).   
 
Psoriasis Study I (REVEAL) evaluated 1,212 patients within three treatment periods. In period A, patients 
received placebo or Humira at an initial dose of 80 mg followed by 40 mg every other week starting one 
week after the initial dose. After 16weeks of therapy, patients who achieved at least a PASI 75 response 
(PASI score improvement of at least 75% relative to baseline), entered period B and received open-label 
40 mg Humira every other week. Patients who maintained PASI 75 response at Week 33 and were 
originally randomised to active therapy in Period A, were re-randomised in period C to receive 40 mg 
Humira every other week or placebo for an additional 19 weeks. Across all treatment groups, the mean 
baseline PASI score was 18.9 and the baseline PGA score ranged from “moderate” (53% of subjects 
included) to “severe” (41%) to “very severe” (6%). 
 
Psoriasis Study II (CHAMPION) compared the efficacy and safety of Humira versus methotrexate and 
placebo in 271 patients. Patients received placebo, an initial dose of MTX 7.5 mg and thereafter dose 
increases up to Week 12, with a maximum dose of 25 mg or an initial dose of 80 mg Humira followed by 
40 mg every other week (starting one week after the initial dose) for 16 weeks. There are no data available 
comparing Humira and MTX beyond 16 weeks of therapy. Patients receiving MTX who achieved a 
PASI 50 response at Week 8 and/or 12 did not receive further dose increases. Across all treatment 
groups, the mean baseline PASI score was 19.7 and the baseline PGA score ranged from “mild” (<1%) to 
“moderate” (48%) to “severe” (46%) to “very severe” (6%). 
 
Patients participating in all Phase 2 and Phase 3 psoriasis studies were eligible to enrol into an open-label 
extension trial, where Humira was given for at least an additional 108 weeks. 
 
In Psoriasis Studies I and II, a primary endpoint was the proportion of patients who achieved a PASI 75 
response from baseline at Week 16 (see Tables 12 and 13). 



71 

 
Table 12 

Ps Study I (REVEAL)  - Efficacy Results at 16 Weeks 

 
Placebo 
N=398 
n (%) 

Humira 40 mg eow 
N=814 
n (%) 

    PASI 75a 26 (6.5) 578 (70.9)b 
    PASI 100 3 (0.8) 163 (20.0)b 
    PGA: Clear/minimal 17 (4.3) 506 (62.2)b 
a Percent of patients achieving PASI75 response was calculated as centre-
adjusted rate 
b p<0.001, Humira vs. placebo

 

Table 13 
 Ps Study II (CHAMPION) Efficacy Results at 16 Weeks 

 Placebo 
N=53 
n (%)

MTX 
N=110 
n (%)

Humira 40 mg eow 
N=108 
n (%) 

    PASI 75 10 (18.9) 39 (35.5) 86 (79.6) a, b 
    PASI 100 1 (1.9) 8 (7.3) 18 (16.7) c, d 
    PGA: 
Clear/minimal 

6 (11.3) 33 (30.0) 79 (73.1) a, b 

a p<0.001 Humira vs. placebo 
b p<0.001 Humira vs. methotrexate 
c p<0.01 Humira vs. placebo 
d p<0.05 Humira vs. methotrexate

 
In Psoriasis Study I, 28% of patients who were PASI 75 responders and were re-randomised to placebo at 
Week 33 compared to 5% continuing on Humira, p<0.001, experienced “loss of adequate response” (PASI 
score after Week 33 and on or before Week 52 that resulted in a <PASI 50 response relative to baseline 
with a minimum of a 6-point increase in PASI score relative to Week 33). Of the patients who lost 
adequate response after re-randomisation to placebo who then enrolled into the open-label extension trial, 
38% (25/66) and 55% (36/66) regained PASI 75 response after 12 and 24 weeks of re-treatment, 
respectively. 
 
A total of 233 PASI 75 responders at Week 16 and Week 33 received continuous Humira therapy for 
52 weeks in Psoriasis Study I, and continued Humira in the open-label extension trial. PASI 75 and PGA 
of clear or minimal response rates in these patients were 74.7% and 59.0%, respectively, after an 
additional 108 weeks of open-label therapy (total of 160 weeks). In an analysis in which all patients who 
dropped out of the study for adverse events or lack of efficacy, or who dose-escalated, were considered 
non-responders, PASI 75 and PGA of clear or minimal response rates in these patients were 69.6% and 
55.7%, respectively, after an additional 108 weeks of open-label therapy (total of 160 weeks). 
 
A total of 347 stable responders participated in a withdrawal and retreatment evaluation in an open-label 
extension study. During the withdrawal period, symptoms of psoriasis returned over time with a median 
time to relapse (decline to PGA “moderate” or worse) of approximately 5 months. None of these patients 
experienced rebound during the withdrawal period. A total of 76.5% (218/285) of patients who entered the 
retreatment period had a response of PGA “clear” or “minimal” after 16 weeks of retreatment, irrespective 
of whether they relapsed during withdrawal (69.1%[123/178] and 88.8% [95/107] for patients who 
relapsed and who did not relapse during the withdrawal period, respectively). A similar safety profile was 
observed during retreatment as before withdrawal. 
 



72 

Significant improvements at Week 16 from baseline compared to placebo (Studies I and II) and MTX 
(Study II) were demonstrated in the DLQI (Dermatology Life Quality Index). In Study I, improvements in 
the physical and mental component summary scores of the SF-36 were also significant compared to 
placebo. 
 
In an open-label extension study, for patients who dose escalated from 40 mg every other week to 40 mg 
weekly due to a PASI response below 50%, 26.4% (92/349) and 37.8% (132/349) of patients achieved 
PASI 75 response at Week 12 and 24, respectively. 
 
Psoriasis Study III (REACH) compared the efficacy and safety of Humira versus placebo in 72 patients 
with moderate to severe chronic plaque psoriasis and hand and/or foot psoriasis. Patients received an 
initial dose of 80 mg Humira followed by 40 mg every other week (starting one week after the initial dose) 
or placebo for 16 weeks. At Week 16, a statistically significantly greater proportion of patients who 
received Humira achieved PGA of 'clear' or 'almost clear' for the hands and/or feet compared to patients 
who received placebo (30.6% versus 4.3%, respectively [P = 0.014]). 
 
Psoriasis Study IV compared efficacy and safety of Humira versus placebo in 217 adult patients with 
moderate to severe nail psoriasis. Patients received an initial dose of 80 mg Humira followed by 40 mg 
every other week (starting one week after the initial dose) or placebo for 26 weeks followed by open-label 
Humira treatment for an additional 26 weeks. Nail psoriasis assessments included the Modified Nail 
Psoriasis Severity Index (mNAPSI), the Physician’s Global Assessment of Fingernail Psoriasis (PGA-F) 
and the Nail Psoriasis Severity Index (NAPSI) (see Table 14). Humira demonstrated a treatment benefit in 
nail psoriasis patients with different extents of skin involvement (BSA≥10% (60% of patients) and 
BSA<10% and ≥5% (40% of patients)).     
 

Table 14 
Ps Study IV Efficacy Results at 16, 26 and 52 Weeks 

Endpoint Week 16 
Placebo-Controlled

Week 26 
Placebo-Controlled

Week 52 
Open-label

Placebo 
N=108 

Humira 
40 mg eow 

N=109

Placebo
N=108 

Humira 
40 mg eow 

N=109

Humira 
40 mg eow  

N=80 
≥ mNAPSI 75 (%) 2.9 26.0a 3.4 46.6a 65.0 
PGA-F clear/minimal and 
≥2-grade improvement (%) 

2.9 29.7a 6.9 48.9a 61.3 

Percent Change in Total 
Fingernail NAPSI (%) 

-7.8 -44.2 a -11.5 -56.2a -72.2 

a p<0.001, Humira vs. placebo  
 
Humira treated patients showed statistically significant improvements at Week 26 compared with placebo 
in the DLQI.  
 
Adult hidradenitis suppurativa 
 
The safety and efficacy of Humira were assessed in randomised, double-blind, placebo-controlled studies 
and an open-label extension study in adult patients with moderate to severe hidradenitis suppurativa (HS) 
who were intolerant, had a contraindication or an inadequate response to at least a 3-month trial of 
systemic antibiotic therapy. The patients in HS-I and HS-II had Hurley Stage II or III disease with at least 
3 abscesses or inflammatory nodules. 
 
Study HS-I (PIONEER I) evaluated 307 patients with 2 treatment periods. In Period A, patients received 
placebo or Humira at an initial dose of 160 mg at Week 0, 80 mg at Week 2, and 40 mg every week 
starting at Week 4 to Week 11. Concomitant antibiotic use was not allowed during the study. After 



73 

12 weeks of therapy, patients who had received Humira in Period A were re-randomised in Period B to 1 
of 3 treatment groups (Humira 40 mg every week, Humira 40 mg every other week, or placebo from Week 
12 to Week 35). Patients who had been randomised to placebo in Period A were assigned to receive 
Humira 40 mg every week in Period B. 
 
Study HS-II (PIONEER II) evaluated 326 patients with 2 treatment periods. In Period A, patients received 
placebo or Humira at an initial dose of 160 mg at Week 0 and 80 mg at Week 2 and 40 mg every week 
starting at Week 4 to Week 11. 19.3% of patients had continued baseline oral antibiotic therapy during the 
study.  After 12 weeks of therapy, patients who had received Humira in Period A were re-randomised in 
Period B to 1 of 3 treatment groups (Humira 40 mg every week, Humira 40 mg every other week, or 
placebo from Week 12 to Week 35). Patients who had been randomised to placebo in Period A were 
assigned to receive placebo in Period B. 
 
Patients participating in Studies HS-I and HS-II were eligible to enrol into an open-label extension study 
in which Humira 40mg was administered every week. Mean exposure in all adalimumab population was 
762 days. Throughout all 3 studies patients used topical antiseptic wash daily. 
 
Clinical Response 
 
Reduction of inflammatory lesions and prevention of worsening of abscesses and draining fistulas was 
assessed using Hidradenitis Suppurativa Clinical Response (HiSCR; at least a 50% reduction in total 
abscess and inflammatory nodule count with no increase in abscess count and no increase in draining 
fistula count relative to Baseline). Reduction in HS-related skin pain was assessed using a Numeric Rating 
Scale in patients who entered the study with an initial baseline score of 3 or greater on a 11 point scale.  
 
At Week 12, a significantly higher proportion of patients treated with Humira versus placebo achieved 
HiSCR.   At Week 12, a significantly higher proportion of patients in Study HS-II experienced a clinically 
relevant decrease in HS-related skin pain (see Table 15). Patients treated with Humira had significantly 
reduced risk of disease flare during the initial 12 weeks of treatment. 
 

Table 15:  Efficacy Results at 12 Weeks, HS Studies I and II 
 

 

HS Study I HS Study II 

Placebo
Humira 40 mg 

Weekly Placebo  
Humira 40 mg 

Weekly 

Hidradenitis Suppurativa 
Clinical Response (HiSCR)a   

N = 154 
40 (26.0%) 

N = 153 
64 (41.8%) * 

N=163 
45 (27.6%) 

N=163 
96 (58.9%) *** 

≥30% Reduction in Skin 
Painb 

N = 109 
27 (24.8%)

N = 122 
34 (27.9%)

N=111 
23 (20.7%) 

N=105 
48 (45.7%) ***

* P < 0.05, ***P < 0.001, Humira versus placebo  
a Among all randomised patients. 
b Among patients with baseline HS-related skin pain assessment ≥ 3, based on Numeric Rating 

Scale 0 – 10; 0 = no skin pain, 10 = skin pain as bad as you can imagine.
 
Treatment with Humira 40 mg every week significantly reduced the risk of worsening of abscesses and 
draining fistulas. Approximately twice the proportion of patients in the placebo group in the first 12 weeks 
of Studies HS-I and HS-II, compared with those in the Humira group experienced worsening of abscesses 
(23.0% vs 11.4%, respectively) and draining fistulas (30.0% vs 13.9%, respectively). 
 
Greater improvements at Week 12 from baseline compared to placebo were demonstrated in skin-specific 
health-related quality of life, as measured by the Dermatology Life Quality Index (DLQI; Studies HS-I 
and HS-II), patient global satisfaction with medication treatment as measured by the Treatment 



74 

Satisfaction Questionnaire - medication (TSQM; Studies HS-I and HS-II), and physical health as 
measured by the physical component summary score of the SF-36 (Study HS-I). 
 
In patients with at least a partial response to Humira 40 mg weekly at Week 12, the HiSCR rate at Week 
36 was higher in patients who continued weekly Humira than in patients in whom dosing frequency was 
reduced to every other week, or in whom treatment was withdrawn (see Table 16).   
 

Table 16:  Proportion of Patientsa Achieving HiSCRb at Weeks 24 and 36 After  
Treatment Reassignment from Weekly Humira at Week 12 

 

 

Placebo
(treatment 

withdrawal) 
N = 73 

Humira 40 mg 
every other week 

N = 70 

Humira 40 mg 
weekly 
N = 70 

Week 24 24 (32.9%) 36 (51.4%) 40 (57.1%) 
Week 36 22 (30.1%) 28 (40.0%) 39 (55.7%) 

a Patients with at least a partial response to Humira 40 mg weekly after 12 
weeks of treatment. 

b Patients meeting protocol-specified criteria for loss of response or no 
improvement were required to discontinue from the studies and were 
counted as nonresponders.

   
Among patients who were at least partial responders at Week 12, and who received continuous weekly 
Humira therapy, the HiSCR rate at Week 48 was 68.3% and at Week 96 was 65.1%. Longer term 
treatment with Humira 40 mg weekly for 96 weeks identified no new safety findings. 
 
Among patients whose Humira treatment was withdrawn at Week 12 in Studies HS-I and HS-II, the 
HiSCR rate 12 weeks after re-introduction of Humira 40 mg weekly returned to levels similar to that 
observed before withdrawal (56.0 %). 
 
Adult Crohn’s disease 
 
The safety and efficacy of Humira were assessed in over 1500 patients with moderately to severely active 
Crohn’s disease (Crohn’s Disease Activity Index (CDAI)  220 and  450) in randomised, double-blind, 
placebo-controlled studies. Concomitant stable doses of aminosalicylates, corticosteroids, and/or 
immunomodulatory agents were permitted and 80% of patients continued to receive at least one of these 
medications.  
 
Induction of clinical remission (defined as CDAI < 150) was evaluated in two studies, CD Study I 
(CLASSIC I) and CD Study II (GAIN). In CD Study I, 299 TNF-antagonist naive patients were 
randomised to one of four treatment groups; placebo at Weeks 0 and 2, 160 mg Humira at Week 0 and 
80 mg at Week 2, 80 mg at Week 0 and 40 mg at Week 2, and 40 mg at Week 0 and 20 mg at Week 2. In 
CD Study II, 325 patients who had lost response or were intolerant to infliximab were randomised to 
receive either 160 mg Humira at Week 0 and 80 mg at Week 2 or placebo at Weeks 0 and 2. The primary 
non-responders were excluded from the studies and therefore these patients were not further evaluated. 
 
Maintenance of clinical remission was evaluated in CD study III (CHARM). In CD Study III, 854 patients 
received open-label 80 mg at Week 0 and 40 mg at Week 2. At Week 4 patients were randomised to 
40 mg every other week, 40 mg every week, or placebo with a total study duration of 56 weeks. Patients in 
clinical response (decrease in CDAI ≥ 70) at Week 4 were stratified and analysed separately from those 
not in clinical response at Week 4. Corticosteroid taper was permitted after Week 8.  
 
CD study I and CD study II induction of remission and response rates are presented in Table 17. 



75 

 
Table 17 

Induction of Clinical Remission and Response 
(Percent of Patients) 

 CD Study I: Infliximab Naive 
Patients 

CD Study II: Infliximab 
Experienced Patients 

 Placebo 
N=74 

Humira 
80/40 mg 

N = 75 

Humira  
160/80 mg 

N=76 

Placebo 
N=166 

Humira  
160/80 mg 

N=159 

Week 4      

Clinical remission 12% 24% 36%* 7% 21%* 

Clinical response (CR-
100) 

24% 37% 49%** 25% 38%** 

All p-values are pairwise comparisons of proportions for Humira versus placebo 
* p < 0.001 
** p < 0.01 

 
Similar remission rates were observed for the 160/80 mg and 80/40 mg induction regimens by Week 8 and 
adverse events were more frequently noted in the 160/80 mg group. 
 
In CD Study III, at Week 4, 58% (499/854) of patients were in clinical response and were assessed in the 
primary analysis. Of those in clinical response at Week 4, 48% had been previously exposed to other TNF-
antagonists. Maintenance of remission and response rates are presented in Table 18. Clinical remission 
results remained relatively constant irrespective of previous TNF-antagonist exposure. 
 
Disease-related hospitalisations and surgeries were statistically significantly reduced with adalimumab 
compared with placebo at Week 56. 
 

Table 18 
Maintenance of Clinical Remission and Response 

(Percent of Patients) 

 Placebo 40 mg Humira 
every other week 

40 mg Humira
every week 

Week 26 N=170 N=172 N=157 

Clinical remission 17% 40%* 47%* 

Clinical response (CR-100) 27% 52%* 52%* 

Patients in steroid-free remission  
for >=90 daysa 

3% (2/66) 19% (11/58)** 15% (11/74)** 

Week 56 N=170 N=172 N=157 

Clinical remission 12% 36%* 41%* 

Clinical response (CR-100) 17% 41%* 48%* 

Patients in steroid-free remission  
for >=90 daysa 

5% (3/66) 29% (17/58)* 20% (15/74)** 

* p < 0.001 for Humira versus placebo pairwise comparisons of proportions 
** p < 0.02 for Humira versus placebo pairwise comparisons of proportions 
a Of those receiving corticosteroids at baseline 

 



76 

Among patients who were not in response at Week 4, 43% of Humira maintenance patients responded by 
Week 12 compared to 30% of placebo maintenance patients. These results suggest that some patients who 
have not responded by Week 4 benefit from continued maintenance therapy through Week 12. Therapy 
continued beyond 12 weeks did not result in significantly more responses (see section 4.2).   
 
117/276 patients from CD study I and 272/777 patients from CD studies II and III were followed through 
at least 3 years of open-label adalimumab therapy. 88 and 189 patients, respectively, continued to be in 
clinical remission. Clinical response (CR-100) was maintained in 102 and 233 patients, respectively. 
 
Quality of life 
 
In CD Study I and CD Study II, statistically significant improvement in the disease-specific inflammatory 
bowel disease questionnaire (IBDQ) total score was achieved at Week 4 in patients randomised to Humira 
80/40 mg and 160/80 mg compared to placebo and was seen at Weeks 26 and 56 in CD Study III as well 
among the adalimumab treatment groups compared to the placebo group. 
 
Adult Uveitis 
 
The safety and efficacy of Humira were assessed in adult patients with non-infectious intermediate, 
posterior, and panuveitis, excluding patients with isolated anterior uveitis, in two randomised, double-
masked, placebo-controlled studies (UV I and II). Patients received placebo or Humira at an initial dose of 
80 mg followed by 40 mg every other week starting one week after the initial dose. Concomitant stable 
doses of one non-biologic immunosuppressant were permitted.  
 
Study UV I evaluated 217 patients with active uveitis despite treatment with corticosteroids (oral 
prednisone at a dose of 10 to 60 mg/day). All patients received a 2-week standardised dose of prednisone 
60 mg/day at study entry followed by a mandatory taper schedule, with complete corticosteroid 
discontinuation by Week 15.  
 
Study UV II evaluated 226 patients with inactive uveitis requiring chronic corticosteroid treatment (oral 
prednisone 10 to 35 mg/day) at baseline to control their disease. Patients subsequently underwent a 
mandatory taper schedule, with complete corticosteroid discontinuation by Week 19.  
 
The primary efficacy endpoint in both studies was ´time to treatment failure´. Treatment failure was 
defined by a multi-component outcome based on inflammatory chorioretinal and/or inflammatory retinal 
vascular lesions, anterior chamber (AC) cell grade, vitreous haze (VH) grade and best corrected visual 
acuity (BCVA).  
 
Patients who completed Studies UV I and UV II were eligible to enroll in an uncontrolled long-term 
extension study with an originally planned duration of 78 weeks. Patients were allowed to continue on 
study medication beyond Week 78 until they had access to Humira. 
 
Clinical Response 
 
Results from both studies demonstrated statistically significant reduction of the risk of treatment failure in 
patients treated with Humira versus patients receiving placebo (See Table 19). Both studies demonstrated 
an early and sustained effect of Humira on the treatment failure rate versus placebo (see Figure 1).  
 



77 

Table 19 
Time to Treatment Failure in Studies UV I and UV II 

 
Analysis 
 Treatment 

N Failure 
N (%) 

Median Time to 
Failure (months) 

HRa CI 95% 
for HRa 

P Value b 

Time to Treatment Failure At or After Week 6 in Study UV I   
Primary analysis (ITT)   
 Placebo 107 84 (78.5) 3.0 -- -- -- 
 Adalimumab 110 60 (54.5) 5.6 0.50 0.36, 0.70  < 0.001
Time to Treatment Failure At or After Week 2 in Study UV II 
Primary analysis (ITT)   
 Placebo 111 61 (55.0) 8.3 -- -- -- 
 Adalimumab 115 45 (39.1) NEc 0.57 0.39, 0.84 0.004 

Note: Treatment failure at or after Week 6 (Study UV I), or at or after Week 2 (Study UV II), was counted 
as event. Drop outs due to reasons other than treatment failure were censored at the time of dropping out. 
a HR of adalimumab vs placebo from proportional hazards regression with treatment as factor. 
b 2-sided P value from log rank test. 
c NE = not estimable. Fewer than half of at-risk subjects had an event.  
 
Figure 1: Kaplan-Meier Curves Summarizing Time to Treatment Failure on or after Week 6 (Study 

UV I) or Week 2 (Study UV II) 
 

T
R

E
A

T
M

E
N

T
 F

A
IL

U
R

E
 R

A
T

E
 (

%
) 

 TIME (MONTHS)
 Study UV I                        Treatment Placebo Adalimumab 



78 

T
R

E
A

T
M

E
N

T
 F

A
IL

U
R

E
 R

A
T

E
 (

%
) 

 TIME (MONTHS)
 Study UV II                       Treatment Placebo Adalimumab 

Note: P# = Placebo (Number of Events/Number at Risk); A# = HUMIRA (Number of 
Events/Number at Risk). 

 
In Study UV I statistically significant differences in favour of adalimumab versus placebo were observed 
for each component of treatment failure. In Study UV II, statistically significant differences were observed 
for visual acuity only, but the other components were numerically in favour of adalimumab. 
 
Of the 424 subjects included in the uncontrolled long-term extension of Studies UV I and UV II, 60 
subjects were regarded ineligible (e.g. due to deviations or due to complications secondary to diabetic 
retinopathy, due to cataract surgery or vitrectomy) and were excluded from the primary analysis of 
efficacy. Of the 364 remaining patients, 269 evaluable patients (74%) reached 78 weeks of open-label 
adalimumab treatment. Based on the observed data approach, 216 (80.3%) were in quiescence (no active 
inflammatory lesions, AC cell grade  ≤ 0.5+, VH grade ≤ 0.5+) with a concomitant steroid dose ≤ 7.5 mg 
per day, and 178 (66.2%) were in steroid-free quiescence. BCVA was either improved or maintained (< 5 
letters deterioration) in 88.6% of the eyes at week 78. Data beyond Week 78 were generally consistent 
with these results but the number of enrolled subjects declined after this time. Overall, among the patients 
who discontinued the study, 18% discontinued due to adverse events, and 8% due to insufficient response 
to adalimumab treatment. 
 
Quality of Life 
 
Patient reported outcomes regarding vision-related functioning were measured in both clinical studies, 
using the NEI VFQ-25. Humira was numerically favoured for the majority of subscores with statistically 
significant mean differences for general vision, ocular pain, near vision, mental health, and total score in 
Study UV I, and for general vision and mental health in Study UV II. Vision related effects were not 
numerically in favour of Humira for colour vision in Study UVI and for colour vision, peripheral vision 
and near vision in Study UV II. 
 
Immunogenicity 
 
Formation of anti-adalimumab antibodies is associated with increased clearance and reduced efficacy of 
adalimumab. There is no apparent correlation between the presence of anti-adalimumab antibodies and the 
occurrence of adverse events. 
 



79 

In patients with polyarticular juvenile idiopathic arthritis who were 4 to 17 years, anti- adalimumab 
antibodies were identified in 15.8% (27/171) of patients treated with adalimumab. In patients not given 
concomitant methotrexate, the incidence was 25.6% (22/86) compared to 5.9% (5/85) when adalimumab 
was used as add-on to methotrexate. In patients with polyarticular juvenile idiopathic arthritis who were 
2 to < 4 years old or aged 4 and above weighing <15 kg, anti-adalimumab antibodies were identified in 
7% (1/15) of patients, and the one patient was receiving concomitant methotrexate. 
 
In patients with enthesitis-related arthritis, anti-adalimumab antibodies were identified in 10.9% (5/46) of 
patients treated with adalimumab. In patients not given concomitant methotrexate, the incidence was 
13.6% (3/22), compared to 8.3% (2/24) when adalimumab was used as add-on to methotrexate. 
 
Patients in rheumatoid arthritis studies I, II and III were tested at multiple time points for anti-adalimumab 
antibodies during the 6 to 12 month period. In the pivotal trials, anti-adalimumab antibodies were 
identified in 5.5% (58/1053) of patients treated with adalimumab, compared to 0.5% (2/370) on placebo. 
In patients not given concomitant methotrexate, the incidence was 12.4%, compared to 0.6% when 
adalimumab was used as add-on to methotrexate.   
 
In patients with paediatric psoriasis, anti-adalimumab antibodies were identified in 5/38 subjects (13%) 
treated with 0.8 mg/kg adalimumab monotherapy. 
 
In adult patients with psoriasis, anti-adalimumab antibodies were identified in 77/920 subjects (8.4%) 
treated with adalimumab monotherapy. 
 
In adult plaque psoriasis patients on long term adalimumab monotherapy who participated in a withdrawal 
and retreatment study, the rate of antibodies to adalimumab after retreatment (11 of 482 subjects, 2.3%) 
was similar to the rate observed prior to withdrawal (11 of 590 subjects, 1.9%). 
 
In patients with moderately to severely active paediatric Crohn’s disease, the rate of anti-adalimumab 
antibody development in patients receiving adalimumab was 3.3%.  
 
In adult patients with Crohn’s disease, anti-adalimumab antibodies were identified in 7/269 subjects 
(2.6%). 
 
In adult patients with non-infectious uveitis, anti-adalimumab antibodies were identified in 4.8% (12/249) 
of patients treated with adalimumab. 
 
In patients with moderately to severely active paediatric ulcerative colitis, the rate of anti-adalimumab 
antibody development in patients receiving adalimumab was 3%. 
 
Because immunogenicity analyses are product-specific, comparison of antibody rates with those from 
other products is not appropriate. 
 
Paediatric population 
 
Juvenile idiopathic arthritis (JIA) 
 
Polyarticular juvenile idiopathic arthritis (pJIA) 
 
The safety and efficacy of Humira was assessed in two studies (pJIA I and II) in children with active 
polyarticular or polyarticular course juvenile idiopathic arthritis, who had a variety of JIA onset types 
(most frequently rheumatoid-factor negative or positive polyarthritis and extended oligoarthritis). 
 
pJIA I 



80 

 

The safety and efficacy of Humira were assessed in a multicentre, randomised, double-blind, 
parallel − group study in 171 children (4-17 years old) with polyarticular JIA. In the open-label lead in 
phase (OL LI) patients were stratified into two groups, MTX (methotrexate)-treated or non- MTX-treated. 
Patients who were in the non-MTX stratum were either naïve to or had been withdrawn from MTX at 
least two weeks prior to study drug administration. Patients remained on stable doses of non-steroidal 
anti-inflammatory drugs (NSAIDs) and or prednisone ( 0.2 mg /kg/day or 10 mg/day maximum). In the 
OL LI phase all patients received 24 mg/m2 up to a maximum of 40 mg Humira every other week for 
16 weeks. The distribution of patients by age and minimum, median and maximum dose received during 
the OL LI phase is presented in Table 20. 
 

Table 20 
Distribution of patients by age and adalimumab dose received during the OL LI phase 

 
Age Group Number of patients at Baseline 

n (%) 
Minimum, median and 
maximum dose 

4 to 7 years 31 (18.1) 10, 20 and 25 mg 
8 to 12 years 71 (41.5) 20, 25 and 40 mg 
13 to 17 years 69 (40.4) 25, 40 and 40 mg 

 
Patients demonstrating a Paediatric ACR 30 response at Week 16 were eligible to be randomised into the 
double blind (DB) phase and received either Humira 24 mg/m2 up to a maximum of 40 mg, or placebo 
every other week for an additional 32 weeks or until disease flare. Disease flare criteria were defined as a 
worsening of  30% from baseline in  3 of 6 Paediatric ACR core criteria,  2 active joints, and 
improvement of  30% in no more than 1 of the 6 criteria. After 32 weeks or at disease flare, patients 
were eligible to enrol into the open label extension phase.  
 

Table 21 
Ped ACR 30 Responses in the JIA study 

 
Stratum MTX Without MTX 
Phase  
OL-LI 16 weeks  

Ped ACR 30 
response (n/N) 

94.1% (80/85) 74.4% (64/86) 

                                                          Efficacy Outcomes
Double Blind 32 weeks Humira / MTX 

(N = 38) 
 

Placebo / MTX 
(N = 37) 

Humira  
(N = 30) 

Placebo 
(N = 28) 

Disease flares at 
the end of 
32weeksa (n/N) 

36.8% (14/38) 64.9% (24/37)b 43.3% (13/30) 71.4% 
(20/28)c 

Median time to 
disease flare 

>32 weeks 20 weeks >32 weeks 14 weeks 

 

a Ped ACR 30/50/70 responses Week 48 significantly greater than those of placebo treated patients  
b p = 0.015 
c p = 0.031 
 

Amongst those who responded at Week 16 (n=144), the Paediatric ACR 30/50/70/90 responses were 
maintained for up to six years in the OLE phase in patients who received Humira throughout the study. 



81 

Over all 19 subjects, of which 11 of the baseline age group 4 to 12 and 8 of the baseline age group 13 to 
17 years were treated 6 years or longer. 
 
Overall responses were generally better and, fewer patients developed antibodies when treated with the 
combination of Humira and MTX compared to Humira alone. Taking these results into consideration, 
Humira is recommended for use in combination with MTX and for use as monotherapy in patients for 
whom MTX use is not appropriate (see section 4.2).  
 
pJIA II 
 
The safety and efficacy of Humira was assessed in an open-label, multicentre study in 32 children (2 - 
<4 years old or aged 4 and above weighing < 15 kg) with moderately to severely active polyarticular JIA. 
The patients received 24 mg/m2 body surface area (BSA) of Humira up to a maximum of 20 mg every 
other week as a single dose via SC injection for at least 24 weeks. During the study, most subjects used 
concomitant MTX, with fewer reporting use of corticosteroids or NSAIDs. 
 
At Week 12 and Week 24, PedACR30 response was 93.5% and 90.0%, respectively, using the observed 
data approach. The proportions of subjects with PedACR50/70/90 at Week 12 and Week 24 were 
90.3%/61.3%/38.7% and 83.3%/73.3%/36.7%, respectively. Amongst those who responded (Paediatric 
ACR 30) at Week 24 (n=27 out of 30 patients), the Paediatric ACR 30 responses were maintained for up 
to 60 weeks in the OLE phase in patients who received Humira throughout this time period. Overall, 20 
subjects were treated for 60 weeks or longer. 
 
Enthesitis-related arthritis 
 
The safety and efficacy of Humira were assessed in a multicentre, randomised, double-blind study in 46 
paediatric patients (6 to 17 years old) with moderate enthesitis-related arthritis. Patients were randomised 
to receive either 24 mg/m2 body surface area (BSA) of Humira up to a maximum of 40 mg, or placebo 
every other week for 12 weeks. The double-blind period is followed by an open-label (OL) period during 
which patients received 24 mg/m2 BSA of Humira up to a maximum of 40 mg every other week 
subcutaneously for up to an additional 192 weeks. The primary endpoint was the percent change from 
Baseline to Week 12 in the number of active joints with arthritis (swelling not due to deformity or joints 
with loss of motion plus pain and/or tenderness), which was achieved with mean percent decrease of -
62.6% (median percent change -88.9%) in patients in the Humira group compared to -11.6% (median 
percent change -50.0%) in patients in the placebo group. Improvement in number of active joints with 
arthritis was maintained during the OL period through Week 156 for the 26 of 31 (84%) patients in the 
Humira group who remained in the study. Although not statistically significant, the majority of patients 
demonstrated clinical improvement in secondary endpoints such as number of sites of enthesitis, tender 
joint count (TJC), swollen joint count (SJC), Paediatric ACR 50 response, and Paediatric ACR 70 
response. 
 
Paediatric plaque psoriasis 

 

The efficacy of Humira was assessed in a randomised, double-blind, controlled study of 114 paediatric 
patients from 4 years of age with severe chronic plaque psoriasis (as defined by a Physician’s Global 
Assessment (PGA) ≥ 4 or > 20% BSA involvement or > 10% BSA involvement with very thick lesions or 
Psoriasis Area and Severity Index (PASI) ≥ 20 or ≥ 10 with clinically relevant facial, genital, or hand/ foot 
involvement) who were inadequately controlled with topical therapy and heliotherapy or phototherapy.  
 
Patients received Humira 0.8 mg/kg eow (up to 40 mg), 0.4 mg/kg eow (up to 20 mg), or methotrexate 0.1 
– 0.4 mg/kg weekly (up to 25 mg). At week 16, more patients randomised to Humira 0.8 mg/kg had 
positive efficacy responses (e.g., PASI 75) than those randomised to 0.4 mg/kg eow or MTX.   



82 

 
Table 22: Paediatric Plaque Psoriasis Efficacy Results at 16 Weeks 

 

 
MTXa 
N=37 

Humira 0.8 mg/kg eow 
N=38  

 PASI 75b 12 (32.4%) 22 (57.9%) 
 PGA: Clear/minimalc 15 (40.5%) 23 (60.5%) 
a MTX = methotrexate 
b P=0.027, Humira 0.8 mg/kg versus MTX 
c P=0.083, Humira 0.8 mg/kg versus MTX

 
Patients who achieved PASI 75 and PGA clear or minimal were withdrawn from treatment for up to 
36 weeks and monitored for loss of disease control (i.e. a worsening of PGA by at least 2 grades). Patients 
were then re-treated with adalimumab 0.8 mg/kg eow for an additional 16 weeks and response rates 
observed during retreatment were similar to the previous double-blind period:  PASI 75 response of 78.9% 
(15 of 19 subjects) and PGA clear or minimal of 52.6% (10 of 19 subjects). 
 
In the open label period of the study, PASI 75 and PGA clear or minimal responses were maintained for 
up to an additional 52 weeks with no new safety findings. 
 
Adolescent hidradenitis suppurativa 
 
There are no clinical trials with Humira in adolescent patients with HS. Efficacy of adalimumab for the 
treatment of adolescent patients with HS is predicted based on the demonstrated efficacy and exposure-
response relationship in adult HS patients and the likelihood that the disease course, pathophysiology, and 
drug effects are substantially similar to that of adults at the same exposure levels. Safety of the 
recommended adalimumab dose in the adolescent HS population is based on cross-indication safety 
profile of adalimumab in both adults and paediatric patients at similar or more frequent doses (see section 
5.2). 
 
Paediatric Crohn’s disease 
 
Humira was assessed in a multicentre, randomised, double-blind clinical trial designed to evaluate the 
efficacy and safety of induction and maintenance treatment with doses dependent on body weight 
(< 40 kg or ≥ 40 kg) in 192 paediatric subjects between the ages of 6 and 17 (inclusive) years, with 
moderate to severe Crohn´s disease (CD) defined as Paediatric Crohn's Disease Activity Index (PCDAI) 
score > 30. Subjects had to have failed conventional therapy (including a corticosteroid and/or an 
immunomodulator) for CD. Subjects may also have previously lost response or been intolerant to 
infliximab.  
 
All subjects received open-label induction therapy at a dose based on their Baseline body weight: 160 mg 
at Week 0 and 80 mg at Week 2 for subjects ≥ 40 kg, and 80 mg and 40 mg, respectively, for subjects 
< 40 kg. 
 
At Week 4, subjects were randomised 1:1 based on their body weight at the time to either the Low Dose or 
Standard Dose maintenance regimens as shown in Table 23. 



83 

 
Table 23 

Maintenance regimen
Patient 
Weight 

Low dose Standard 
dose 

< 40 kg 10 mg eow 20 mg eow
≥ 40 kg 20 mg eow 40 mg eow

 
Efficacy results 
 
The primary endpoint of the study was clinical remission at Week 26, defined as PCDAI score  10. 
 
Clinical remission and clinical response (defined as reduction in PCDAI score of at least 15 points from 
Baseline) rates are presented in Table 24. Rates of discontinuation of corticosteroids or 
immunomodulators are presented in Table 25. 
 

Table 24 
Paediatric CD Study 

PCDAI Clinical Remission and Response 
 Standard Dose

40/20 mg eow 
N = 93 

Low Dose 
20/10 mg eow 

N = 95 

P value* 

Week 26    
   Clinical remission 38.7% 28.4% 0.075 
   Clinical response  59.1% 48.4% 0.073 
Week 52    
   Clinical remission 33.3% 23.2% 0.100 
   Clinical response 41.9% 28.4% 0.038 
* p value for Standard Dose versus Low Dose comparison.

 
Table 25 

Paediatric CD Study 
Discontinuation of Corticosteroids or Immunomodulators and Fistula Remission 

 Standard Dose
40/20 mg eow  

Low Dose 
20/10 mg eow  

P value1 

Discontinued corticosteroids N= 33 N=38  
Week 26 84.8% 65.8% 0.066 
Week 52 69.7% 60.5% 0.420 
Discontinuation of Immunomodulators2 N=60 N=57  
Week 52 30.0% 29.8% 0.983 
Fistula remission3 N=15 N=21  
Week 26 46.7% 38.1% 0.608 
Week 52, 40.0% 23.8% 0.303 
1  p value for Standard Dose versus Low Dose comparison. 
 2  Immunosuppressant therapy could only be discontinued at or after Week 26 at the 
investigator's discretion if the subject met the clinical response criterion  
3  defined as a closure of all fistulas that were draining at Baseline for at least 2 consecutive 
post-Baseline visits

 
Statistically significant increases (improvement) from Baseline to Week 26 and 52 in Body Mass Index 
and height velocity were observed for both treatment groups. 
 



84 

Statistically and clinically significant improvements from Baseline were also observed in both treatment 
groups for quality of life parameters (including IMPACT III). 
 
One hundred patients (n=100) from the Paediatric CD Study continued in an open-label long-term 
extension study. After 5 years of adalimumab therapy, 74.0% (37/50) of the 50 patients remaining in the 
study continued to be in clinical remission, and 92.0% (46/50) of patients continued to be in clinical 
response per PCDAI. 
 
Paediatric ulcerative colitis 
 
The safety and efficacy of Humira was assessed in a multicenter, randomized, double-blind, trial in 93 
paediatric patients from 5 to 17 years of age with moderate to severe ulcerative colitis (Mayo score 6 to 12 
with endoscopy subscore of 2 to 3 points, confirmed by centrally read endoscopy) who had an inadequate 
response or intolerance to conventional therapy. Approximately 16% of patients in the study had failed 
prior anti-TNF treatment. Patients who received corticosteroids at enrollment were allowed to taper their 
corticosteroid therapy after Week 4. 
 
In the induction period of the study, 77 patients were randomized 3:2 to receive double-blind treatment 
with Humira at an induction dose of 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2; or an induction dose of 2.4 mg/kg (maximum of 160 mg) at Week 
0, placebo at Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2. Both groups received 0.6 mg/kg 
(maximum of 40 mg) at Week 4 and Week 6. Following an amendment to the study design, the remaining 
16 patients who enrolled in the induction period received open-label treatment with Humira at the 
induction dose of 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 mg/kg (maximum of 
80 mg) at Week 2.  
 
At Week 8, 62 patients who demonstrated clinical response per Partial Mayo Score (PMS; defined as a 
decrease in PMS ≥ 2 points and ≥ 30% from Baseline) were randomized equally to receive double-blind 
maintenance treatment with Humira at a dose of 0.6 mg/kg (maximum of 40 mg) every week (ew), or a 
maintenance dose of 0.6 mg/kg (maximum of 40 mg) every other week (eow). Prior to an amendment to 
the study design, 12 additional patients who demonstrated clinical response per PMS were randomized to 
receive placebo but were not included in the confirmatory analysis of efficacy. 
 
Disease flare was defined as an increase in PMS of at least 3 points (for patients with PMS of 0 to 2 at 
Week 8), at least 2 points (for patients with PMS of 3 to 4 at Week 8), or at least 1 point (for patients with 
PMS of 5 to 6 at Week 8).  
 
Patients who met criteria for disease flare at or after Week 12 were randomized to receive a re-induction 
dose of 2.4 mg/kg (maximum of 160 mg) or a dose of 0.6 mg/kg (maximum of 40 mg) and continued to 
receive their respective maintenance dose regimen afterwards.  
 

Efficacy Results 

 

The co-primary endpoints of the study were clinical remission per PMS (defined as PMS ≤ 2 and no 
individual subscore > 1) at Week 8, and clinical remission per FMS (Full Mayo Score) (defined as a Mayo 
Score ≤ 2 and no individual subscore > 1) at Week 52 in patients who achieved clinical response per PMS 
at Week 8. 
 
Clinical remission rates per PMS at Week 8 for patients in each of the Humira double-
blind induction groups are presented in Table 26.  



85 

Table 26: Clinical Remission per PMS at 8 Weeks  

 

Humiraa 
Maximum of 160 mg at Week 

0 / Placebo at Week 1  
N=30 

Humirab, c  
Maximum of 160 mg at Week 

0 and Week 1  
N=47 

Clinical remission 13/30 (43.3%) 28/47 (59.6%) 

a Humira 2.4 mg/kg (maximum of 160 mg) at Week 0, placebo at Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2  
b Humira 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2  
c Not including open-label Induction dose of Humira 2.4 mg/kg (maximum of 160 mg) at 
Week 0 and Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2 
Note 1: Both induction groups received 0.6 mg/kg (maximum of 40 mg) at Week 4 and 
Week 6  
Note 2: Patients with missing values at Week 8 were considered as not having met the 
endpoint  

 
At Week 52, clinical remission per FMS in Week 8 responders, clinical response per FMS (defined as a 
decrease in Mayo Score ≥ 3 points and ≥ 30% from Baseline) in Week 8 responders, mucosal healing per 
FMS (defined as an Mayo endoscopy score ≤ 1) in Week 8 responders, clinical remission per FMS in 
Week 8 remitters, and the proportion of subjects in corticosteroid-free remission per FMS in Week 8 
responders were assessed in patients who received Humira at the double-blind maximum 40 mg eow (0.6 
mg/kg) and maximum 40 mg ew (0.6 mg/kg) maintenance doses (Table 27).  
 

Table 27: Efficacy Results at 52 Weeks  
 

Humiraa   
Maximum of 40 mg eow 

N=31 

Humirab   
Maximum of 40 mg ew  

N=31 

Clinical remission in Week 
8 PMS responders  

9/31 (29.0%)  14/31 (45.2%) 

Clinical response in Week 8 
PMS responders  

19/31 (61.3%)  21/31 (67.7%)  

Mucosal healing in 
Week 8 PMS responders  

12/31 (38.7%)  16/31 (51.6%)  

Clinical remission in Week 
8 PMS remitters  

9/21 (42.9%)  10/22 (45.5%)  

Corticosteroid-free 
remission in Week 8 
PMS respondersc  

4/13 (30.8%)  5/16 (31.3%)  

a Humira 0.6 mg/kg (maximum of 40 mg) every other week  
b Humira 0.6 mg/kg (maximum of 40 mg) every week  
c In patients receiving concomitant corticosteroids at baseline  
Note: Patients with missing values at Week 52 or who were randomized to receive 
re-induction or maintenance treatment were considered non-responders for Week 52 
endpoints  

 



86 

Additional exploratory efficacy endpoints included clinical response per the Paediatric Ulcerative Colitis 
Activity Index (PUCAI) (defined as a decrease in PUCAI ≥ 20 points from Baseline) and clinical 
remission per PUCAI (defined as PUCAI < 10) at Week 8 and Week 52 (Table 28).  
 

Table 28: Exploratory Endpoints Results per PUCAI 
 Week 8 

Humiraa

Maximum of 160 mg at 
Week 0 / Placebo at Week 1 

N=30 

Humirab,c 

Maximum of 160 mg at 
Week 0 and Week 1 

N=47 

Clinical remission per PUCAI 10/30 (33.3%) 22/47 (46.8%) 

Clinical response per PUCAI 15/30 (50.0%) 32/47 (68.1%) 
 Week 52 

Humirad

Maximum of 40 mg eow 
N=31 

Humirae 

Maximum of 40 mg ew 
N=31 

Clinical remission per PUCAI 
in Week 8 PMS responders 

14/31 (45.2%) 18/31 (58.1%) 

Clinical response per PUCAI 
in Week 8 PMS responders 

18/31 (58.1%) 16/31 (51.6%) 

a Humira 2.4 mg/kg (maximum of 160 mg) at Week 0, placebo at Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2  
b  Humira 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2  
c Not including open-label Induction dose of Humira 2.4 mg/kg (maximum of 160 mg) at 
Week 0 and Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2 
d Humira 0.6 mg/kg (maximum of 40 mg) every other week 
e Humira 0.6 mg/kg (maximum of 40 mg) every week 
Note 1: Both induction groups received 0.6 mg/kg (maximum of 40 mg) at Week 4 and 
Week 6  
Note 2: Patients with missing values at Week 8 were considered as not having met the 
endpoints  
Note 3: Patients with missing values at Week 52 or who were randomized to receive re-
induction or maintenance treatment were considered non-responders for Week 52 
endpoints 

 
 
Of the Humira-treated patients who received re-induction treatment during the maintenance period, 2/6 
(33%) achieved clinical response per FMS at Week 52. 
 
Quality of life 
 
Clinically meaningful improvements from Baseline were observed in IMPACT III and the caregiver Work 
Productivity and Activity Impairment (WPAI) scores for the groups treated with Humira. 
 
Clinically meaningful increases (improvement) from Baseline in height velocity were observed for the 
groups treated with adalimumab, and clinically meaningful increases (improvement) from Baseline in 



87 

Body Mass Index were observed for subjects on the high maintenance dose of maximum 40 mg (0.6 
mg/kg) ew.  
 
Paediatric Uveitis  
 
The safety and efficacy of Humira was assessed in a randomized, double-masked, controlled study of 90 
paediatric patients from 2 to < 18 years of age with active JIA-associated noninfectious anterior uveitis 
who were refractory to at least 12 weeks of methotrexate treatment. Patients received either placebo or 
20 mg adalimumab (if < 30 kg) or 40 mg adalimumab (if ≥ 30 kg) every other week in combination with 
their baseline dose of methotrexate.  
 
The primary endpoint was ‘time to treatment failure’. The criteria determining treatment failure were 
worsening or sustained non-improvement in ocular inflammation, partial improvement with development 
of sustained ocular co-morbidities or worsening of ocular co-morbidities, non-permitted use of 
concomitant medications, and suspension of treatment for an extended period of time. 
 
Clinical Response 
 
Adalimumab significantly delayed the time to treatment failure, as compared to placebo (See Figure 2, 
P < 0.0001 from log rank test).The median time to treatment failure was 24.1 weeks for subjects treated 
with placebo, whereas the median time to treatment failure was not estimable for subjects treated with 
adalimumab because less than one-half of these subjects experienced treatment failure.  Adalimumab 



88 

significantly decreased the risk of treatment failure by 75% relative to placebo, as shown by the hazard 
ratio (HR = 0.25 [95% CI: 0.12, 0.49]). 
 

Figure 2: Kaplan-Meier Curves Summarizing Time to Treatment Failure in the Paediatric Uveitis 

Study 

 

P
R

O
B

A
B

IL
IT

Y
 O

F
 F

A
IL

IN
G

 T
R

E
A

T
M

E
N

T
 

 TIME (WEEKS) 
 Treatment Placebo  Adalimumab 
 Note: P = Placebo (Number at Risk); H = HUMIRA (Number at Risk).

 
 
5.2 Pharmacokinetic properties 
 
Absorption and distribution 
 
Following the administration of 24 mg/m2 (maximum of 40 mg) subcutaneously every other week to 
patients with polyarticular juvenile idiopathic arthritis (JIA) who were 4 to 17 years the mean trough 
steady-state (values measured from Week 20 to 48) serum adalimumab concentration was 5.6 ± 5.6 µg/ml 
(102% CV) for adalimumab without concomitant methotrexate and 10.9 ± 5.2 µg/ml (47.7% CV) with 
concomitant methotrexate. 
 
In patients with polyarticular JIA who were 2 to <4 years old or aged 4 and above weighing <15 kg dosed 
with adalimumab 24 mg/m2, the mean trough steady-state serum adalimumab concentrations was 



89 

6.0 ± 6.1 µg/ml (101% CV) for adalimumab without concomitant methotrexate and 7.9 ± 5.6 µg/ml 
(71.2% CV) with concomitant methotrexate. 
 
Following the administration of 24 mg/m2 (maximum of 40 mg) subcutaneously every other week to 
patients with enthesitis-related arthritis who were 6 to 17 years, the mean trough steady-state (values 
measured at Week 24) serum adalimumab concentrations were 8.8 ± 6.6 μg/ml for adalimumab without 
concomitant methotrexate and 11.8 ± 4.3 μg/ml with concomitant methotrexate. 
 
Following the administration of 0.8 mg/kg (maximum of 40 mg) subcutaneously every other week to 
paediatric patients with chronic plaque psoriasis, the mean ± SD steady-state adalimumab trough 
concentration was approximately 7.4 ± 5.8 µg/ml (79% CV). 
 
Adalimumab exposure in adolescent HS patients was predicted using population pharmacokinetic 
modelling and simulation based on cross-indication pharmacokinetics in other paediatric patients 
(paediatric psoriasis, juvenile idiopathic arthritis, paediatric Crohn’s disease, and enthesitis-related 
arthritis). The recommended adolescent HS dosing schedule is 40 mg every other week. Since exposure to 
adalimumab can be affected by body size, adolescents with higher body weight and inadequate response 
may benefit from receiving the recommended adult dose of 40 mg every week. 
 
In paediatric patients with moderate to severe CD, the open-label adalimumab induction dose was 
160/80 mg or 80/40 mg at Weeks 0 and 2, respectively, dependent on a body weight cut-off of 40 kg. At 
Week 4, patients were randomised 1:1 to either the Standard Dose (40/20 mg eow) or Low Dose (20/10 
mg eow) maintenance treatment groups based on their body weight. The mean (±SD) serum adalimumab 
trough concentrations achieved at Week 4 were 15.7 ± 6.6 g/ml for patients  40 kg (160/80 mg) and 
10.6 ± 6.1 g/ml for patients < 40 kg (80/40 mg). 
 
For patients who stayed on their randomised therapy, the mean (±SD) adalimumab trough concentrations 
at Week 52 were 9.5 ± 5.6 g/ml for the Standard Dose group and 3.5 ± 2.2 g/ml for the Low Dose 
group. The mean trough concentrations were maintained in patients who continued to receive adalimumab 
treatment eow for 52 weeks. For patients who dose escalated from eow to weekly regimen, the mean 
(±SD) serum concentrations of adalimumab at Week 52 were 15.3 ± 11.4 μg/ml (40/20 mg, weekly) and 
6.7 ± 3.5 μg/ml (20/10 mg, weekly). 
 
Adalimumab exposure in paediatric uveitis patients was predicted using population pharmacokinetic 
modelling and simulation based on cross-indication pharmacokinetics in other paediatric patients 
(paediatric psoriasis, juvenile idiopathic arthritis, paediatric Crohn’s disease, and enthesitis-related 
arthritis). No clinical exposure data are available on the use of a loading dose in children < 6 years. The 
predicted exposures indicate that in the absence of methotrexate, a loading dose may lead to an initial 
increase in systemic exposure. 
 
Exposure-response relationship in paediatric population 
On the basis of clinical trial data in patients with JIA (pJIA and ERA), an exposure-response relationship 
was established between plasma concentrations and PedACR 50 response. The apparent adalimumab 
plasma concentration that produces half the maximum probability of PedACR 50 response (EC50) was 
3 μg/ml (95% CI: 1-6 μg/ml).  
 
Exposure-response relationships between adalimumab concentration and efficacy in paediatric patients 
with severe chronic plaque psoriasis were established for PASI 75 and PGA clear or minimal, 
respectively. PASI 75 and PGA clear or minimal increased with increasing adalimumab concentrations, 
both with a similar apparent EC50 of approximately 4.5 μg/ml (95% CI 0.4-47.6 and 1.9-10.5, 
respectively). 
 
Adults 



90 

 
After subcutaneous administration of a single 40 mg dose, absorption and distribution of adalimumab was 
slow, with peak serum concentrations being reached about 5 days after administration. The average 
absolute bioavailability of adalimumab estimated from three studies following a single 40 mg 
subcutaneous dose was 64%. After single intravenous doses ranging from 0.25 to 10 mg/kg, 
concentrations were dose proportional. After doses of 0.5 mg/kg (~40 mg), clearances ranged from 11 to 
15 ml/hour, the distribution volume (Vss) ranged from 5 to 6 litres and the mean terminal phase half-life 
was approximately two weeks. Adalimumab concentrations in the synovial fluid from several rheumatoid 
arthritis patients ranged from 31-96% of those in serum. 
 
Following subcutaneous administration of 40 mg of adalimumab every other week in adult rheumatoid 
arthritis (RA) patients the mean steady-state trough concentrations were approximately 5 g/ml (without 
concomitant methotrexate) and 8 to 9 g/ml (with concomitant methotrexate), respectively. The serum 
adalimumab trough levels at steady-state increased roughly proportionally with dose following 20, 40 and 
80 mg subcutaneous dosing every other week and every week. 
 
In adult patients with psoriasis, the mean steady-state trough concentration was 5 μg/ml during 
adalimumab 40 mg every other week monotherapy treatment. 
 
In adult patients with hidradenitis suppurativa, a dose of 160 mg Humira on Week 0 followed by 80 mg on 
Week 2 achieved serum adalimumab trough concentrations of approximately 7 to 8 μg/ml at Week 2 and 
Week 4.  The mean steady-state trough concentration at Week 12 through Week 36 were approximately 8 
to 10 μg/ml during adalimumab 40 mg every week treatment.   
 
In patients with Crohn’s disease, the loading dose of 80 mg Humira on Week 0 followed by 40 mg Humira 
on Week 2 achieves serum adalimumab trough concentrations of approximately 5.5 g/ml during the 
induction period. A loading dose of 160 mg Humira on Week 0 followed by 80 mg Humira on Week 2 
achieves serum adalimumab trough concentrations of approximately 12 g/ml during the induction period. 
Mean steady-state trough levels of approximately 7 g/ml were observed in Crohn’s disease patients who 
received a maintenance dose of 40 mg Humira every other week. 
 
Following the subcutaneous administration of body weight-based dosing of 0.6 mg/kg (maximum of 
40 mg) every other week to paediatric patients with ulcerative colitis, the mean trough steady-state serum 
adalimumab concentration was 5.01±3.28 µg/ml at Week 52. For patients who received 0.6 mg/kg 
(maximum of 40 mg) every week, the mean (±SD) trough steady-state serum adalimumab concentration 
was 15.7±5.60 μg/ml at Week 52. 
 
In adult patients with uveitis, a loading dose of 80 mg adalimumab on Week 0 followed by 40 mg 
adalimumab every other week starting at Week 1, resulted in mean steady-state concentrations of 
approximately 8 to 10 g/ml. 
 
Population pharmacokinetic and pharmacokinetic/pharmacodynamic modelling and simulation predicted 
comparable adalimumab exposure and efficacy in patients treated with 80 mg every other week when 
compared with 40 mg every week (including adult patients with RA, HS, UC, CD or Ps, patients with 
adolescent HS, and paediatric patients ≥ 40 kg with CD and UC). 
 
Elimination 
 
Population pharmacokinetic analyses with data from over 1,300 RA patients revealed a trend toward 
higher apparent clearance of adalimumab with increasing body weight. After adjustment for weight 
differences, gender and age appeared to have a minimal effect on adalimumab clearance. The serum levels 
of free adalimumab (not bound to anti-adalimumab antibodies, AAA) were observed to be lower in 
patients with measurable AAA.  



91 

 
Hepatic or renal impairment 
 
Humira has not been studied in patients with hepatic or renal impairment. 
 
5.3 Preclinical safety data  
 
Non-clinical data reveal no special hazard for humans based on studies of single dose toxicity, repeated 
dose toxicity, and genotoxicity.   
 
An embryo-foetal developmental toxicity/perinatal developmental study has been performed in 
cynomolgus monkeys at 0, 30 and 100 mg/kg (9-17 monkeys/group) and has revealed no evidence of harm 
to the foetuses due to adalimumab. Neither carcinogenicity studies, nor a standard assessment of fertility 
and postnatal toxicity, were performed with adalimumab due to the lack of appropriate models for an 
antibody with limited cross-reactivity to rodent TNF and to the development of neutralising antibodies in 
rodents. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients  
 
Mannitol 
Citric acid monohydrate 
Sodium citrate 
Sodium dihydrogen phosphate dihydrate 
Disodium phosphate dihydrate 
Sodium chloride 
Polysorbate 80 
Sodium hydroxide 
Water for injections. 
 
6.2 Incompatibilities  
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life  
 
2 years  
 
6.4 Special precautions for storage  
 
Store in a refrigerator (2C – 8C). Do not freeze. Keep the vial in the outer carton in order to protect from 
light.   
 
6.5 Nature and contents of container   
 
Humira 40 mg solution for injection in single-use vial (type I glass), fitted with rubber stoppers, 
aluminium crimps and flip-off seals.  
 
1 Pack of 2 boxes each containing: 



92 

1 vial (0.8 ml sterile solution), 1 empty sterile injection syringe, 1 needle, 1 vial adapter and 2 alcohol 
pads. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER  
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
8. MARKETING AUTHORISATION NUMBER  
 
EU/1/03/256/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation:  8 September 2003 
Date of latest renewal: 8 September 2008 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 



93 

1. NAME OF THE MEDICINAL PRODUCT  
 
Humira 40 mg solution for injection in pre-filled syringe 
Humira 40 mg solution for injection in pre-filled pen 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION  
 
Humira 40 mg solution for injection in pre-filled syringe  
Each 0.8 ml single dose pre-filled syringe contains 40 mg of adalimumab.  
 
Humira 40 mg solution for injection in pre-filled pen 
Each 0.8 ml single dose pre-filled pen contains 40 mg of adalimumab.  
 
Adalimumab is a recombinant human monoclonal antibody produced in Chinese Hamster Ovary cells. 
 
For the full list of excipients, see section 6.1.  
 
 
3. PHARMACEUTICAL FORM  
 
Solution for injection. (injection) 
 
Clear, colourless solution.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications  
 
Rheumatoid arthritis 
 
Humira in combination with methotrexate, is indicated for: 
 
 the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the response 

to disease-modifying anti-rheumatic drugs including methotrexate has been inadequate. 
 the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated 

with methotrexate. 
 
Humira can be given as monotherapy in case of intolerance to methotrexate or when continued treatment 
with methotrexate is inappropriate. 
 
Humira has been shown to reduce the rate of progression of joint damage as measured by X-ray and to 
improve physical function, when given in combination with methotrexate. 
 
Juvenile idiopathic arthritis 
 
Polyarticular juvenile idiopathic arthritis 
 
Humira in combination with methotrexate is indicated for the treatment of active polyarticular juvenile 
idiopathic arthritis, in patients from the age of 2 years who have had an inadequate response to one or 
more disease-modifying anti-rheumatic drugs (DMARDs). Humira can be given as monotherapy in case 



94 

of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate (for the 
efficacy in monotherapy see section 5.1). Humira has not been studied in patients aged less than 2 years. 
 
Enthesitis-related arthritis 
 
Humira is indicated for the treatment of active enthesitis-related arthritis in patients, 6 years of age and 
older, who have had an inadequate response to, or who are intolerant of, conventional therapy (see section 
5.1). 
 
Axial spondyloarthritis  
 
Ankylosing spondylitis (AS) 
 
Humira is indicated for the treatment of adults with severe active ankylosing spondylitis who have had an 
inadequate response to conventional therapy. 
 
Axial spondyloarthritis without radiographic evidence of AS 
 
Humira is indicated for the treatment of adults with severe axial spondyloarthritis without radiographic 
evidence of AS but with objective signs of inflammation by elevated CRP and / or MRI, who have had an 
inadequate response to, or are intolerant to non-steroidal anti-inflammatory drugs (NSAIDs). 
 
Psoriatic arthritis 
 
Humira is indicated for the treatment of active and progressive psoriatic arthritis in adults when the 
response to previous disease-modifying anti-rheumatic drug therapy has been inadequate. Humira has 
been shown to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients 
with polyarticular symmetrical subtypes of the disease (see Section 5.1) and to improve physical function. 
 
Psoriasis 
 
Humira is indicated for the treatment of moderate to severe chronic plaque psoriasis in adult patients who 
are candidates for systemic therapy. 
 
Paediatric plaque psoriasis 
 
Humira is indicated for the treatment of severe chronic plaque psoriasis in children and adolescents from 
4 years of age who have had an inadequate response to or are inappropriate candidates for topical therapy 
and phototherapies. 
 
Hidradenitis suppurativa (HS) 
 
Humira is indicated for the treatment of active moderate to severe hidradenitis suppurativa (acne inversa) 
in adults and adolescents from 12 years of age with an inadequate response to conventional systemic HS 
therapy (see sections 5.1 and 5.2). 
 
Crohn’s disease 
 
Humira is indicated for treatment of moderately to severely active Crohn’s disease, in adult patients who 
have not responded despite a full and adequate course of therapy with a corticosteroid and/or an 
immunosuppressant; or who are intolerant to or have medical contraindications for such therapies.  
 



95 

Paediatric Crohn's disease  
 
Humira is indicated for the treatment of moderately to severely active Crohn's disease in paediatric 
patients (from 6 years of age) who have had an inadequate response to conventional therapy including 
primary nutrition therapy and a corticosteroid and/or an immunomodulator, or who are intolerant to or 
have contraindications for such therapies. 
 
Ulcerative colitis 
 
Humira is indicated for treatment of moderately to severely active ulcerative colitis in adult patients who 
have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine 
(6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such 
therapies.  
 
Paediatric ulcerative colitis 
 
Humira is indicated for the treatment of moderately to severely active ulcerative colitis in paediatric 
patients (from 6 years of age) who have had an inadequate response to conventional therapy including 
corticosteroids and/or 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have 
medical contraindications for such therapies. 
 
Uveitis 
 
Humira is indicated for the treatment of non-infectious intermediate, posterior and panuveitis in adult 
patients who have had an inadequate response to corticosteroids, in patients in need of corticosteroid-
sparing, or in whom corticosteroid treatment is inappropriate. 
 
Paediatric Uveitis 
 
Humira is indicated for the treatment of paediatric chronic non-infectious anterior uveitis in patients from 
2 years of age who have had an inadequate response to or are intolerant to conventional therapy, or in 
whom conventional therapy is inappropriate. 
 
4.2 Posology and method of administration   
 
Humira treatment should be initiated and supervised by specialist physicians experienced in the diagnosis 
and treatment of conditions for which Humira is indicated. Ophthalmologists are advised to consult with 
an appropriate specialist before initiation of treatment with Humira (see section 4.4). Patients treated with 
Humira should be given the Patient Reminder Card. 
 
After proper training in injection technique, patients may self-inject with Humira if their physician 
determines that it is appropriate and with medical follow-up as necessary.  
 
During treatment with Humira, other concomitant therapies (e.g., corticosteroids and/or 
immunomodulatory agents) should be optimised. 
 
Posology 
 
Rheumatoid arthritis 
 
The recommended dose of Humira for adult patients with rheumatoid arthritis is 40 mg adalimumab 
administered every other week as a single dose via subcutaneous injection. Methotrexate should be 
continued during treatment with Humira. 



96 

 
Glucocorticoids, salicylates, non-steroidal anti-inflammatory drugs, or analgesics can be continued during 
treatment with Humira. Regarding combination with disease modifying anti-rheumatic drugs other than 
methotrexate see sections 4.4 and 5.1. 
 
In monotherapy, some patients who experience a decrease in their response to Humira 40 mg every other 
week may benefit from an increase in dosage to 40 mg adalimumab every week or 80 mg every other 
week.  
 
Available data suggest that the clinical response is usually achieved within 12 weeks of treatment. 
Continued therapy should be reconsidered in a patient not responding within this time period. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Dose interruption 
 
There may be a need for dose interruption, for instance before surgery or if a serious infection occurs. 
 
Available data suggest that re-introduction of Humira after discontinuation for 70 days or longer resulted 
in the same magnitudes of clinical response and similar safety profile as before dose interruption. 
 
Ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of AS and psoriatic arthritis 
 
The recommended dose of Humira for patients with ankylosing spondylitis, axial spondyloarthritis without 
radiographic evidence of AS and for patients with psoriatic arthritis is 40 mg adalimumab administered 
every other week as a single dose via subcutaneous injection. 
 
Available data suggest that the clinical response is usually achieved within 12 weeks of treatment. 
Continued therapy should be reconsidered in a patient not responding within this time period. 
 
Psoriasis 
 
The recommended dose of Humira for adult patients is an initial dose of 80 mg administered 
subcutaneously, followed by 40 mg subcutaneously given every other week starting one week after the 
initial dose. 
 
Continued therapy beyond 16 weeks should be carefully reconsidered in a patient not responding within 
this time period. 
 
Beyond 16 weeks, patients with inadequate response to Humira 40 mg every other week may benefit from 
an increase in dosage to 40 mg every week or 80 mg every other week. The benefits and risks of continued 
40 mg weekly or 80 mg every other week therapy should be carefully reconsidered in a patient with an 
inadequate response after the increase in dosage (see section 5.1). If adequate response is achieved with 
40 mg every week or 80 mg every other week, the dosage may subsequently be reduced to 40 mg every 
other week. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Hidradenitis suppurativa 
 



97 

The recommended Humira dose regimen for adult patients with hidradenitis suppurativa (HS) is 160 mg 
initially at Day 1 (given as four 40 mg injections in one day or as two 40 mg injections per day for two 
consecutive days), followed by 80 mg two weeks later at Day 15 (given as two 40 mg injections in one 
day). Two weeks later (Day 29) continue with a dose of 40 mg every week or 80 mg every other week 
(given as two 40 mg injections in one day). Antibiotics may be continued during treatment with Humira if 
necessary. It is recommended that the patient should use a topical antiseptic wash on their HS lesions on a 
daily basis during treatment with Humira. 
 
Continued therapy beyond 12 weeks should be carefully reconsidered in a patient with no improvement 
within this time period.   
 
Should treatment be interrupted, Humira 40 mg every week or 80 mg every other week may be re-
introduced (see section 5.1).  
 
The benefit and risk of continued long-term treatment should be periodically evaluated (see section 5.1). 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Crohn’s disease 
 
The recommended Humira induction dose regimen for adult patients with moderately to severely active 
Crohn’s disease is 80 mg at Week 0 followed by 40 mg at Week 2. In case there is a need for a more rapid 
response to therapy, the regimen 160 mg at Week 0 (given as four 40 mg injections in one day or as two 
40 mg injections per day for two consecutive days), followed by 80 mg at Week 2 (given as two 40 mg 
injections in one day), can be used with the awareness that the risk for adverse events is higher during 
induction. 
 
After induction treatment, the recommended dose is 40 mg every other week via subcutaneous injection. 
Alternatively, if a patient has stopped Humira and signs and symptoms of disease recur, Humira may be 
re-administered. There is little experience from re-administration after more than 8 weeks since the 
previous dose. 
 
During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice 
guidelines. 
 
Some patients who experience decrease in their response to Humira 40 mg every other week may benefit 
from an increase in dosage to 40 mg Humira every week or 80 mg every other week. 
 
Some patients who have not responded by Week 4 may benefit from continued maintenance therapy 
through Week 12. Continued therapy should be carefully reconsidered in a patient not responding within 
this time period. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Ulcerative colitis 
 
The recommended Humira induction dose regimen for adult patients with moderate to severe ulcerative 
colitis is 160 mg at Week 0 (given as four 40 mg injections in one day or as two 40 mg injections per day 



98 

for two consecutive days) and 80 mg at Week 2 (given as two 40 mg injections in one day). After 
induction treatment, the recommended dose is 40 mg every other week via subcutaneous injection.  
 
During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice 
guidelines.  
 
Some patients who experience decrease in their response to Humira 40 mg every other week may benefit 
from an increase in dosage to 40 mg Humira every week or 80 mg every other week. 
 
Available data suggest that clinical response is usually achieved within 2-8 weeks of treatment. Humira 
therapy should not be continued in patients failing to respond within this time period. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Uveitis 
 
The recommended dose of Humira for adult patients with uveitis is an initial dose of 80 mg, followed by 
40 mg given every other week starting one week after the initial dose. There is limited experience in the 
initiation of treatment with Humira alone. Treatment with Humira can be initiated in combination with 
corticosteroids and/or with other non-biologic immunomodulatory agents. Concomitant corticosteroids 
may be tapered in accordance with clinical practice starting two weeks after initiating treatment with 
Humira.    
 
It is recommended that the benefit and risk of continued long-term treatment should be evaluated on a 
yearly basis (see section 5.1).   
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Special populations  
 
Elderly 
 
No dose adjustment is required. 
 
Renal and/or hepatic impairment 
 
Humira has not been studied in these patient populations. No dose recommendations can be made. 
 
Paediatric population 
 
Juvenile idiopathic arthritis 
 
Polyarticular juvenile idiopathic arthritis from 2 years of age 
 
The recommended dose of Humira for patients with polyarticular juvenile idiopathic arthritis from 2 years 
of age is based on body weight (Table 1). Humira is administered every other week via subcutaneous 
injection. 
 

Table 1. Humira Dose for Patients with Polyarticular Juvenile Idiopathic Arthritis  
 



99 

Patient Weight Dosing Regimen 

10 kg to < 30 kg 20 mg every other week 

≥ 30 kg 40 mg every other week 
 
Available data suggest that clinical response is usually achieved within 12 weeks of treatment. Continued 
therapy should be carefully reconsidered in a patient not responding within this time period. 
 
There is no relevant use of Humira in patients aged less than 2 years for this indication. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Enthesitis-related arthritis 
 
The recommended dose of Humira for patients with enthesitis-related arthritis from 6 years of age is based 
on body weight (Table 2). Humira is administered every other week via subcutaneous injection. 
 

Table 2. Humira Dose for Patients with Enthesitis-Related Arthritis 
 

Patient Weight Dosing Regimen 

15 kg to < 30 kg 20 mg every other week 

≥ 30 kg 40 mg every other week 
 
Humira has not been studied in patients with enthesitis-related arthritis aged less than 6 years. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Psoriatic arthritis and axial spondyloarthritis including ankylosing spondylitis 
 
There is no relevant use of Humira in the paediatric population for the indications of ankylosing 
spondylitis and psoriatic arthritis. 
 
Paediatric plaque psoriasis 
 
The recommended Humira dose for patients with plaque psoriasis from 4 to 17 years of age is based on 
body weight (Table 3). Humira is administered via subcutaneous injection.  
 

Table 3. Humira Dose for Paediatric Patients with Plaque Psoriasis 
 

Patient Weight Dosing Regimen 

15 kg to < 30 kg Initial dose of 20 mg, followed by 
20 mg given every other week 

starting one week after the initial 
dose 

≥ 30 kg Initial dose of 40 mg, followed by 
40 mg given every other week 

starting one week after the initial 
dose 

 



100 

Continued therapy beyond 16 weeks should be carefully considered in a patient not responding within this 
time period. 
 
If retreatment with Humira is indicated, the above guidance on dose and treatment duration should be 
followed. 
 
The safety of Humira in paediatric patients with plaque psoriasis has been assessed for a mean of 
13 months. 
 
There is no relevant use of Humira in children aged less than 4 years for this indication. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Adolescent hidradenitis suppurativa (from 12 years of age, weighing at least 30 kg) 
 
There are no clinical trials with Humira in adolescent patients with HS.  The posology of Humira in these 
patients has been determined from pharmacokinetic modelling and simulation (see section 5.2). 
 
The recommended Humira dose is 80 mg at Week 0 followed by 40 mg every other week starting at 
Week 1 via subcutaneous injection.  
 
In adolescent patients with inadequate response to Humira 40 mg every other week, an increase in dosage 
to 40 mg every week or 80 mg every other week may be considered. 
 
Antibiotics may be continued during treatment with Humira if necessary.  It is recommended that the 
patient should use a topical antiseptic wash on their HS lesions on a daily basis during treatment with 
Humira.  
 
Continued therapy beyond 12 weeks should be carefully reconsidered in a patient with no improvement 
within this time period.   
 
Should treatment be interrupted, Humira may be re-introduced as appropriate. 
 
The benefit and risk of continued long-term treatment should be periodically evaluated (see adult data in 
section 5.1) 
 
There is no relevant use of Humira in children aged less than 12 years in this indication. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Paediatric Crohn's disease 
 
The recommended dose of Humira for patients with Crohn’s disease from 6 to 17 years of age is based on 
body weight (Table 4). Humira is administered via subcutaneous injection. 
 

 
 
 
 
 
 



101 

Table 4. Humira Dose for Paediatric Patients with Crohn’s disease 
 

Patient 
Weight 

Induction Dose Maintenance 
Dose 

Starting at 
Week 4

< 40 kg  40 mg at Week 0 and 20 mg at week 2 
 

In case there is a need for a more rapid response to therapy with the 
awareness that the risk for adverse events may be higher with use of the 
higher induction dose, the following dose may be used: 
 80 mg at week 0 and 40 mg at week 2

20 mg every 
other week 

≥ 40 kg  80 mg at week 0 and 40 mg at week 2 
 

In case there is a need for a more rapid response to therapy with the 
awareness that the risk for adverse events may be higher with use of the 
higher induction dose, the following dose may be used: 
 160 mg at week 0 and 80 mg at week 2

40 mg every 
other week 

 
Patients who experience insufficient response may benefit from an increase in dosage: 
 < 40 kg: 20 mg every week 
 ≥ 40 kg: 40 mg every week or 80 mg every other week 
 
Continued therapy should be carefully considered in a subject not responding by week 12. 
 
There is no relevant use of Humira in children aged less than 6 years for this indication. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Paediatric ulcerative colitis  
 
The recommended dose of Humira for patients from 6 to 17 years of age with ulcerative colitis is based on 
body weight (Table 5). Humira is administered via subcutaneous injection.  
 

Table 5. Humira Dose for Paediatric Patients with Ulcerative Colitis  

Patient Weight Induction Dose 
Maintenance Dose 

Starting at Week 4* 
< 40 kg • 80 mg at Week 0 (given as two 40 

mg injections in one day) and 
• 40 mg at Week 2 (given as one 40 

mg injection)

• 40 mg every other week 

≥ 40 kg • 160 mg at Week 0 (given as four 
40 mg injections in one day or 
two 40 mg injections per day for 
two consecutive days) and 

• 80 mg at Week 2 (given as two 40 
mg injections in one day)

• 80 mg every other week 

* Paediatric patients who turn 18 years of age while on Humira should continue their prescribed 
maintenance dose. 

  



102 

Continued therapy beyond 8 weeks should be carefully considered in patients not showing signs of 
response within this time period. 
 
There is no relevant use of Humira in children aged less than 6 years in this indication. 
 
Humira may be available in different strengths and/or presentations depending on the individual treatment 
needs. 
 
Paediatric Uveitis 
 
The recommended dose of Humira for paediatric patients with uveitis from 2 years of age is based on 
body weight (Table 6). Humira is administered via subcutaneous injection. 
 
In paediatric uveitis, there is no experience in the treatment with Humira without concomitant treatment 
with methotrexate. 
 

Table 6. Humira Dose for Paediatric Patients with Uveitis 
 

Patient Weight Dosing Regimen 

< 30 kg 20 mg every other week in 
combination with methotrexate 

≥ 30 kg 40 mg every other week in 
combination with methotrexate 

 
When Humira therapy is initiated, a loading dose of 40 mg for patients < 30 kg or 80 mg for patients ≥ 30 
kg may be administered one week prior to the start of maintenance therapy. No clinical data are available 
on the use of a Humira loading dose in children < 6 years of age (see section 5.2). 
 
There is no relevant use of Humira in children aged less than 2 years in this indication. 
 
It is recommended that the benefit and risk of continued long-term treatment should be evaluated on a 
yearly basis (see section 5.1). 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Method of administration 
 
Humira is administered by subcutaneous injection. Full instructions for use are provided in the package 
leaflet. 
 
Humira is available in other strengths and presentations. 
 
4.3 Contraindications  
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  
 
Active tuberculosis or other severe infections such as sepsis, and opportunistic infections (see section 4.4). 
 
Moderate to severe heart failure (NYHA class III/IV) (see section 4.4). 
 



103 

4.4 Special warnings and precautions for use   
 
Traceability  
 
In order to improve traceability of biological medicinal products, the name and the batch number of the 
administered product should be clearly recorded. 
 
Infections 
 
Patients taking TNF-antagonists are more susceptible to serious infections. Impaired lung function may 
increase the risk for developing infections. Patients must therefore be monitored closely for infections, 
including tuberculosis, before, during and after treatment with Humira. Because the elimination of 
adalimumab may take up to four months, monitoring should be continued throughout this period. 
 
Treatment with Humira should not be initiated in patients with active infections including chronic or 
localised infections until infections are controlled. In patients who have been exposed to tuberculosis and 
patients who have travelled in areas of high risk of tuberculosis or endemic mycoses, such as 
histoplasmosis, coccidioidomycosis, or blastomycosis, the risk and benefits of treatment with Humira 
should be considered prior to initiating therapy (see Other opportunistic infections). 
 
Patients who develop a new infection while undergoing treatment with Humira should be monitored 
closely and undergo a complete diagnostic evaluation. Administration of Humira should be discontinued if 
a patient develops a new serious infection or sepsis, and appropriate antimicrobial or antifungal therapy 
should be initiated until the infection is controlled. Physicians should exercise caution when considering 
the use of Humira in patients with a history of recurring infection or with underlying conditions which 
may predispose patients to infections, including the use of concomitant immunosuppressive medications. 
 
Serious infections 
 
Serious infections, including sepsis, due to bacterial, mycobacterial, invasive fungal, parasitic, viral, or 
other opportunistic infections such as listeriosis, legionellosis and pneumocystis have been reported in 
patients receiving Humira.   
 
Other serious infections seen in clinical trials include pneumonia, pyelonephritis, septic arthritis and 
septicaemia. Hospitalisation or fatal outcomes associated with infections have been reported.  
 
Tuberculosis 
 
Tuberculosis, including reactivation and new onset of tuberculosis, has been reported in patients receiving 
Humira.  Reports included cases of pulmonary and extra-pulmonary (i.e. disseminated) tuberculosis.  
 
Before initiation of therapy with Humira, all patients must be evaluated for both active or inactive 
(“latent”) tuberculosis infection.  This evaluation should include a detailed medical assessment of patient 
history of tuberculosis or possible previous exposure to people with active tuberculosis and previous 
and/or current immunosuppressive therapy.  Appropriate screening tests (i.e. tuberculin skin test and chest 
X-ray) should be performed in all patients (local recommendations may apply).  It is recommended that 
the conduct and results of these tests are recorded in the Patient Reminder Card.  Prescribers are reminded 
of the risk of false negative tuberculin skin test results, especially in patients who are severely ill or 
immunocompromised.  
 
If active tuberculosis is diagnosed, Humira therapy must not be initiated (see section 4.3).  
 
In all situations described below, the benefit/risk balance of therapy should be very carefully considered. 



104 

 
If latent tuberculosis is suspected, a physician with expertise in the treatment of tuberculosis should be 
consulted.   
 
If latent tuberculosis is diagnosed, appropriate treatment must be started with anti-tuberculosis prophylaxis 
treatment before the initiation of Humira, and in accordance with local recommendations.  
 
Use of anti-tuberculosis prophylaxis treatment should also be considered before the initiation of Humira in 
patients with several or significant risk factors for tuberculosis despite a negative test for tuberculosis and 
in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment 
cannot be confirmed.   
 
Despite prophylactic treatment for tuberculosis, cases of reactivated tuberculosis have occurred in patients 
treated with Humira. Some patients who have been successfully treated for active tuberculosis have 
redeveloped tuberculosis while being treated with Humira. 
 
Patients should be instructed to seek medical advice if signs/symptoms suggestive of a tuberculosis 
infection (e.g., persistent cough, wasting/weight loss, low grade fever, listlessness) occur during or after 
therapy with Humira.  
 
Other opportunistic infections 
 
Opportunistic infections, including invasive fungal infections have been observed in patients receiving 
Humira. These infections have not consistently been recognised in patients taking TNF-antagonists and 
this has resulted in delays in appropriate treatment, sometimes resulting in fatal outcomes.  
 
For patients who develop the signs and symptoms such as fever, malaise, weight loss, sweats, cough, 
dyspnoea, and/or pulmonary infiltrates or other serious systemic illness with or without concomitant shock 
an invasive fungal infection should be suspected and administration of Humira should be promptly 
discontinued.  Diagnosis and administration of empiric antifungal therapy in these patients should be made 
in consultation with a physician with expertise in the care of patients with invasive fungal infections.  
 
Hepatitis B reactivation 
 
Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including Humira, who are 
chronic carriers of this virus (i.e. surface antigen positive).  Some cases have had a fatal outcome. Patients 
should be tested for HBV infection before initiating treatment with Humira. For patients who test positive 
for hepatitis B infection, consultation with a physician with expertise in the treatment of hepatitis B is 
recommended. 
 
Carriers of HBV who require treatment with Humira should be closely monitored for signs and symptoms 
of active HBV infection throughout therapy and for several months following termination of therapy. 
Adequate data from treating patients who are carriers of HBV with anti-viral therapy in conjunction with 
TNF-antagonist therapy to prevent HBV reactivation are not available. In patients who develop HBV 
reactivation, Humira should be stopped and effective anti-viral therapy with appropriate supportive 
treatment should be initiated.  
 
Neurological events  
 
TNF-antagonists including Humira have been associated in rare instances with new onset or exacerbation 
of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease 
including multiple sclerosis and optic neuritis, and peripheral demyelinating disease, including Guillain-
Barré syndrome. Prescribers should exercise caution in considering the use of Humira in patients with pre-



105 

existing or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of 
Humira should be considered if any of these disorders develop. There is a known association between 
intermediate uveitis and central demyelinating disorders. Neurologic evaluation should be performed in 
patients with non-infectious intermediate uveitis prior to the initiation of Humira therapy and regularly 
during treatment to assess for pre-existing or developing central demyelinating disorders.  
 
Allergic reactions 
 
Serious allergic reactions associated with Humira were rare during clinical trials. Non-serious allergic 
reactions associated with Humira were uncommon during clinical trials. Reports of serious allergic 
reactions including anaphylaxis have been received following Humira administration. If an anaphylactic 
reaction or other serious allergic reaction occurs, administration of Humira should be discontinued 
immediately and appropriate therapy initiated.  
 
Immunosuppression 
 
In a study of 64 patients with rheumatoid arthritis that were treated with Humira, there was no evidence of 
depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or change in 
enumeration of effector T-, B-, NK-cells, monocyte/macrophages, and neutrophils. 
 
Malignancies and lymphoproliferative disorders 
 
In the controlled portions of clinical trials of TNF-antagonists, more cases of malignancies including 
lymphoma have been observed among patients receiving a TNF-antagonist compared with control 
patients. However, the occurrence was rare. In the post marketing setting, cases of leukaemia have been 
reported in patients treated with a TNF-antagonist. There is an increased background risk for lymphoma 
and leukaemia in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, 
which complicates the risk estimation. With the current knowledge, a possible risk for the development of 
lymphomas, leukaemia, and other malignancies in patients treated with a TNF-antagonist cannot be 
excluded. 
 
Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 22 
years of age) treated with TNF-antagonists (initiation of therapy ≤ 18 years of age), including adalimumab 
in the post marketing setting. Approximately half the cases were lymphomas. The other cases represented 
a variety of different malignancies and included rare malignancies usually associated with 
immunosuppression. A risk for the development of malignancies in children and adolescents treated with 
TNF-antagonists cannot be excluded.  
 
Rare postmarketing cases of hepatosplenic T-cell lymphoma have been identified in patients treated with 
adalimumab. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. 
Some of these hepatosplenic T-cell lymphomas with Humira have occurred in young adult patients on 
concomitant treatment with azathioprine or 6-mercaptopurine used for inflammatory bowel disease. The 
potential risk with the combination of azathioprine or 6-mercaptopurine and Humira should be carefully 
considered. A risk for the development of hepatosplenic T-cell lymphoma in patients treated with Humira 
cannot be excluded (see section 4.8). 
 
No studies have been conducted that include patients with a history of malignancy or in whom treatment 
with Humira is continued following development of malignancy.  Thus, additional caution should be 
exercised in considering Humira treatment of these patients (see section 4.8). 
 
All patients, and in particular patients with a medical history of extensive immunosuppressant therapy or 
psoriasis patients with a history of PUVA treatment should be examined for the presence of non-



106 

melanoma skin cancer prior to and during treatment with Humira.  Melanoma and Merkel cell carcinoma 
have also been reported in patients treated with TNF-antagonists including adalimumab (see section 4.8). 
 
In an exploratory clinical trial evaluating the use of another TNF-antagonist, infliximab, in patients with 
moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, mostly in the lung 
or head and neck, were reported in infliximab-treated patients compared with control patients. All patients 
had a history of heavy smoking. Therefore, caution should be exercised when using any TNF-antagonist in 
COPD patients, as well as in patients with increased risk for malignancy due to heavy smoking. 
 
With current data it is not known if adalimumab treatment influences the risk for developing dysplasia or 
colon cancer.  All patients with ulcerative colitis who are at increased risk for dysplasia or colon 
carcinoma (for example, patients with long-standing ulcerative colitis or primary sclerosing cholangitis), 
or who had a prior history of dysplasia or colon carcinoma should be screened for dysplasia at regular 
intervals before therapy and throughout their disease course. This evaluation should include colonoscopy 
and biopsies per local recommendations. 
 
Haematologic reactions 
 
Rare reports of pancytopenia including aplastic anaemia have been reported with TNF-antagonists.  
Adverse events of the haematologic system, including medically significant cytopenia (e.g. 
thrombocytopenia, leukopenia) have been reported with Humira. All patients should be advised to seek 
immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias (e.g. 
persistent fever, bruising, bleeding, pallor) while on Humira. Discontinuation of Humira therapy should be 
considered in patients with confirmed significant haematologic abnormalities. 
 
Vaccinations  
 
Similar antibody responses to the standard 23-valent pneumococcal vaccine and the influenza trivalent 
virus vaccination were observed in a study in 226 adult subjects with rheumatoid arthritis who were 
treated with adalimumab or placebo. No data are available on the secondary transmission of infection by 
live vaccines in patients receiving Humira.   
 
It is recommended that paediatric patients, if possible, be brought up to date with all immunisations in 
agreement with current immunisation guidelines prior to initiating Humira therapy. 
 
Patients on Humira may receive concurrent vaccinations, except for live vaccines. Administration of live 
vaccines (e.g., BCG vaccine) to infants exposed to adalimumab in utero is not recommended for 5 months 
following the mother’s last adalimumab injection during pregnancy. 
 
Congestive heart failure 
 
In a clinical trial with another TNF-antagonist worsening congestive heart failure and increased mortality 
due to congestive heart failure have been observed. Cases of worsening congestive heart failure have also 
been reported in patients receiving Humira. Humira should be used with caution in patients with mild 
heart failure (NYHA class I/II). Humira is contraindicated in moderate to severe heart failure (see section 
4.3). Treatment with Humira must be discontinued in patients who develop new or worsening symptoms 
of congestive heart failure. 
 
Autoimmune processes 
 
Treatment with Humira may result in the formation of autoimmune antibodies. The impact of long-term 
treatment with Humira on the development of autoimmune diseases is unknown. If a patient develops 
symptoms suggestive of a lupus-like syndrome following treatment with Humira and is positive for 



107 

antibodies against double-stranded DNA, further treatment with Humira should not be given (see section 
4.8). 
 
Concurrent administration of biologic DMARDS or TNF-antagonists 
 
Serious infections were seen in clinical studies with concurrent use of anakinra and another 
TNF-antagonist, etanercept, with no added clinical benefit compared to etanercept alone. Because of the 
nature of the adverse events seen with the combination of etanercept and anakinra therapy, similar 
toxicities may also result from the combination of anakinra and other TNF-antagonists. Therefore, the 
combination of adalimumab and anakinra is not recommended. (See section 4.5). 
 
Concomitant administration of adalimumab with other biologic DMARDS (e.g, anakinra and abatacept) or 
other TNF-antagonists is not recommended based upon the possible increased risk for infections, 
including serious infections and other potential pharmacological interactions. (See section 4.5). 
 
Surgery 
 
There is limited safety experience of surgical procedures in patients treated with Humira. The long half-
life of adalimumab should be taken into consideration if a surgical procedure is planned.  A patient who 
requires surgery while on Humira should be closely monitored for infections, and appropriate actions 
should be taken. There is limited safety experience in patients undergoing arthroplasty while receiving 
Humira.  
 
Small bowel obstruction 
 
Failure to respond to treatment for Crohn’s disease may indicate the presence of fixed fibrotic stricture 
that may require surgical treatment. Available data suggest that Humira does not worsen or cause 
strictures. 
 
Elderly 
 
The frequency of serious infections among Humira treated subjects over 65 years of age (3.7%) was 
higher than for those under 65 years of age (1.5%). Some of those had a fatal outcome. Particular attention 
regarding the risk for infection should be paid when treating the elderly. 
 
Paediatric population 
 
See Vaccinations above. 
 
Excipients with known effects 
 
This medicinal product contains less than 1 mmol of sodium (23 mg) per 0.8 ml dose, i.e. essentially 
‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
Humira has been studied in rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and psoriatic 
arthritis patients taking Humira as monotherapy and those taking concomitant methotrexate.  Antibody 
formation was lower when Humira was given together with methotrexate in comparison with use as 
monotherapy. Administration of Humira without methotrexate resulted in increased formation of 
antibodies, increased clearance and reduced efficacy of adalimumab (see section 5.1).  
 



108 

The combination of Humira and anakinra is not recommended (see section 4.4 “Concurrent administration 
of biologic DMARDS or TNF-antagonists”).  
 
The combination of Humira and abatacept is not recommended (see section 4.4 “Concurrent 
administration of biologic DMARDS or TNF-antagonists”). 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential 
 
Women of childbearing potential should consider the use of adequate contraception to prevent pregnancy 
and continue its use for at least five months after the last Humira treatment. 
 
Pregnancy 
 
A large number (approximately 2100) of prospectively collected pregnancies exposed to adalimumab 
resulting in live birth with known outcomes, including more than 1500 exposed during the first trimester, 
does not indicate an increase in the rate of malformation in the newborn. 
 
In a prospective cohort registry, 257 women with rheumatoid arthritis (RA) or Crohn’s disease (CD) 
treated with adalimumab at least during the first trimester and 120 women with RA or CD not treated with 
adalimumab were enrolled.  The primary endpoint was the birth prevalence of major birth defects. The 
rate of pregnancies ending with at least one live born infant with a major birth defect was 6/69 (8.7%) in 
the adalimumab-treated women with RA and 5/74 (6.8%) in the untreated women with RA (unadjusted 
OR 1.31, 95% CI 0.38-4.52) and 16/152 (10.5%) in the adalimumab-treated women with CD and 3/32 
(9.4%) in the untreated women with CD (unadjusted OR 1.14, 95% CI 0.31-4.16). The adjusted OR 
(accounting for baseline differences) was 1.10 (95% CI 0.45-2.73) with RA and CD combined. There were 
no distinct differences between adalimumab-treated and untreated women for the secondary endpoints 
spontaneous abortions, minor birth defects, preterm delivery, birth size and serious or opportunistic 
infections and no stillbirths or malignancies were reported. The interpretation of data may be impacted due 
to methodological limitations of the study, including small sample size and non-randomized design. 
 
In a developmental toxicity study conducted in monkeys, there was no indication of maternal toxicity, 
embryotoxicity or teratogenicity. Preclinical data on postnatal toxicity of adalimumab are not available 
(see section 5.3). 
 
Due to its inhibition of TNF, adalimumab administered during pregnancy could affect normal immune 
responses in the newborn. Adalimumab should only be used during pregnancy if clearly needed.   
 
Adalimumab may cross the placenta into the serum of infants born to women treated with adalimumab 
during pregnancy. Consequently, these infants may be at increased risk for infection. Administration of 
live vaccines (e.g., BCG vaccine) to infants exposed to adalimumab in utero is not recommended for 
5 months following the mother’s last adalimumab injection during pregnancy. 
 
Breast-feeding 
 
Limited information from the published literature indicates that adalimumab is excreted in breast milk at 
very low concentrations with the presence of adalimumab in human milk at concentrations of 0.1% to 1% 
of the maternal serum level. Given orally, immunoglobulin G proteins undergo intestinal proteolysis and 
have poor bioavailability. No effects on the breastfed newborns/infants are anticipated. Consequently, 
Humira can be used during breastfeeding. 
 
Fertility 



109 

 
Preclinical data on fertility effects of adalimumab are not available. 
 
4.7 Effects on ability to drive and use machines  
 
Humira may have a minor influence on the ability to drive and use machines. Vertigo and visual 
impairment may occur following administration of Humira (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
 
Humira was studied in 9,506 patients in pivotal controlled and open label trials for up to 60 months or 
more. These trials included rheumatoid arthritis patients with short term and long standing disease, 
juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis) as 
well as axial spondyloarthritis (ankylosing spondylitis and axial spondyloarthritis without radiographic 
evidence of AS), psoriatic arthritis, Crohn’s disease, ulcerative colitis, psoriasis, hidradenitis suppurativa 
and uveitis patients. The pivotal controlled studies involved 6,089 patients receiving Humira and 
3,801 patients receiving placebo or active comparator during the controlled period. 
 
The proportion of patients who discontinued treatment due to adverse events during the double-blind, 
controlled portion of pivotal studies was 5.9% for patients taking Humira and 5.4% for control treated 
patients. 
 
The most commonly reported adverse reactions are infections (such as nasopharyngitis, upper respiratory 
tract infection and sinusitis), injection site reactions (erythema, itching, haemorrhage, pain or swelling), 
headache and musculoskeletal pain. 
 
Serious adverse reactions have been reported for Humira. TNF-antagonists, such as Humira affect the 
immune system and their use may affect the body’s defence against infection and cancer. 
Fatal and life-threatening infections (including sepsis, opportunistic infections and TB), HBV reactivation 
and various malignancies (including leukaemia, lymphoma and HSTCL) have also been reported with use 
of Humira. 
 
Serious haematological, neurological and autoimmune reactions have also been reported. These include 
rare reports of pancytopenia, aplastic anaemia, central and peripheral demyelinating events and reports of 
lupus, lupus-related conditions and Stevens-Johnson syndrome. 
 
Paediatric population 
 
In general, the adverse events in paediatric patients were similar in frequency and type to those seen in 
adult patients. 
 
Tabulated list of adverse reactions 
 
The following list of adverse reactions is based on experience from clinical trials and on postmarketing 
experience and are displayed by system organ class and frequency in Table 7 below: very common 
( 1/10); common ( 1/100 to < 1/10); uncommon ( 1/1,000 to < 1/100); rare ( 1/10,000 to < 1/1,000); 
and not known (cannot be estimated from the available data). Within each frequency grouping, 
undesirable effects are presented in order of decreasing seriousness. The highest frequency seen among the 
various indications has been included. An asterisk (*) appears in the SOC column if further information is 
found elsewhere in sections 4.3, 4.4 and 4.8. 
 



110 

Table 7 
Undesirable Effects 

 

System Organ Class Frequency Adverse Reaction 

Infections and 
infestations* 

 

Very common Respiratory tract infections (including lower and 
upper respiratory tract infection, pneumonia, 
sinusitis, pharyngitis, nasopharyngitis and 
pneumonia herpes viral) 

Common 

 

Systemic infections (including sepsis, candidiasis 
and influenza), 
intestinal infections (including gastroenteritis 
viral), 
skin and soft tissue infections (including 
paronychia, cellulitis, impetigo, necrotising 
fasciitis and herpes zoster), 
ear infections, 
oral infections (including herpes simplex, oral 
herpes and tooth infections),  
reproductive tract infections (including 
vulvovaginal mycotic infection),  

urinary tract infections (including 
pyelonephritis), 

fungal infections, 

joint infections 

Uncommon 
 

Neurological infections (including viral 
meningitis), 
opportunistic infections and tuberculosis 
(including coccidioidomycosis, histoplasmosis 
and mycobacterium avium complex infection),  
bacterial infections, 
eye infections, 
diverticulitis1)  

Neoplasms benign, 
malignant and unspecified 
(including cysts and 
polyps)* 

Common 

 

Skin cancer excluding melanoma (including 
basal cell carcinoma and squamous cell 
carcinoma), 

 
benign neoplasm 

Uncommon 
 

Lymphoma**,  
solid organ neoplasm (including breast cancer, 
lung neoplasm and thyroid neoplasm),  
melanoma** 

 Rare Leukaemia1) 

Not known Hepatosplenic T-cell lymphoma1), 



111 

System Organ Class Frequency Adverse Reaction 

Merkel cell carcinoma (neuroendocrine 
carcinoma of the skin)1), 

Kaposi’s sarcoma 

Blood and the lymphatic 
system disorders* 

Very common 

 

Leukopenia (including neutropenia and 
agranulocytosis),  

anaemia 

 
Common Leucocytosis, 

thrombocytopenia
Uncommon Idiopathic thrombocytopenic purpura 

Rare 
 

Pancytopenia 

Immune system disorders* Common 

 

Hypersensitivity, 

allergies (including seasonal allergy) 

Uncommon Sarcoidosis1), 

vasculitis 

Rare Anaphylaxis1) 

Metabolism and nutrition 
disorders 

Very common 

 

Lipids increased 

Common Hypokalaemia,  

uric acid increased,  

blood sodium abnormal, 

hypocalcaemia, 

hyperglycaemia, 

hypophosphatemia, 

dehydration 

Psychiatric disorders Common 

 

Mood alterations (including depression),  

anxiety, 

insomnia 

Nervous system disorders* Very common 

 

Headache 

Common 

 

Paraesthesias (including hypoesthesia), 

migraine, 

nerve root compression 



112 

System Organ Class Frequency Adverse Reaction 

Uncommon 
 

Cerebrovascular accident1), 
tremor, 
neuropathy   

Rare 
 

Multiple sclerosis, 

demyelinating disorders (e.g. optic neuritis, 
Guillain-Barré syndrome) 1) 

Eye disorders Common 

 

Visual impairment, 

conjunctivitis, 

blepharitis, 

eye swelling 

Uncommon Diplopia 

Ear and labyrinth 
disorders  

 

Common 

 

Vertigo 

Uncommon 
 

Deafness,  
tinnitus 

Cardiac disorders*  Common Tachycardia 

Uncommon 

 

Myocardial infarction1), 

arrhythmia, 

congestive heart failure 

Rare 
 

Cardiac arrest 

Vascular disorders Common 

 

Hypertension,  

flushing,  

haematoma 

Uncommon Aortic aneurysm, 
vascular arterial occlusion, 
thrombophlebitis    

Respiratory, thoracic and 
mediastinal disorders* 

Common 

 

Asthma, 

dyspnoea, 

cough 

Uncommon 
 

Pulmonary embolism1), 
interstitial lung disease,  
chronic obstructive pulmonary disease, 
pneumonitis, 



113 

System Organ Class Frequency Adverse Reaction 

pleural effusion1) 

Rare Pulmonary fibrosis1)

Gastrointestinal disorders Very common 

 

Abdominal pain,  

nausea and vomiting 

Common 
 

GI haemorrhage,  
dyspepsia,  
gastroesophageal reflux disease, 
sicca syndrome 

Uncommon 
 

Pancreatitis,  
dysphagia, 
face oedema 

Rare Intestinal perforation1) 

Hepato-biliary disorders* Very Common 

 

Elevated liver enzymes 

Uncommon 
 

Cholecystitis and cholelithiasis, 
hepatic steatosis, 
bilirubin increased 

Rare 
 

Hepatitis 

reactivation of hepatitis B1)  

autoimmune hepatitis1) 

Not known 

 

Liver failure1) 

Skin and subcutaneous 
tissue disorders 

Very Common 

 

Rash (including exfoliative rash) 

Common 
 

Worsening or new onset of psoriasis(including 
palmoplantar pustular psoriasis)1), 
urticaria, 
bruising (including purpura),  
dermatitis (including eczema), 
onychoclasis,  
hyperhidrosis, 
alopecia1), 
pruritus  

Uncommon 
 

Night sweats, 
scar 



114 

System Organ Class Frequency Adverse Reaction 

Rare Erythema multiforme1), 

Stevens-Johnson syndrome1), 

angioedema1), 

cutaneous vasculitis1) 

lichenoid skin reaction1) 

Not known Worsening of symptoms of dermatomyositis1) 

Musculoskeletal and 
connective tissue disorders 

Very common 

 

Musculoskeletal pain 

Common Muscle spasms (including blood creatine 
phosphokinase increased) 

Uncommon Rhabdomyolysis, 
systemic lupus erythematosus 

Rare 
 

Lupus-like syndrome1)

Renal and urinary 
disorders  

Common 

 

Renal impairment, 

haematuria 

Uncommon 
 

Nocturia 

Reproductive system and 
breast disorders 

Uncommon Erectile dysfunction 

General disorders and 
administration site 
conditions* 

Very Common 

 

Injection site reaction (including injection site 
erythema) 

Common 
 

Chest pain,  
oedema, 
pyrexia1) 

Uncommon 
 

Inflammation 

Investigations* Common Coagulation and bleeding disorders (including 
activated partial thromboplastin time prolonged), 

autoantibody test positive (including double 
stranded DNA antibody),  

blood lactate dehydrogenase increased 

Injury, poisoning and 
procedural complications 

Common Impaired healing 

 
* further information is found elsewhere in sections 4.3, 4.4 and 4.8 
** including open label extension studies 



115 

1) including spontaneous reporting data 
 
Hidradenitis suppurativa 
 
The safety profile for patients with HS treated with Humira weekly was consistent with the known safety 
profile of Humira. 
 
Uveitis 
 
The safety profile for patients with uveitis treated with Humira every other week was consistent with the 
known safety profile of Humira. 
 
Description of selected adverse reactions 
 
Injection site reactions   
 
In the pivotal controlled trials in adults and children, 12.9% of patients treated with Humira developed 
injection site reactions (erythema and/or itching, haemorrhage, pain or swelling), compared to 7.2% of 
patients receiving placebo or active control. Injection site reactions generally did not necessitate 
discontinuation of the medicinal product.  
 
Infections  
 
In the pivotal controlled trials in adults and children, the rate of infection was 1.51 per patient year in the 
Humira treated patients and 1.46 per patient year in the placebo and active control-treated patients. The 
infections consisted primarily of nasopharyngitis, upper respiratory tract infection, and sinusitis. Most 
patients continued on Humira after the infection resolved.   
 
The incidence of serious infections was 0.04 per patient year in Humira treated patients and 0.03 per 
patient year in placebo and active control − treated patients.   
 
In controlled and open label adult and paediatric studies with Humira, serious infections (including fatal 
infections, which occurred rarely) have been reported, which include reports of tuberculosis (including 
miliary and extra-pulmonary locations) and invasive opportunistic infections (e.g. disseminated or 
extrapulmonary  histoplasmosis,  blastomycosis, coccidioidomycosis, pneumocystis,  candidiasis, 
aspergillosis and listeriosis). Most of the cases of tuberculosis occurred within the first eight months after 
initiation of therapy and may reflect recrudescence of latent disease. 
 
Malignancies and lymphoproliferative disorders 
 
No malignancies were observed in 249 paediatric patients with an exposure of 655.6 patient years during 
Humira trials in patients with juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and 
enthesitis-related arthritis). In addition, no malignancies were observed in 192 paediatric patients with an 
exposure of 498.1 patient years during Humira trials in paediatric patients with Crohn’s disease. No 
malignancies were observed in 77 paediatric patients with an exposure of 80.0 patient years during a 
Humira trial in paediatric patients with chronic plaque psoriasis. No malignancies were observed in 93 
paediatric patients with an exposure of 65.3 patient years during a Humira trial in paediatric patients with 
ulcerative colitis. No malignancies were observed in 60 paediatric patients with an exposure of 58.4 
patient years during a Humira trial in paediatric patients with uveitis. 
 
During the controlled portions of pivotal Humira trials in adults of at least 12 weeks in duration in patients 
with moderately to severely active rheumatoid arthritis, ankylosing spondylitis, axial spondyloarthritis 
without radiographic evidence of AS,  psoriatic arthritis, psoriasis, hidradenitis suppurativa, Crohn’s 



116 

disease, ulcerative colitis and uveitis, malignancies, other than lymphoma and non-melanoma skin cancer, 
were observed at a rate (95% confidence interval) of 6.8 (4.4, 10.5)  per 1,000 patient-years among 5,291 
Humira treated patients versus a rate of 6.3 (3.4, 11.8)  per 1,000 patient-years among 3,444 control 
patients (median duration of treatment was 4.0 months for Humira and 3.8 months for control-treated 
patients). The rate (95% confidence interval) of non-melanoma skin cancers was 8.8 (6.0, 13.0) per 1,000 
patient-years among Humira-treated patients and 3.2 (1.3, 7.6)  per 1,000 patient-years among control 
patients. Of these skin cancers, squamous cell carcinomas occurred at rates (95% confidence interval) of 
2.7 (1.4, 5.4) per 1,000 patient-years among Humira-treated patients and 0.6 (0.1, 4.5) per 1,000 patient-
years among control patients. The rate (95% confidence interval) of lymphomas was 0.7 (0.2, 2.7) per 
1,000 patient-years among Humira-treated patients and 0.6 (0.1, 4.5)  per 1,000 patient-years among 
control patients. 
 
When combining controlled portions of these trials and ongoing and completed open label extension 
studies with a median duration of approximately 3.3 years including 6,427 patients and over 
26,439 patient-years of therapy, the observed rate of malignancies, other than lymphoma and non-
melanoma skin cancers is approximately 8.5 per 1,000 patient years. The observed rate of non-melanoma 
skin cancers is approximately 9.6 per 1,000 patient years, and the observed rate of lymphomas is 
approximately 1.3 per 1,000 patient years. 
 
In post-marketing experience from January 2003 to December 2010, predominantly in patients with 
rheumatoid arthritis, the reported rate of malignancies is approximately 2.7 per 1,000 patient treatment 
years. The reported rates for non-melanoma skin cancers and lymphomas are approximately 0.2 and 
0.3 per 1,000 patient treatment years, respectively (see section 4.4). 
 
Rare post-marketing cases of hepatosplenic T-cell lymphoma have been reported in patients treated with 
adalimumab (see section 4.4). 
 
Autoantibodies  
 
Patients had serum samples tested for autoantibodies at multiple time points in rheumatoid arthritis studies 
I − V. In these trials, 11.9% of patients treated with Humira and 8.1% of placebo and active 
control − treated patients that had negative baseline anti-nuclear antibody titres reported positive titres at 
Week 24. Two patients out of 3,441 treated with Humira in all rheumatoid arthritis and psoriatic arthritis 
studies developed clinical signs suggestive of new-onset lupus-like syndrome. The patients improved 
following discontinuation of therapy. No patients developed lupus nephritis or central nervous system 
symptoms. 
 
Hepato-biliary events 
 
In controlled Phase 3 trials of Humira in patients with rheumatoid arthritis and psoriatic arthritis with a 
control period duration ranging from 4 to 104 weeks, ALT elevations ≥ 3 x ULN occurred in 3.7% of 
Humira-treated patients and 1.6% of control-treated patients.  
 
In controlled Phase 3 trials of Humira in patients with polyarticular juvenile idiopathic arthritis who were 
4 to 17 years and enthesitis-related arthritis who were 6 to 17 years, ALT elevations ≥ 3 x ULN occurred 
in 6.1% of Humira-treated patients and 1.3% of control-treated patients. Most ALT elevations occurred 
with concomitant methotrexate use. No ALT elevations ≥ 3 x ULN occurred in the Phase 3 trial of Humira 
in patients with polyarticular juvenile idiopathic arthritis who were 2 to <4 years. 
 
In controlled Phase 3 trials of Humira in patients with Crohn’s disease and ulcerative colitis with a control 
period ranging from 4 to 52 weeks. ALT elevations ≥ 3 x ULN occurred in 0.9% of Humira-treated 
patients and 0.9% of controlled-treated patients.  
 



117 

In the Phase 3 trial of Humira in patients with paediatric Crohn’s disease which evaluated efficacy and 
safety of two body weight adjusted maintenance dose regimens following body weight adjusted induction 
therapy up to 52 weeks of treatment, ALT elevations ≥ 3 x ULN occurred in 2.6% (5/192) of patients of 
whom 4 were receiving concomitant immunosuppressants at baseline. 
 
In controlled Phase 3 trials of Humira in patients with plaque Psoriasis with a control period duration 
ranging from 12 to 24 weeks, ALT elevations ≥ 3 x ULN occurred in 1.8% of Humira-treated patients and 
1.8% of control-treated patients.  
 
No ALT elevations ≥3 X ULN occurred in the Phase 3 trial of Humira in paediatric patients with plaque 
psoriasis. 
 
In controlled trials of Humira (initial doses of 160 mg at Week 0 and 80 mg at Week 2, followed by 40 mg 
every week starting at Week 4), in patients with hidradenitis suppurativa with a control period duration 
ranging from 12 to 16 weeks, ALT elevations ≥ 3 x ULN occurred in 0.3% of Humira-treated patients and 
0.6% of control-treated patients. 
 
In controlled trials of Humira (initial doses of 80 mg at Week 0 followed by 40 mg every other week 
starting at Week 1) in adult patients with uveitis up to 80 weeks with a median exposure of 166.5 days and 
105.0 days in Humira-treated and control-treated patients, respectively, ALT elevations ≥ 3 x ULN 
occurred in 2.4% of Humira-treated patients and 2.4% of control-treated patients.  
 
In the controlled Phase 3 trial of Humira in patients with paediatric ulcerative colitis (N=93) which 
evaluated efficacy and safety of a maintenance dose of 0.6 mg/kg (maximum of 40 mg) every other week 
(N=31) and a maintenance dose of 0.6 mg/kg (maximum of 40 mg) every Week (N=32), following body 
weight adjusted induction dosing of 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2 (N=63), or an induction dose of 2.4 mg/kg (maximum of 160 mg) 
at Week 0, placebo at Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2 (N=30), ALT elevations ≥ 
3 X ULN occurred in 1.1% (1/93) of patients. 
 
Across all indications in clinical trials patients with raised ALT were asymptomatic and in most cases 
elevations were transient and resolved on continued treatment.  However, there have also been post-
marketing reports of liver failure as well as less severe liver disorders that may precede liver failure, such 
as hepatitis including autoimmune hepatitis in patients receiving adalimumab. 
 
Concurrent treatment with azathioprine/6-mercaptopurine 
 
In adult Crohn’s disease studies, higher incidences of malignant and serious infection-related adverse 
events were seen with the combination of Humira and azathioprine/6-mercaptopurine compared with 
Humira alone. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important.  It allows 
continued monitoring of the benefit/risk balance of the medicinal product.  Healthcare professionals are 
asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.  
 



118 

4.9 Overdose 
 
No dose-limiting toxicity was observed during clinical trials. The highest dose level evaluated has been 
multiple intravenous doses of 10 mg/kg, which is approximately 15 times the recommended dose.     
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunosuppressants, Tumour Necrosis Factor alpha (TNF-α) inhibitors. 
ATC code: L04AB04 
 
Mechanism of action 
 
Adalimumab binds specifically to TNF and neutralises the biological function of TNF by blocking its 
interaction with the p55 and p75 cell surface TNF receptors.   
 
Adalimumab also modulates biological responses that are induced or regulated by TNF, including changes 
in the levels of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, and ICAM-1 
with an IC50 of 0.1-0.2 nM).  
 
Pharmacodynamic effects  
 
After treatment with Humira, a rapid decrease in levels of acute phase reactants of inflammation 
(C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) and serum cytokines (IL-6) was 
observed, compared to baseline in patients with rheumatoid arthritis. Serum levels of matrix 
metalloproteinases (MMP-1 and MMP-3) that produce tissue remodelling responsible for cartilage 
destruction were also decreased after Humira administration. Patients treated with Humira usually 
experienced improvement in haematological signs of chronic inflammation. 
 
A rapid decrease in CRP levels was also observed in patients with polyarticular juvenile idiopathic 
arthritis, Crohn’s disease, ulcerative colitis and hidradenitis suppurativa after treatment with Humira. In 
patients with Crohn’s disease, a reduction of the number of cells expressing inflammatory markers in the 
colon including a significant reduction of expression of TNFα was seen. Endoscopic studies in intestinal 
mucosa have shown evidence of mucosal healing in adalimumab treated patients. 
 
Clinical efficacy and safety 
 
Rheumatoid arthritis 
 
Humira was evaluated in over 3,000 patients in all rheumatoid arthritis clinical trials. The efficacy and 
safety of Humira were assessed in five randomised, double-blind and well-controlled studies. Some 
patients were treated for up to 120 months duration.  
 
RA study I evaluated 271 patients with moderately to severely active rheumatoid arthritis who were  18 
years old, had failed therapy with at least one disease-modifying, anti rheumatic drug and had insufficient 
efficacy with methotrexate at doses of 12.5 to 25 mg (10 mg if methotrexate-intolerant) every week and 
whose methotrexate dose remained constant at 10 to 25 mg every week. Doses of 20, 40 or 80 mg of 
Humira or placebo were given every other week for 24 weeks.  
 
RA study II evaluated 544 patients with moderately to severely active rheumatoid arthritis who were  18 
years old and had failed therapy with at least one disease-modifying, anti-rheumatic drugs.  Doses of 20 or 



119 

40 mg of Humira were given by subcutaneous injection every other week with placebo on alternative 
weeks or every week for 26 weeks; placebo was given every week for the same duration.  No other 
disease-modifying anti-rheumatic drugs were allowed. 
 
RA study III evaluated 619 patients with moderately to severely active rheumatoid arthritis who were  18 
years old, and who had an ineffective response to methotrexate at doses of 12.5 to 25 mg or have been 
intolerant to 10 mg of methotrexate every week. There were three groups in this study.  The first received 
placebo injections every week for 52 weeks. The second received 20 mg of Humira every week for 
52 weeks. The third group received 40 mg of Humira every other week with placebo injections on 
alternate weeks. Upon completion of the first 52 weeks, 457 patients enrolled in an open-label extension 
phase in which 40 mg of Humira/MTX was administered every other week up to 10 years. 
 
RA study IV primarily assessed safety in 636 patients with moderately to severely active rheumatoid 
arthritis who were  18 years old. Patients were permitted to be either disease-modifying, anti-rheumatic 
drug-naïve or to remain on their pre-existing rheumatologic therapy provided that therapy was stable for a 
minimum of 28 days. These therapies include methotrexate, leflunomide, hydroxychloroquine, 
sulfasalazine and/or gold salts. Patients were randomised to 40 mg of Humira or placebo every other week 
for 24 weeks.   
 
RA study V evaluated 799 methotrexate-naïve, adult patients with moderate to severely active early 
rheumatoid arthritis (mean disease duration less than 9 months). This study evaluated the efficacy of 
Humira 40 mg every other week/methotrexate combination therapy, Humira 40 mg every other week 
monotherapy and methotrexate monotherapy in reducing the signs and symptoms and rate of progression 
of joint damage in rheumatoid arthritis for 104 weeks. Upon completion of the first 104 weeks, 497 
patients enrolled in an open-label extension phase in which 40 mg of Humira was administered every 
other week up to 10 years. 
 
The primary end point in RA studies I, II and III and the secondary endpoint in RA study IV was the 
percent of patients who achieved an ACR 20 response at Week 24 or 26. The primary endpoint in RA 
study V was the percent of patients who achieved an ACR 50 response at Week 52. RA studies III and V 
had an additional primary endpoint at 52 weeks of retardation of disease progression (as detected by X-ray 
results). RA study III also had a primary endpoint of changes in quality of life. 
 
ACR response 
 
The percent of Humira-treated patients achieving ACR 20, 50 and 70 responses was consistent across RA 
studies I, II and III. The results for the 40 mg every other week dose are summarised in Table 8.  
 



120 

Table 8  
ACR Responses in Placebo-Controlled Trials 

(Percent of Patients) 
 

Response RA Study Ia** RA Study IIa** RA Study IIIa** 
 

 Placebo/ 
MTXc 
n=60 

Humirab/ MTXc

n=63 
Placebo 
n=110 

Humirab 
n=113 

Placebo/ 
MTXc 
n=200 

Humirab/ MTXc

n=207 

ACR 20    
 6 months 13.3% 65.1% 19.1% 46.0% 29.5% 63.3%
 12 months NA NA NA NA 24.0% 58.9%
ACR 50    
 6 months 6.7% 52.4% 8.2% 22.1% 9.5% 39.1%
 12 months NA NA NA NA 9.5% 41.5%
ACR 70    
 6 months 3.3% 23.8% 1.8% 12.4% 2.5% 20.8%
 12 months NA NA NA NA 4.5% 23.2%
a RA study I at 24 weeks, RA study II at 26 weeks , and RA study III at 24 and 52 weeks 
b 40 mg Humira administered every other week 
c MTX = methotrexate 
**p < 0.01, Humira versus placebo 

 
In RA studies I-IV, all individual components of the ACR response criteria (number of tender and swollen 
joints, physician and patient assessment of disease activity and pain, disability index (HAQ) scores and 
CRP (mg/dl) values) improved at 24 or 26 weeks compared to placebo. In RA study III, these 
improvements were maintained throughout 52 weeks.  
 
In the open-label extension for RA study III, most patients who were ACR responders maintained 
response when followed for up to 10 years. Of 207 patients who were randomised to Humira 40 mg every 
other week, 114 patients continued on Humira 40 mg every other week for 5 years. Among those, 86 
patients (75.4%) had ACR 20 responses; 72 patients (63.2%) had ACR 50 responses; and 41 patients 
(36%) had ACR 70 responses. Of 207 patients, 81 patients continued on Humira 40 mg every other week 
for 10 years. Among those, 64 patients (79.0%) had ACR 20 responses; 56 patients (69.1%) had ACR 50 
responses; and 43 patients (53.1%) had ACR 70 responses. 
 
In RA study IV, the ACR 20 response of patients treated with Humira plus standard of care was 
statistically significantly better than patients treated with placebo plus standard of care (p < 0.001).   
 
In RA studies I-IV, Humira-treated patients achieved statistically significant ACR 20 and 50 responses 
compared to placebo as early as one to two weeks after initiation of treatment. 
 
In RA study V with early rheumatoid arthritis patients who were methotrexate naïve, combination therapy 
with Humira and methotrexate led to faster and significantly greater ACR responses than methotrexate 
monotherapy and Humira monotherapy at Week 52 and responses were sustained at Week 104 (see Table 
9). 
 



121 

Table 9  
ACR Responses in RA Study V 

(percent of patients) 
 

Response 
MTX 
n=257 

Humira 
n=274 

Humira/MTX 
n=268 

p-valuea p-valueb p-valuec 

ACR 20   
 Week 
52 

62.6% 54.4% 72.8% 0.013 < 0.001 0.043 

 Week 
104 

56.0% 49.3% 69.4% 0.002 < 0.001 0.140 

ACR 50   
 Week 
52 

45.9% 41.2% 61.6% < 0.001 < 0.001 0.317 

 Week 
104 

42.8% 36.9% 59.0% < 0.001 < 0.001 0.162 

ACR 70   
 Week 
52 

27.2% 25.9% 45.5% < 0.001 < 0.001 0.656 

 Week 
104 

28.4% 28.1% 46.6% < 0.001 < 0.001 0.864 

a. p-value is from the pairwise comparison of methotrexate monotherapy and Humira/methotrexate 
combination therapy using the Mann-Whitney U test. 

b. p-value is from the pairwise comparison of Humira monotherapy and Humira/methotrexate 
combination therapy using the Mann-Whitney U test 

c.   p-value is from the pairwise comparison of Humira monotherapy and methotrexate monotherapy 
using the Mann-Whitney U test 

 
In the open-label extension for RA study V, ACR response rates were maintained when followed for up to 
10 years. Of 542 patients who were randomised to Humira 40 mg every other week, 170 patients 
continued on Humira 40 mg every other week for 10 years. Among those, 154 patients (90.6%) had ACR 
20 responses; 127 patients (74.7%) had ACR 50 responses; and 102 patients (60.0%) had ACR 70 
responses. 
 
At Week 52, 42.9% of patients who received Humira/methotrexate combination therapy achieved clinical 
remission (DAS28 (CRP) < 2.6) compared to 20.6% of patients receiving methotrexate monotherapy and 
23.4% of patients receiving Humira monotherapy. Humira/methotrexate combination therapy was 
clinically and statistically superior to methotrexate (p < 0.001) and Humira monotherapy (p < 0.001) in 
achieving a low disease state in patients with recently diagnosed moderate to severe rheumatoid arthritis. 
The response for the two monotherapy arms was similar (p = 0.447).  Of 342 subjects originally 
randomized to Humira monotherapy or Humira/methotrexate combination therapy who entered the open-
label extension study, 171 subjects completed 10 years of Humira treatment. Among those, 109 subjects 
(63.7%) were reported to be in remission at 10 years. 
 
Radiographic response 
 
In RA study III, where Humira treated patients had a mean duration of rheumatoid arthritis of 
approximately 11 years, structural joint damage was assessed radiographically and expressed as change in 
modified Total Sharp Score (TSS) and its components, the erosion score and joint space narrowing score.  
Humira/methotrexate patients demonstrated significantly less radiographic progression than patients 
receiving methotrexate alone at 6 and 12 months (see Table 10).   
 



122 

In the open-label extension of RA Study III, the reduction in rate of progression of structural damage is 
maintained for 8 and 10 years in a subset of patients. At 8 years, 81 of 207 patients originally treated with 
40 mg Humira every other week were evaluated radiographically. Among those, 48 patients showed no 
progression of structural damage defined by a change from baseline in the mTSS of 0.5 or less. At 
10 years, 79 of 207 patients originally treated with 40 mg Humira every other week were evaluated 
radiographically. Among those, 40 patients showed no progression of structural damage defined by a 
change from baseline in the mTSS of 0.5 or less. 
 

Table 10 
 Radiographic Mean Changes Over 12 Months in RA Study III 

 
 Placebo/ 

MTXa 
Humira/MTX 
40 mg every 
other week 

Placebo/MTX-
Humira/MTX (95% 

Confidence 
Intervalb)

p-value 

Total Sharp Score 2.7 0.1 2.6 (1.4, 3.8) < 0.001c 

Erosion score 1.6 0.0 1.6 (0.9, 2.2) < 0.001 
JSNd score 1.0 0.1 0.9 (0.3, 1.4)   0.002 

amethotrexate 
b95% confidence intervals for the differences in change scores between methotrexate and Humira.  
cBased on rank analysis  
dJoint Space Narrowing 
 
In RA study V, structural joint damage was assessed radiographically and expressed as change in modified 
Total Sharp Score (see Table 11). 
 

Table 11 
  Radiographic Mean Changes at Week 52 in RA Study V 

 

 

MTX 
n=257 
(95% 

confidence 
interval) 

Humira 
n=274 
(95% 

confidence 
interval)

Humira/MTX 
n=268 
(95% 

confidence 
interval)

p-valuea p-valueb p-valuec 

Total Sharp 
Score 

5.7 (4.2-7.3) 3.0 (1.7-4.3) 1.3 (0.5-2.1) < 0.001 0.0020 < 0.001 

Erosion score 3.7 (2.7-4.7) 1.7 (1.0-2.4) 0.8 (0.4-1.2) < 0.001 0.0082 < 0.001
JSN score 2.0 (1.2-2.8) 1.3 (0.5-2.1) 0.5 (0-1.0) < 0.001 0.0037 0.151

a p-value is from the pairwise comparison of methotrexate monotherapy and Humira/methotrexate 
combination therapy using the Mann-Whitney U test. 

b p-value is from the pairwise comparison of Humira monotherapy and Humira/methotrexate 
combination therapy using the Mann-Whitney U test  

c p-value is from the pairwise comparison of Humira monotherapy and methotrexate monotherapy 
using the Mann-Whitney U test 

 
Following 52 weeks and 104 weeks of treatment, the percentage of patients without progression (change 
from baseline in modified Total Sharp Score  0.5) was significantly higher with Humira/methotrexate 
combination therapy (63.8% and 61.2% respectively) compared to methotrexate monotherapy (37.4% and 
33.5% respectively, p < 0.001) and Humira monotherapy (50.7%, p < 0.002 and 44.5%, p < 0.001 
respectively).  
 



123 

In the open-label extension of RA study V, the mean change from baseline at Year 10 in the modified 
Total Sharp Score was 10.8, 9.2 and 3.9 in patients originally randomized to methotrexate monotherapy, 
Humira monotherapy and Humira/methotrexate combination therapy, respectively. The corresponding 
proportions of patients with no radiographic progression were 31.3%, 23.7% and 36.7% respectively. 
 
Quality of life and physical function  
 
Health-related quality of life and physical function were assessed using the disability index of the Health 
Assessment Questionnaire (HAQ) in the four original adequate and well-controlled trials, which was a 
pre-specified primary endpoint at Week 52 in RA study III. All doses/schedules of Humira in all four 
studies showed statistically significantly greater improvement in the disability index of the HAQ from 
baseline to Month 6 compared to placebo and in RA study III the same was seen at Week 52. Results from 
the Short Form Health Survey (SF 36) for all doses/schedules of Humira in all four studies support these 
findings, with statistically significant physical component summary (PCS) scores, as well as statistically 
significant pain and vitality domain scores for the 40 mg every other week dose. A statistically significant 
decrease in fatigue as measured by functional assessment of chronic illness therapy (FACIT) scores was 
seen in all three studies in which it was assessed (RA studies I, III, IV). 
 
In RA study III, most subjects who achieved improvement in physical function and continued treatment 
maintained improvement through Week 520 (120 months) of open-label treatment. Improvement in 
quality of life was measured up to Week 156 (36 months) and improvement was maintained through that 
time. 
 
In RA study V, the improvement in the HAQ disability index and the physical component of the SF 36 
showed greater improvement (p < 0.001) for Humira/methotrexate combination therapy versus 
methotrexate monotherapy and Humira monotherapy at Week 52, which was maintained through 
Week 104.  Among the 250 subjects who completed the open-label extension study, improvements in 
physical function were maintained through 10 years of treatment. 
 
Axial spondyloarthritis  
 
Ankylosing spondylitis (AS) 
 
Humira 40 mg every other week was assessed in 393 patients in two randomised, 24 week double − blind, 
placebo − controlled studies in patients with active ankylosing spondylitis (mean baseline score of disease 
activity [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)] was 6.3 in all groups) who have 
had an inadequate response to conventional therapy. Seventy-nine (20.1%) patients were treated 
concomitantly with disease modifying anti − rheumatic drugs, and 37 (9.4%) patients with 
glucocorticoids. The blinded period was followed by an open − label period during which patients 
received Humira 40 mg every other week subcutaneously for up to an additional 28 weeks. Subjects 
(n=215, 54.7%) who failed to achieve ASAS 20 at Weeks 12, or 16 or 20 received early escape open-label 
adalimumab 40 mg every other week subcutaneously and were subsequently treated as non-responders in 
the double-blind statistical analyses. 
 
In the larger AS study I with 315 patients, results showed statistically significant improvement of the signs 
and symptoms of ankylosing spondylitis in patients treated with Humira compared to placebo.  Significant 
response was first observed at Week 2 and maintained through 24 weeks (Table 12).  

 



124 

Table 12 
 Efficacy Responses in Placebo-Controlled AS Study – Study I 

Reduction of Signs and Symptoms 
 

Response Placebo 
N=107 

Humira 
N=208 

ASASa 20 
             Week 2 16% 42%*** 

Week 12 21% 58%*** 
Week 24 19% 51%*** 

ASAS 50 
             Week 2 3% 16%*** 

Week 12 10% 38%*** 
Week 24 11% 35%*** 

ASAS 70 
             Week 2 0% 7%** 

Week 12 5% 23%*** 
Week 24 8% 24%*** 

 
BASDAIb 50 
             Week 2 4% 20%*** 

Week 12  16% 45%*** 
Week 24  15% 42%*** 

***,** Statistically significant at p < 0.001, < 0.01 for all comparisons between Humira and 
placebo at Weeks 2, 12 and  24 
a Assessments in Ankylosing Spondylitis 
b Bath Ankylosing Spondylitis Disease Activity Index 

 
Humira treated patients had significantly greater improvement at Week 12 which was maintained through 
Week 24 in both the SF36 and Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL). 
 
Similar trends (not all statistically significant) were seen in the smaller randomised, double − blind, 
placebo controlled AS study II of 82 adult patients with active ankylosing spondylitis. 
 
Axial spondyloarthritis without radiographic evidence of AS 
 
The safety and efficacy of Humira were assessed in two randomized, double-blind placebo-controlled 
studies in patients with non-radiographic axial spondyloarthritis (nr-axSpA). Study nr-axSpA I evaluated 
patients with active nr-axSpA. Study nr-axSpA II was a treatment withdrawal study in active nr-axSpA 
patients who achieved remission during open-label treatment with Humira. 
 
Study nr-axSpA I 
 
In Study nr-axSpA I, Humira 40 mg every other week was assessed in 185 patients in a randomised, 
12 week double - blind, placebo - controlled study in patients with active nr-axSpA (mean baseline score 
of disease activity [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)] was 6.4 for patients 
treated with Humira and 6.5 for those on placebo) who have had an inadequate response to or intolerance 
to  1 NSAIDs, or a contraindication for NSAIDs. 
 
Thirty-three (18%) patients were treated concomitantly with disease modifying anti-rheumatic drugs, and 
146 (79%) patients with NSAIDs at baseline. The double-blind period was followed by an open-label 
period during which patients receive Humira 40 mg every other week subcutaneously for up to an 



125 

additional 144 weeks. Week 12 results showed statistically significant improvement of the signs and 
symptoms of active nr-axSpA in patients treated with Humira compared to placebo (Table 13). 
 

Table 13 
Efficacy Response in Placebo-Controlled Study nr-axSpA I 

 
Double-Blind 
Response at Week 12 

Placebo 
N=94 

Humira 
N=91 

ASASa 40 15% 36%***
ASAS 20 31% 52%**
ASAS 5/6 6% 31%***
ASAS Partial Remission 5%   16%*
BASDAIb 50 15%    35%**
ASDASc,d,e -0.3 -1.0***
ASDAS Inactive Disease 4% 24%***
hs-CRPd,f,g -0.3 -4.7***
SPARCCh MRI Sacroiliac Jointsd,i -0.6 -3.2**
SPARCC MRI Spined,j -0.2 -1.8**
a Assessment of SpondyloArthritis international Society 
b Bath Ankylosing Spondylitis Disease Activity Index 
c Ankylosing Spondylitis Disease Activity Score 

d mean change from baseline 
e n=91 placebo and n=87 Humira 
f high sensitivity C-Reactive Protein (mg/L) 
g n=73 placebo and n=70 Humira 
h Spondyloarthritis Research Consortium of Canada 
i n=84 placebo and Humira 
j n=82 placebo and n=85 Humira 
***, **, * Statistically significant at p < 0.001, < 0.01, and < 0.05, respectively, for all comparisons 
between Humira and placebo. 
 
In the open-label extension, improvement in the signs and symptoms was maintained with Humira 
therapy through Week 156. 
 
Inhibition of inflammation 
 
Significant improvement of signs of inflammation as measured by hs-CRP and MRI of both Sacroiliac 
Joints and the Spine was maintained in Humira-treated patients through Week 156 and Week 104, 
respectively. 
 
Quality of life and physical function 

 
Health-related quality of life and physical function were assessed using the HAQ-S and the SF-36 
questionnaires. Humira showed statistically significantly greater improvement in the HAQ-S total score 
and the SF-36 Physical Component Score (PCS) from baseline to Week 12 compared to placebo. 
Improvement in health-related quality of life and physical function was maintained during the open-label 
extension through Week 156. 
 
Study nr-axSpA II 
 
673 patients with active nr-axSpA (mean baseline disease activity [BASDAI] was 7.0) who had an 
inadequate response to  2 NSAIDs, or an intolerance to or a contraindication for NSAIDs enrolled into 
the open-label period of Study nr-axSpA II during which they received Humira 40 mg eow for 28 weeks. 



126 

These patients also had objective evidence of inflammation in the sacroiliac joints or spine on MRI or 
elevated hs-CRP. Patients who achieved sustained remission for at least 12 weeks (N=305) (ASDAS < 1.3 
at Weeks 16, 20, 24, and 28) during the open-label period were then randomized to receive either 
continued treatment with Humira 40 mg eow (N=152) or placebo (N=153) for an additional 40 weeks in a 
double-blind, placebo-controlled period (total study duration 68 weeks). Subjects who flared during the 
double-blind period were allowed Humira 40 mg eow rescue therapy for at least 12 weeks. 
 
The primary efficacy endpoint was the proportion of patients with no flare by Week 68 of the study. Flare 
was defined as ASDAS ≥ 2.1 at two consecutive visits four weeks apart. A greater proportion of patients 
on Humira had no disease flare during the double-blind period, when compared with those on placebo 
(70.4% vs. 47.1%, p<0.001) (Figure 1).  

 
Figure 1: Kaplan-Meier Curves Summarizing Time to Flare in  

Study nr-axSpA II 

   
   

   
   

   
   

 P
R

O
B

A
B

IL
IT

Y
 O

F
 N

O
 F

L
A

R
E

 

 TIME (WEEKS) 
                                  Treatment        Placebo     Humira     ∆ Censored

 
Note: P = Placebo (Number at Risk (flared)); A = HUMIRA (Number at Risk (flared)). 
 
Among the 68 patients who flared in the group allocated to treatment withdrawal, 65 completed 12 weeks 
of rescue therapy with Humira, out of which 37 (56.9%) had regained remission (ASDAS < 1.3) after 
12 weeks of restarting the open-label treatment.  
 
By Week 68, patients receiving continuous Humira treatment showed statistically significant greater 
improvement of the signs and symptoms of active nr-axSpA as compared to patients allocated to treatment 
withdrawal during the double-blind period of the study (Table 14). 
 



127 

Table 14 
Efficacy Response in Placebo-Controlled Period for Study nr-axSpA II 
 

Double-Blind 
Response at Week 68 

Placebo 
N=153 

Humira 
N=152 

ASASa,b 20 47.1% 70.4%***
ASASa,b 40 45.8% 65.8%***
ASASa Partial Remission 26.8% 42.1%**
ASDASc Inactive Disease 33.3% 57.2%***
Partial Flared 64.1% 40.8%***
a Assessment of SpondyloArthritis international Society 
b Baseline is defined as open label baseline when patients have active disease. 
c Ankylosing Spondylitis Disease Activity Score 

d Partial flare is defined as ASDAS ≥ 1.3 but < 2.1 at 2 consecutive visits. 
***, ** Statistically significant at p < 0.001 and < 0.01, respectively, for all comparisons between 
Humira and placebo. 

 
Psoriatic arthritis 
 
Humira, 40 mg every other week, was studied in patients with moderately to severely active psoriatic 
arthritis in two placebo-controlled studies, PsA studies I and II.  PsA study I with 24 week duration, 
treated 313 adult patients who had an inadequate response to non-steroidal anti-inflammatory drug therapy 
and of these, approximately 50% were taking methotrexate. PsA study II with 12-week duration, treated 
100 patients who had an inadequate response to DMARD therapy. Upon completion of both studies, 383 
patients enrolled in an open-label extension study, in which 40 mg Humira was administered every other 
week. 
 
There is insufficient evidence of the efficacy of Humira in patients with ankylosing spondylitis-like 
psoriatic arthropathy due to the small number of patients studied.  
 

Table 15 
ACR Response in Placebo-Controlled Psoriatic Arthritis Studies 

(Percent of Patients) 
 

 PsA Study I PsA Study II 

Response 
Placebo 
N=162

Humira 
N=151

Placebo  
N=49

Humira 
N=51 

ACR 20    
 Week 12 14% 58%*** 16% 39%* 
 Week 24 15% 57%*** N/A N/A 
ACR 50    
 Week 12 4% 36%*** 2% 25%*** 
 Week 24 6% 39%*** N/A N/A 
ACR 70    
 Week 12 1% 20%*** 0% 14% * 
 Week 24 1% 23%*** N/A N/A 
*** p < 0.001 for all comparisons between Humira and placebo 
* p < 0.05 for all comparisons between Humira and placebo   
N/A  not applicable 

 
ACR responses in PsA study I were similar with and without concomitant methotrexate therapy. 
ACR responses were maintained in the open-label extension study for up to 136 weeks. 

 



128 

Radiographic changes were assessed in the psoriatic arthritis studies. Radiographs of hands, wrists, and 
feet were obtained at baseline and Week 24 during the double-blind period when patients were on Humira 
or placebo and at Week 48 when all patients were on open-label Humira. A modified Total Sharp Score 
(mTSS), which included distal interphalangeal joints (i.e. not identical to the TSS used for rheumatoid 
arthritis), was used. 
 
Humira treatment reduced the rate of progression of peripheral joint damage compared with placebo 
treatment as measured by change from baseline in mTSS  (mean ± SD) 0.8 ± 2.5 in the placebo group (at 
Week 24) compared with 0.0 ± 1.9; (p< 0.001) in the Humira group (at Week 48). 
 
In subjects treated with Humira with no radiographic progression from baseline to Week 48 (n=102), 84% 
continued to show no radiographic progression through 144 weeks of treatment. 
Humira treated patients demonstrated statistically significant improvement in physical function as assessed 
by HAQ and Short Form Health Survey (SF 36) compared to placebo at Week 24. Improved physical 
function continued during the open label extension up to Week 136. 
 
Psoriasis  
 
The safety and efficacy of Humira were studied in adult patients with chronic plaque psoriasis ( 10% 
BSA involvement and Psoriasis Area and Severity Index (PASI)  12 or  10) who were candidates for 
systemic therapy or phototherapy in randomised, double-blind studies. 73% of patients enrolled in 
Psoriasis Studies I and II had received prior systemic therapy or phototherapy. The safety and efficacy of 
Humira were also studied in adult patients with moderate to severe chronic plaque psoriasis with 
concomitant hand and/or foot psoriasis who were candidates for systemic therapy in a randomised double-
blind study (Psoriasis Study III).   
 
Psoriasis Study I (REVEAL) evaluated 1,212 patients within three treatment periods. In period A, patients 
received placebo or Humira at an initial dose of 80 mg followed by 40 mg every other week starting one 
week after the initial dose. After 16 weeks of therapy, patients who achieved at least a PASI 75 response 
(PASI score improvement of at least 75% relative to baseline), entered period B and received open-label 
40 mg Humira every other week. Patients who maintained PASI 75 response at Week 33 and were 
originally randomised to active therapy in Period A, were re-randomised in period C to receive 40 mg 
Humira every other week or placebo for an additional 19 weeks. Across all treatment groups, the mean 
baseline PASI score was 18.9 and the baseline Physician’s Global Assessment (PGA) score ranged from 
“moderate” (53% of subjects included) to “severe” (41%) to “very severe” (6%). 
 
Psoriasis Study II (CHAMPION) compared the efficacy and safety of Humira versus methotrexate and 
placebo in 271 patients. Patients received placebo, an initial dose of MTX 7.5 mg and thereafter dose 
increases up to Week 12, with a maximum dose of 25 mg or an initial dose of 80 mg Humira followed by 
40 mg every other week (starting one week after the initial dose) for 16 weeks. There are no data available 
comparing Humira and MTX beyond 16 weeks of therapy. Patients receiving MTX who achieved a 
PASI 50 response at Week 8 and/or 12 did not receive further dose increases. Across all treatment 
groups, the mean baseline PASI score was 19.7 and the baseline PGA score ranged from “mild” (<1%) to 
“moderate” (48%) to “severe” (46%) to “very severe” (6%). 
 
Patients participating in all Phase 2 and Phase 3 psoriasis studies were eligible to enrol into an open-label 
extension trial, where Humira was given for at least an additional 108 weeks. 
 
In Psoriasis Studies I and II, a primary endpoint was the proportion of patients who achieved a PASI 75 
response from baseline at Week 16 (see Tables 16 and 17). 
 



129 

Table 16 
Ps Study I (REVEAL)  - Efficacy Results at 16 Weeks 

 
Placebo 
N=398 
n (%) 

Humira 40 mg eow 
N=814 
n (%) 

    PASI 75a 26 (6.5) 578 (70.9)b 
    PASI 100 3 (0.8) 163 (20.0)b 
    PGA: Clear/minimal 17 (4.3) 506 (62.2)b 
a Percent of patients achieving PASI75 response was calculated as centre-
adjusted rate 
b p<0.001, Humira vs. Placebo

 

Table 17 
 Ps Study II (CHAMPION) Efficacy Results at 16 Weeks 

 Placebo 
N=53 
n (%) 

MTX 
N=110 
n (%) 

Humira 40 mg eow 
N=108 
n (%) 

    PASI 75 10 (18.9) 39 (35.5) 86 (79.6) a, b 
    PASI 100 1 (1.9) 8 (7.3) 18 (16.7) c, d 
    PGA: 
Clear/minimal 

6 (11.3) 33 (30.0) 79 (73.1) a, b 

a p<0.001 Humira vs. placebo 
b p<0.001 Humira vs. methotrexate 
c p<0.01 Humira vs. placebo 
d p<0.05 Humira vs. methotrexate

 
In Psoriasis Study I, 28% of patients who were PASI 75 responders and were re-randomised to placebo at 
Week 33 compared to 5% continuing on Humira, p<0.001, experienced “loss of adequate response” (PASI 
score after Week 33 and on or before Week 52 that resulted in a <PASI 50 response relative to baseline 
with a minimum of a 6-point increase in PASI score relative to Week 33). Of the patients who lost 
adequate response after re-randomisation to placebo who then enrolled into the open-label extension trial, 
38% (25/66) and 55% (36/66) regained PASI 75 response after 12 and 24 weeks of re-treatment, 
respectively. 
 
A total of 233 PASI 75 responders at Week 16 and Week 33 received continuous Humira therapy for 
52 weeks in Psoriasis Study I, and continued Humira in the open-label extension trial.  PASI 75 and PGA 
of clear or minimal response rates in these patients were 74.7% and 59.0%, respectively, after an 
additional 108 weeks of open-label therapy (total of 160 weeks). In an analysis in which all patients who 
dropped out of the study for adverse events or lack of efficacy, or who dose-escalated, were considered 
non-responders, PASI 75 and PGA of clear or minimal response rates in these patients were 69.6% and 
55.7%, respectively, after an additional 108 weeks of open-label therapy (total of 160 weeks). 
 
A total of 347 stable responders participated in a withdrawal and retreatment evaluation in an open-label 
extension study. During the withdrawal period, symptoms of psoriasis returned over time with a median 
time to relapse (decline to PGA “moderate” or worse) of approximately 5 months. None of these patients 
experienced rebound during the withdrawal period. A total of 76.5% (218/285) of patients who entered the 
retreatment period had a response of PGA “clear” or “minimal” after 16 weeks of retreatment, irrespective 
of whether they relapsed during withdrawal (69.1%[123/178] and 88.8% [95/107] for patients who 
relapsed and who did not relapse during the withdrawal period, respectively).  A similar safety profile was 
observed during retreatment as before withdrawal. 
 



130 

Significant improvements at Week 16 from baseline compared to placebo (Studies I and II) and MTX 
(Study II) were demonstrated in the DLQI (Dermatology Life Quality Index). In Study I, improvements in 
the physical and mental component summary scores of the SF-36 were also significant compared to 
placebo. 
 
In an open-label extension study, for patients who dose escalated from 40 mg every other week to 40 mg 
weekly due to a PASI response below 50%, 26.4% (92/349) and 37.8% (132/349) of patients achieved 
PASI 75 response at Week 12 and 24, respectively. 
 
Psoriasis Study III (REACH) compared the efficacy and safety of Humira versus placebo in 72 patients 
with moderate to severe chronic plaque psoriasis and hand and/or foot psoriasis. Patients received an 
initial dose of 80 mg Humira followed by 40 mg every other week (starting one week after the initial dose) 
or placebo for 16 weeks. At Week 16, a statistically significantly greater proportion of patients who 
received Humira achieved PGA of 'clear' or 'almost clear' for the hands and/or feet compared to patients 
who received placebo (30.6% versus 4.3%, respectively [P = 0.014]). 
 
Psoriasis Study IV compared efficacy and safety of Humira versus placebo in 217 adult patients with 
moderate to severe nail psoriasis. Patients received an initial dose of 80 mg Humira followed by 40 mg 
every other week (starting one week after the initial dose) or placebo for 26 weeks followed by open-label 
Humira treatment for an additional 26 weeks. Nail psoriasis assessments included the Modified Nail 
Psoriasis Severity Index (mNAPSI), the Physician’s Global Assessment of Fingernail Psoriasis (PGA-F) 
and the Nail Psoriasis Severity Index (NAPSI) (see Table 18). Humira demonstrated a treatment benefit in 
nail psoriasis patients with different extents of skin involvement (BSA≥10% (60% of patients) and 
BSA<10% and ≥5% (40% of patients)).     
 

Table 18 
Ps Study IV Efficacy Results at 16, 26 and 52 Weeks 

Endpoint Week 16 
Placebo-Controlled

Week 26 
Placebo-Controlled

Week 52 
Open-label

Placebo 
N=108 

Humira 
40 mg eow 

N=109

Placebo
N=108 

Humira 
40 mg eow 

N=109

Humira 
40 mg eow  

N=80 
≥ mNAPSI 75 (%) 2.9 26.0a 3.4 46.6a 65.0 
PGA-F clear/minimal and 
≥2-grade improvement (%) 

2.9 29.7a 6.9 48.9a 61.3 

Percent Change in Total 
Fingernail NAPSI (%) 

-7.8 -44.2 a -11.5 -56.2a -72.2 

a p<0.001, Humira vs. placebo  
 
Humira treated patients showed statistically significant improvements at Week 26 compared with placebo 
in the DLQI.  
 
 
Hidradenitis suppurativa 
 
The safety and efficacy of Humira were assessed in randomised, double-blind, placebo-controlled studies 
and an open-label extension study in adult patients with moderate to severe hidradenitis suppurativa (HS) 
who were intolerant, had a contraindication or an inadequate response to at least a 3-month trial of 
systemic antibiotic therapy. The patients in HS-I and HS-II had Hurley Stage II or III disease with at least 
3 abscesses or inflammatory nodules. 
 
Study HS-I (PIONEER I) evaluated 307 patients with 2 treatment periods. In Period A, patients received 
placebo or Humira at an initial dose of 160 mg at Week 0, 80 mg at Week 2, and 40 mg every week 



131 

starting at Week 4 to Week 11. Concomitant antibiotic use was not allowed during the study.  After 
12 weeks of therapy, patients who had received Humira in Period A were re-randomised in Period B to 1 
of 3 treatment groups (Humira 40 mg every week, Humira 40 mg every other week, or placebo from 
Week 12 to Week 35). Patients who had been randomised to placebo in Period A were assigned to receive 
Humira 40 mg every week in Period B. 
 
Study HS-II (PIONEER II) evaluated 326 patients with 2 treatment periods. In Period A, patients received 
placebo or Humira at an initial dose of 160 mg at Week 0 and 80 mg at Week 2 and 40 mg every week 
starting at Week 4 to Week 11. 19.3% of patients had continued baseline oral antibiotic therapy during the 
study. After 12 weeks of therapy, patients who had received Humira in Period A were re-randomised in 
Period B to 1 of 3 treatment groups (Humira 40 mg every week, Humira 40 mg every other week, or 
placebo from Week 12 to Week 35). Patients who had been randomised to placebo in Period A were 
assigned to receive placebo in Period B. 
 
Patients participating in Studies HS-I and HS-II were eligible to enrol into an open-label extension study 
in which Humira 40mg was administered every week. Mean exposure in all adalimumab population was 
762 days. Throughout all 3 studies patients used topical antiseptic wash daily. 
 
Clinical Response 
 
Reduction of inflammatory lesions and prevention of worsening of abscesses and draining fistulas was 
assessed using Hidradenitis Suppurativa Clinical Response (HiSCR; at least a 50% reduction in total 
abscess and inflammatory nodule count with no increase in abscess count and no increase in draining 
fistula count relative to Baseline). Reduction in HS-related skin pain was assessed using a Numeric Rating 
Scale in patients who entered the study with an initial baseline score of 3 or greater on a 11 point scale.  
 
At Week 12, a significantly higher proportion of patients treated with Humira versus placebo achieved 
HiSCR.   At Week 12, a significantly higher proportion of patients in Study HS-II experienced a clinically 
relevant decrease in HS-related skin pain (see Table 19). Patients treated with Humira had significantly 
reduced risk of disease flare during the initial 12 weeks of treatment. 
 

Table 19:  Efficacy Results at 12 Weeks, HS Studies I and II 

 

HS Study I HS Study II 

Placebo
Humira 40 mg 

Weekly Placebo  
Humira 40 mg 

Weekly 

Hidradenitis Suppurativa 
Clinical Response (HiSCR)a   

N = 154 
40 (26.0%) 

N = 153 
64 (41.8%) * 

N=163 
45 (27.6%) 

N=163 
96 (58.9%) *** 

≥30% Reduction in Skin 
Painb 

N = 109 
27 (24.8%)

N = 122 
34 (27.9%)

N=111 
23 (20.7%) 

N=105 
48 (45.7%) ***

* P < 0.05, ***P < 0.001, Humira versus placebo  
a Among all randomised patients. 
b Among patients with baseline HS-related skin pain assessment ≥ 3, based on Numeric Rating 

Scale 0 – 10; 0 = no skin pain, 10 = skin pain as bad as you can imagine.
 
Treatment with Humira 40 mg every week significantly reduced the risk of worsening of abscesses and 
draining fistulas. Approximately twice the proportion of patients in the placebo group in the first 12 weeks 
of Studies HS-I and HS-II, compared with those in the Humira group experienced worsening of abscesses 
(23.0% vs 11.4%, respectively) and draining fistulas (30.0% vs 13.9%, respectively). 
 
Greater improvements at Week 12 from baseline compared to placebo were demonstrated in skin-specific 
health-related quality of life, as measured by the Dermatology Life Quality Index (DLQI; Studies HS-I 



132 

and HS-II), patient global satisfaction with medication treatment as measured by the Treatment 
Satisfaction Questionnaire - medication (TSQM; Studies HS-I and HS-II), and physical health as 
measured by the physical component summary score of the SF-36 (Study HS-I). 
 
In patients with at least a partial response to Humira 40 mg weekly at Week 12, the HiSCR rate at 
Week 36 was higher in patients who continued weekly Humira than in patients in whom dosing frequency 
was reduced to every other week, or in whom treatment was withdrawn (see Table 20).   
 

Table 20:  Proportion of Patientsa Achieving HiSCRb at Weeks 24 and 36 After  
Treatment Reassignment from Weekly Humira at Week 12 

 

Placebo 
(treatment 

withdrawal) 
N = 73 

Humira 40 mg 
every other week 

N = 70 

Humira 40 mg 
weekly 
N = 70 

Week 24 24 (32.9%) 36 (51.4%) 40 (57.1%) 

Week 36 22 (30.1%) 28 (40.0%) 39 (55.7%) 
a Patients with at least a partial response to Humira 40 mg weekly after 

12 weeks of treatment. 
b Patients meeting protocol-specified criteria for loss of response or no 

improvement were required to discontinue from the studies and were 
counted as nonresponders.

   
Among patients who were at least partial responders at Week 12, and who received continuous weekly 
Humira therapy, the HiSCR rate at Week 48 was 68.3% and at Week 96 was 65.1%. Longer term 
treatment with Humira 40 mg weekly for 96 weeks identified no new safety findings. 
 
Among patients whose Humira treatment was withdrawn at Week 12 in Studies HS-I and HS-II, the 
HiSCR rate 12 weeks after re-introduction of Humira 40 mg weekly returned to levels similar to that 
observed before withdrawal (56.0 %). 
 
Crohn’s disease 
 
The safety and efficacy of Humira were assessed in over 1500 patients with moderately to severely active 
Crohn’s disease (Crohn’s Disease Activity Index (CDAI)  220 and  450) in randomised, double-blind, 
placebo-controlled studies. Concomitant stable doses of aminosalicylates, corticosteroids, and/or 
immunomodulatory agents were permitted and 80% of patients continued to receive at least one of these 
medications.  
 
Induction of clinical remission (defined as CDAI < 150) was evaluated in two studies, CD Study I 
(CLASSIC I) and CD Study II (GAIN). In CD Study I, 299 TNF-antagonist naive patients were 
randomised to one of four treatment groups; placebo at Weeks 0 and 2, 160 mg Humira at Week 0 and 
80 mg at Week 2, 80 mg at Week 0 and 40 mg at Week 2, and 40 mg at Week 0 and 20 mg at Week 2. In 
CD Study II, 325 patients who had lost response or were intolerant to infliximab were randomised to 
receive either 160 mg Humira at Week 0 and 80 mg at Week 2 or placebo at Weeks 0 and 2. The primary 
non-responders were excluded from the studies and therefore these patients were not further evaluated. 
 
Maintenance of clinical remission was evaluated in CD study III (CHARM).  In CD Study III, 854 patients 
received open-label 80 mg at Week 0 and 40 mg at Week 2. At Week 4 patients were randomised to 
40 mg every other week, 40 mg every week, or placebo with a total study duration of 56 weeks. Patients in 
clinical response (decrease in CDAI ≥ 70) at Week 4 were stratified and analysed separately from those 
not in clinical response at Week 4. Corticosteroid taper was permitted after Week 8.  
 



133 

CD study I and CD study II induction of remission and response rates are presented in Table 21. 
 

Table 21 
Induction of Clinical Remission and Response 

(Percent of Patients) 

 CD Study I: Infliximab Naive 
Patients 

CD Study II: Infliximab 
Experienced Patients 

 Placebo 
N=74 

Humira 
80/40 mg 

N = 75 

Humira  
160/80 mg 

N=76 

Placebo 
N=166 

Humira  
160/80 mg 

N=159 

Week 4      

Clinical remission 12% 24% 36%* 7% 21%* 

Clinical response (CR-
100) 

24% 37% 49%** 25% 38%** 

All p-values are pairwise comparisons of proportions for Humira versus placebo 
* p < 0.001 
** p < 0.01 

 
Similar remission rates were observed for the 160/80 mg and 80/40 mg induction regimens by Week 8 and 
adverse events were more frequently noted in the 160/80 mg group. 
 
In CD Study III, at Week 4, 58% (499/854) of patients were in clinical response and were assessed in the 
primary analysis. Of those in clinical response at Week 4, 48% had been previously exposed to other TNF-
antagonists. Maintenance of remission and response rates are presented in Table 22.  Clinical remission 
results remained relatively constant irrespective of previous TNF-antagonist exposure. 
 
Disease-related hospitalisations and surgeries were statistically significantly reduced with adalimumab 
compared with placebo at Week 56. 
 



134 

Table 22 
Maintenance of Clinical Remission and Response 

(Percent of Patients) 

 Placebo 40 mg Humira 
every other week 

40 mg Humira
every week 

Week 26 N=170 N=172 N=157 

Clinical remission 17% 40%* 47%* 

Clinical response (CR-100) 27% 52%* 52%* 

Patients in steroid-free remission  
for >=90 daysa 

3% (2/66) 19% (11/58)** 15% (11/74)** 

Week 56 N=170 N=172 N=157 

Clinical remission 12% 36%* 41%* 

Clinical response (CR-100) 17% 41%* 48%* 

Patients in steroid-free remission  
for >=90 daysa 

5% (3/66) 29% (17/58)* 20% (15/74)** 

* p < 0.001 for Humira versus placebo pairwise comparisons   of proportions 
** p < 0.02 for Humira versus placebo pairwise comparisons of proportions 
a Of those receiving corticosteroids at baseline 

 
Among patients who were not in response at Week 4, 43% of Humira maintenance patients responded by 
Week 12 compared to 30% of placebo maintenance patients. These results suggest that some patients who 
have not responded by Week 4 benefit from continued maintenance therapy through Week 12. Therapy 
continued beyond 12 weeks did not result in significantly more responses (see section 4.2).   
 
117/276 patients from CD study I and 272/777 patients from CD studies II and III were followed through 
at least 3 years of open-label adalimumab therapy. 88 and 189 patients, respectively, continued to be in 
clinical remission. Clinical response (CR-100) was maintained in 102 and 233 patients, respectively. 
 
Quality of life 
 
In CD Study I and CD Study II, statistically significant improvement in the disease-specific inflammatory 
bowel disease questionnaire (IBDQ) total score was achieved at Week 4 in patients randomised to Humira 
80/40 mg and 160/80 mg compared to placebo and was seen at Weeks 26 and 56 in CD Study III as well 
among the adalimumab treatment groups compared to the placebo group. 
 
Ulcerative colitis 
 
The safety and efficacy of multiple doses of Humira were assessed in adult patients with moderately to 
severely active ulcerative colitis (Mayo score 6 to 12 with endoscopy subscore of 2 to 3) in randomised, 
double-blind, placebo-controlled studies.  
 
In study UC-I, 390 TNF-antagonist naïve patients were randomised to receive either placebo at Weeks 0 
and 2, 160 mg Humira at Week 0  followed by 80 mg at Week 2,  or 80 mg Humira at Week 0  followed 
by 40 mg at Week 2. After Week 2, patients in both adalimumab arms received 40 mg eow. Clinical 
remission (defined as Mayo score ≤ 2 with no subscore > 1) was assessed at Week 8.  
 
In study UC-II, 248 patients received 160 mg of Humira at Week 0, 80 mg at Week 2 and 40 mg eow 
thereafter, and 246 patients received placebo. Clinical results were assessed for induction of remission at 
Week 8 and for maintenance of remission at Week 52.  
 



135 

Patients induced with 160/80 mg Humira achieved clinical remission versus placebo at Week 8 in 
statistically significantly greater percentages in study UC-I (18% vs. 9% respectively, p=0.031) and study 
UC-II (17% vs. 9% respectively, p=0.019). In study UC-II, among those treated with Humira who were in 
remission at Week 8, 21/41 (51%) were in remission at Week 52. 
 
Results from the overall UC-II study population are shown in Table 23. 
 

Table 23 

Response, Remission and Mucosal Healing in Study UC-II 

(Percent of Patients) 
 Placebo

 
Humira 40 mg  

eow 

Week 52 N=246 N=248 
  Clinical Response  18%   30%* 

  Clinical Remission 9%   17%* 
  Mucosal Healing  15%   25%* 
  Steroid-free remission for ≥ 90 days a  6%  

(N=140) 
     13% * 
(N=150) 

Week 8 and 52 
  Sustained Response  12%   24%** 
  Sustained Remission  4%   8%* 
  Sustained Mucosal Healing  11%  19%* 
Clinical remission is Mayo score ≤ 2 with no subscore > 1; 
Clinical response is decrease from baseline in Mayo score ≥3 points and ≥30% plus a 
decrease in the rectal bleeding subscore [RBS] ≥1 or an absolute RBS of 0 or 1; 
*p<0.05 for Humira vs. placebo pairwise comparison of proportions  
**p<0.001 for Humira vs. placebo pairwise comparison of proportions 
a   Of those receiving corticosteroids at baseline
 
Of those patients who had a response at Week 8, 47% were in response, 29% were in remission, 41% had 
mucosal healing, and 20% were in steroid-free remission for ≥ 90 days at Week 52. 
 
Approximately 40% of patients in study UC-II had failed prior anti-TNF treatment with infliximab. The 
efficacy of adalimumab in those patients was reduced compared to that in anti-TNF naïve patients.  
Among patients who had failed prior anti-TNF treatment, Week 52 remission was achieved by 3% on 
placebo and 10% on adalimumab. 
 
Patients from studies UC-I and UC-II had the option to roll over into an open-label long-term extension 
study (UC III). Following 3 years of adalimumab therapy, 75% (301/402) continued to be in clinical 
remission per partial Mayo score.  
 
Hospitalisation rates 
 
During 52 weeks of studies UC-I and UC-II, lower rates of all-cause hospitalisations and UC-related 
hospitalisations were observed for the adalimumab-treated arm compared to the placebo arm. The number 
of all cause hospitalisations in the adalimumab treatment group was 0.18 per patient year vs. 0.26 per 



136 

patient year in the placebo group and the corresponding figures for UC-related hospitalisations were 0.12 
per patient year vs. 0.22 per patient year. 
 
Quality of life 
 
In study UC-II, treatment with adalimumab resulted in improvements in the Inflammatory Bowel Disease 
Questionnaire (IBDQ) score.    
 
Uveitis 
 
The safety and efficacy of Humira were assessed in adult patients with non-infectious intermediate, 
posterior, and panuveitis, excluding patients with isolated anterior uveitis, in two randomised, double-
masked, placebo-controlled studies (UV I and II). Patients received placebo or Humira at an initial dose of 
80 mg followed by 40 mg every other week starting one week after the initial dose. Concomitant stable 
doses of one non-biologic immunosuppressant were permitted.  
 
Study UV I evaluated 217 patients with active uveitis despite treatment with corticosteroids (oral 
prednisone at a dose of 10 to 60 mg/day). All patients received a 2-week standardised dose of prednisone 
60 mg/day at study entry followed by a mandatory taper schedule, with complete corticosteroid 
discontinuation by Week 15.  
 
Study UV II evaluated 226 patients with inactive uveitis requiring chronic corticosteroid treatment (oral 
prednisone 10 to 35 mg/day) at baseline to control their disease. Patients subsequently underwent a 
mandatory taper schedule, with complete corticosteroid discontinuation by Week 19.  
 
The primary efficacy endpoint in both studies was ´time to treatment failure´. Treatment failure was 
defined by a multi-component outcome based on inflammatory chorioretinal and/or inflammatory retinal 
vascular lesions, anterior chamber (AC) cell grade, vitreous haze (VH) grade and best corrected visual 
acuity (BCVA).  
 
Patients who completed Studies UV I and UV II were eligible to enroll in an uncontrolled long-term 
extension study with an originally planned duration of 78 weeks. Patients were allowed to continue on 
study medication beyond Week 78 until they had access to Humira. 
 
Clinical Response 
 
Results from both studies demonstrated statistically significant reduction of the risk of treatment failure in 
patients treated with Humira versus patients receiving placebo (See Table 24). Both studies demonstrated 
an early and sustained effect of Humira on the treatment failure rate versus placebo (see Figure 2).  
 



137 

Table 24 
Time to Treatment Failure in Studies UV I and UV II 

 
Analysis 
 Treatment 

N Failure 
N (%) 

Median Time to 
Failure (months) 

HRa CI 95% 
for HRa 

P Value b 

Time to Treatment Failure At or After Week 6 in Study UV I   
Primary analysis (ITT)   
 Placebo 107 84 (78.5) 3.0 -- -- -- 
 Adalimumab 110 60 (54.5) 5.6 0.50 0.36, 0.70  < 0.001
Time to Treatment Failure At or After Week 2 in Study UV II 
Primary analysis (ITT)   
 Placebo 111 61 (55.0) 8.3 -- -- -- 
 Adalimumab 115 45 (39.1) NEc 0.57 0.39, 0.84 0.004 

Note:  Treatment failure at or after Week 6 (Study UV I), or at or after Week 2 (Study UV II), was 
counted as event. Drop outs due to reasons other than treatment failure were censored at the time of 
dropping out. 
a HR of adalimumab vs placebo from proportional hazards regression with treatment as factor. 
b 2-sided P value from log rank test. 
c NE = not estimable. Fewer than half of at-risk subjects had an event.  
 
Figure 2: Kaplan-Meier Curves Summarizing Time to Treatment Failure on or after Week 6 (Study 

UV I) or Week 2 (Study UV II) 
 

T
R

E
A

T
M

E
N

T
 F

A
IL

U
R

E
 R

A
T

E
 (

%
) 

 TIME (MONTHS) 
 Study UV I                        Treatment Placebo Adalimumab 



138 

T
R

E
A

T
M

E
N

T
 F

A
IL

U
R

E
 R

A
T

E
 (

%
) 

 TIME (MONTHS)
 Study UV II                       Treatment Placebo Adalimumab 

Note: P# = Placebo (Number of Events/Number at Risk); A# = HUMIRA (Number of 
Events/Number at Risk). 

 
In Study UV I statistically significant differences in favour of adalimumab versus placebo were observed 
for each component of treatment failure.  In Study UV II, statistically significant differences were 
observed for visual acuity only, but the other components were numerically in favour of adalimumab. 
 
Of the 424 subjects included in the uncontrolled long-term extension of Studies UV I and UV II, 60 
subjects were regarded ineligible (e.g. due to deviations or due to complications secondary to diabetic 
retinopathy, due to cataract surgery or vitrectomy) and were excluded from the primary analysis of 
efficacy. Of the 364 remaining patients, 269 evaluable patients (74%) reached 78 weeks of open-label 
adalimumab treatment. Based on the observed data approach, 216 (80.3%) were in quiescence (no active 
inflammatory lesions, AC cell grade ≤ 0.5+, VH grade ≤ 0.5+) with a concomitant steroid dose ≤ 7.5 mg 
per day, and 178 (66.2%) were in steroid-free quiescence. BCVA was either improved or maintained (< 5 
letters deterioration) in 88.6% of the eyes at week 78. Data beyond Week 78 were generally consistent 
with these results but the number of enrolled subjects declined after this time. Overall, among the patients 
who discontinued the study, 18% discontinued due to adverse events, and 8% due to insufficient response 
to adalimumab treatment. 
 
Quality of Life 
 
Patient reported outcomes regarding vision-related functioning were measured in both clinical studies, 
using the NEI VFQ-25. Humira was numerically favoured for the majority of subscores with statistically 
significant mean differences for general vision, ocular pain, near vision, mental health, and total score in 
Study UV I, and for general vision and mental health in Study UV II. Vision related effects were not 
numerically in favour of Humira for colour vision in Study UVI and for colour vision, peripheral vision 
and near vision in Study UV II. 
 
Immunogenicity   
 
Formation of anti-adalimumab antibodies is associated with increased clearance and reduced efficacy of 
adalimumab. There is no apparent correlation between the presence of anti-adalimumab antibodies and the 
occurrence of adverse events. 
 



139 

Patients in rheumatoid arthritis studies I, II and III were tested at multiple time points for anti-adalimumab 
antibodies during the 6 to 12 month period. In the pivotal trials, anti-adalimumab antibodies were 
identified in 5.5% (58/1053) of patients treated with adalimumab, compared to 0.5% (2/370) on placebo.  
In patients not given concomitant methotrexate, the incidence was 12.4%, compared to 0.6% when 
adalimumab was used as add-on to methotrexate.   
 
In patients with polyarticular juvenile idiopathic arthritis who were 4 to 17 years, anti-adalimumab 
antibodies were identified in 15.8% (27/171) of patients treated with adalimumab. In patients not given 
concomitant methotrexate, the incidence was 25.6% (22/86) compared to 5.9% (5/85) when adalimumab 
was used as add-on to methotrexate. In patients with polyarticular juvenile idiopathic arthritis who were 
2 to <4 years old or aged 4 and above weighing <15 kg, anti-adalimumab antibodies were identified in 7% 
(1/15) of patients, and the one patient was receiving concomitant methotrexate. 
 
In patients with enthesitis-related arthritis, anti-adalimumab antibodies were identified in 10.9% (5/46) of 
patients treated with adalimumab. In patients not given concomitant methotrexate, the incidence was 
13.6% (3/22), compared to 8.3% (2/24) when adalimumab was used as add-on to methotrexate. 
 
In patients with psoriatic arthritis, anti-adalimumab antibodies were identified in 38/376 subjects (10%) 
treated with adalimumab. In patients not given concomitant methotrexate, the incidence was 13.5% 
(24/178 subjects), compared to 7% (14 of 198 subjects) when adalimumab was used as add-on to 
methotrexate. 
 
In patients with ankylosing spondylitis anti-adalimumab antibodies were identified in 17/204 subjects 
(8.3%) treated with adalimumab. In patients not given concomitant methotrexate, the incidence was 
16/185 (8.6%), compared to 1/19 (5.3%) when adalimumab was used as add-on to methotrexate. 
 
In patients with non-radiographic axial spondyloarthritis, anti-adalimumab antibodies were identified in 
8/152 subjects (5.3%) who were treated continuously with adalimumab. 
 
In patients with Crohn’s disease, anti-adalimumab antibodies were identified in 7/269 subjects (2.6%) and 
in 19/487 subjects (3.9%) with ulcerative colitis. 
 
In adult patients with psoriasis, anti-adalimumab antibodies were identified in 77/920 subjects (8.4%) 
treated with adalimumab monotherapy. 
 
In adult plaque psoriasis patients on long term adalimumab monotherapy who participated in a withdrawal 
and retreatment study, the rate of antibodies to adalimumab after retreatment (11 of 482 subjects, 2.3%) 
was similar to the rate observed prior to withdrawal (11 of 590 subjects, 1.9%). 
 
In patients with paediatric psoriasis, anti-adalimumab antibodies were identified in 5/38 subjects (13%) 
treated with 0.8 mg/kg adalimumab monotherapy. 
 
In patients with moderate to severe hidradenitis suppurativa, anti-adalimumab antibodies were identified 
in 10/99 subjects (10.1%) treated with adalimumab. 
 
In patients with moderately to severely active paediatric Crohn’s disease, the rate of anti-adalimumab 
antibody development in patients receiving adalimumab was 3.3%.  
 
In adult patients with non-infectious uveitis, anti-adalimumab antibodies were identified in 4.8% (12/249) 
of patients treated with adalimumab. 
 
In patients with moderately to severely active paediatric ulcerative colitis, the rate of anti-adalimumab 
antibody development in patients receiving adalimumab was 3%. 



140 

 
Because immunogenicity analyses are product-specific, comparison of antibody rates with those from 
other products is not appropriate. 
 
Paediatric population 
 
Juvenile idiopathic arthritis (JIA) 
 
Polyarticular juvenile idiopathic arthritis (pJIA) 
 
The safety and efficacy of Humira was assessed in two studies (pJIA I and II) in children with active 
polyarticular or polyarticular course juvenile idiopathic arthritis, who had a variety of JIA onset types 
(most frequently rheumatoid-factor negative or positive polyarthritis and extended oligoarthritis). 
 
pJIA I 
 

The safety and efficacy of Humira were assessed in a multicentre, randomised, double-blind, 
parallel − group study in 171 children (4-17 years old) with polyarticular JIA. In the open-label lead in 
phase (OL LI) patients were stratified into two groups, MTX (methotrexate)-treated or non-MTX-treated. 
Patients who were in the non-MTX stratum were either naïve to or had been withdrawn from MTX at 
least two weeks prior to study drug administration. Patients remained on stable doses of NSAIDs and or 
prednisone ( 0.2 mg /kg/day or 10 mg/day maximum). In the OL LI phase all patients received 24 mg/m2 

up to a maximum of 40 mg Humira every other week for 16 weeks.  The distribution of patients by age 
and minimum, median and maximum dose received during the OL LI phase is presented in Table 25. 
 

Table 25 
Distribution of patients by age and adalimumab dose received during the OL LI phase 

 
Age Group Number of patients at Baseline 

n (%) 
Minimum, median and maximum 
dose

4 to 7 years 31 (18.1) 10, 20 and 25 mg 
8 to 12 years 71 (41.5) 20, 25 and 40 mg 
13 to 17 years 69 (40.4) 25, 40 and 40 mg 

 
Patients demonstrating a Paediatric ACR 30 response at Week 16 were eligible to be randomised into the 
double blind (DB) phase and received either Humira 24 mg/m2 up to a maximum of 40 mg, or placebo 
every other week for an additional 32 weeks or until disease flare. Disease flare criteria were defined as a 
worsening of  30% from baseline in  3 of 6 Paediatric ACR core criteria,  2 active joints, and 
improvement of  30% in no more than 1 of the 6 criteria.  After 32 weeks or at disease flare, patients 
were eligible to enrol into the open label extension phase. 
 



141 

Table 26 
Ped ACR 30 Responses in the JIA study 

 
Stratum MTX Without MTX 
Phase  
OL-LI 16 weeks  

Ped ACR 30 
response (n/N) 

94.1% (80/85) 74.4% (64/86) 

                                                           Efficacy Outcomes
Double Blind 32 weeks Humira /MTX 

(N = 38) 
 

Placebo / MTX 
(N = 37) 

Humira  
(N = 30) 

Placebo 
(N = 28) 

Disease flares at 
the end of 
32 weeksa (n/N) 

36.8% (14/38) 64.9% (24/37)b 43.3% (13/30) 71.4% 
(20/28)c 

Median time to 
disease flare 

>32 weeks 20 weeks >32 weeks 14 weeks 

 

a Ped ACR 30/50/70 responses Week 48 significantly greater than those of placebo treated patients  
b p = 0.015 
c p = 0.031 
 

Amongst those who responded at Week 16 (n=144), the Paediatric ACR 30/50/70/90 responses were 
maintained for up to six years in the OLE phase in patients who received Humira throughout the study. 
Over all 19 subjects, of which 11 of the baseline age group 4 to 12 and 8 of the baseline age group 13 to 
17 years were treated 6 years or longer. 
 
Overall responses were generally better and, fewer patients developed antibodies when treated with the 
combination of Humira and MTX compared to Humira alone. Taking these results into consideration, 
Humira is recommended for use in combination with MTX and for use as monotherapy in patients for 
whom MTX use is not appropriate (see section 4.2). 
 
pJIA II 
 
The safety and efficacy of Humira was assessed in an open-label, multicentre study in 32 children (2 - 
<4 years old or aged 4 and above weighing < 15 kg) with moderately to severely active polyarticular JIA. 
The patients received 24 mg/m2 body surface area (BSA) of Humira up to a maximum of 20 mg every 
other week as a single dose via SC injection for at least 24 weeks. During the study, most subjects used 
concomitant MTX, with fewer reporting use of corticosteroids or NSAIDs. 
 
At Week 12 and Week 24, PedACR30 response was 93.5% and 90.0%, respectively, using the observed 
data approach. The proportions of subjects with PedACR50/70/90 at Week 12 and Week 24 were 
90.3%/61.3%/38.7% and 83.3%/73.3%/36.7%, respectively. Amongst those who responded (Paediatric 
ACR 30) at Week 24 (n=27 out of 30 patients), the Paediatric ACR 30 responses were maintained for up 
to 60 weeks in the OLE phase in patients who received Humira throughout this time period. Overall, 20 
subjects were treated for 60 weeks or longer. 
 
Enthesitis-related arthritis 
 
The safety and efficacy of Humira were assessed in a multicentre, randomised, double-blind study in 46 
paediatric patients (6 to 17 years old) with moderate enthesitis-related arthritis. Patients were randomised 
to receive either 24 mg/m2 body surface area (BSA) of Humira up to a maximum of 40 mg, or placebo 



142 

every other week for 12 weeks. The double-blind period is followed by an open-label (OL) period during 
which patients received 24 mg/m2 BSA of Humira up to a maximum of 40 mg every other week 
subcutaneously for up to an additional 192 weeks. The primary endpoint was the percent change from 
Baseline to Week 12 in the number of active joints with arthritis (swelling not due to deformity or joints 
with loss of motion plus pain and/or tenderness), which was achieved with mean percent decrease of -
62.6% (median percent change -88.9%) in patients in the Humira group compared to -11.6% (median 
percent change -50.0%) in patients in the placebo group. Improvement in number of active joints with 
arthritis was maintained during the OL period through Week 156 for the 26 of 31 (84%) patients in the 
Humira group who remained in the study. Although not statistically significant, the majority of patients 
demonstrated clinical improvement in secondary endpoints such as number of sites of enthesitis, tender 
joint count (TJC), swollen joint count (SJC), Paediatric ACR 50 response, and Paediatric ACR 70 
response. 
 
Paediatric plaque psoriasis  

 
The efficacy of Humira was assessed in a randomised, double-blind, controlled study of 114 paediatric 
patients from 4 years of age with severe chronic plaque psoriasis (as defined by a PGA ≥ 4 or > 20% BSA 
involvement or > 10% BSA involvement with very thick lesions or PASI ≥ 20 or ≥ 10 with clinically 
relevant facial, genital, or hand/ foot involvement) who were inadequately controlled with topical therapy 
and heliotherapy or phototherapy.  
 
Patients received Humira 0.8 mg/kg eow (up to 40 mg), 0.4 mg/kg eow (up to 20 mg), or methotrexate 0.1 
– 0.4 mg/kg weekly (up to 25 mg).   At Week 16, more patients randomised to Humira 0.8 mg/kg had 
positive efficacy responses (e.g., PASI 75) than those randomised to 0.4 mg/kg eow or MTX.   
 

Table 27: Paediatric Plaque Psoriasis Efficacy Results at 16 Weeks 
 

 
MTXa 
N=37 

Humira 0.8 mg/kg eow 
N=38  

 PASI 75b 12 (32.4%) 22 (57.9%) 
 PGA: Clear/minimalc 15 (40.5%) 23 (60.5%) 
a MTX = methotrexate 
b P=0.027, Humira 0.8 mg/kg versus MTX 
c P=0.083, Humira 0.8 mg/kg versus MTX

 
Patients who achieved PASI 75 and PGA clear or minimal were withdrawn from treatment for up to 
36 weeks and monitored for loss of disease control (i.e. a worsening of PGA by at least 2 grades).  Patients 
were then re-treated with adalimumab 0.8 mg/kg eow for an additional 16 weeks and response rates 
observed during retreatment were similar to the previous double-blind period:  PASI 75 response of 78.9% 
(15 of 19 subjects) and PGA clear or minimal of 52.6% (10 of 19 subjects). 
 
In the open label period of the study, PASI 75 and PGA clear or minimal responses were maintained for 
up to an additional 52 weeks with no new safety findings. 
 
Adolescent hidradenitis suppurativa 
 
There are no clinical trials with Humira in adolescent patients with HS. Efficacy of adalimumab for the 
treatment of adolescent patients with HS is predicted based on the demonstrated efficacy and exposure-
response relationship in adult HS patients and the likelihood that the disease course, pathophysiology, and 
drug effects are substantially similar to that of adults at the same exposure levels. Safety of the 
recommended adalimumab dose in the adolescent HS population is based on cross-indication safety 



143 

profile of adalimumab in both adults and paediatric patients at similar or more frequent doses (see section 
5.2). 
 
Paediatric Crohn’s disease  
 

Humira was assessed in a multicentre, randomised, double-blind clinical trial designed to evaluate the 
efficacy and safety of induction and maintenance treatment with doses dependent on body weight 
(< 40 kg or ≥ 40 kg) in 192 paediatric subjects between the ages of 6 and 17 (inclusive) years, with 
moderate to severe Crohn´s disease (CD) defined as Paediatric Crohn's Disease Activity Index (PCDAI) 
score > 30. Subjects had to have failed conventional therapy (including a corticosteroid and/or an 
immunomodulator) for CD. Subjects may also have previously lost response or been intolerant to 
infliximab.  
 
All subjects received open-label induction therapy at a dose based on their Baseline body weight: 160 mg 
at Week 0 and 80 mg at Week 2 for subjects ≥ 40 kg, and 80 mg and 40 mg, respectively, for subjects 
< 40 kg. 
 
At Week 4, subjects were randomised 1:1 based on their body weight at the time to either the Low Dose or 
Standard Dose maintenance regimens as shown in Table 28. 
 

Table 28 
Maintenance regimen

Patient 
Weight 

Low dose Standard 
dose 

< 40 kg 10 mg eow 20 mg eow
≥ 40 kg 20 mg eow 40 mg eow

 
Efficacy results 
 
The primary endpoint of the study was clinical remission at Week 26, defined as PCDAI score  10. 
 
Clinical remission and clinical response (defined as reduction in PCDAI score of at least 15 points from 
Baseline) rates are presented in Table 29. Rates of discontinuation of corticosteroids or 
immunomodulators are presented in Table 30. 
 



144 

Table 29 
Paediatric CD Study 

PCDAI Clinical Remission and Response 
 Standard Dose

40/20 mg eow 
N = 93

Low Dose 
20/10 mg eow 

N = 95

P value* 

Week 26    
   Clinical remission 38.7% 28.4% 0.075 
   Clinical response  59.1% 48.4% 0.073 
Week 52    
   Clinical remission 33.3% 23.2% 0.100 
   Clinical response 41.9% 28.4% 0.038 
* p value for Standard Dose versus Low Dose comparison.

 
Table 30 

Paediatric CD Study 
Discontinuation of Corticosteroids or Immunomodulators and Fistula Remission 

 Standard Dose
40/20 mg eow  

Low Dose 
20/10 mg eow  

P value1 

Discontinued corticosteroids N= 33 N=38  
Week 26 84.8% 65.8% 0.066 
Week 52 69.7% 60.5% 0.420 
Discontinuation of Immunomodulators2 N=60 N=57  
Week 52 30.0% 29.8% 0.983 
Fistula remission3 N=15 N=21  
Week 26 46.7% 38.1% 0.608 
Week 52 40.0% 23.8% 0.303 
1  p value for Standard Dose versus Low Dose comparison. 
2  Immunosuppressant therapy could only be discontinued at or after Week 26 at the 
investigator's discretion if the subject met the clinical response criterion  
3 defined as a closure of all fistulas that were draining at Baseline for at least 2 consecutive 
post-Baseline visits

 
Statistically significant increases (improvement) from Baseline to Week 26 and 52 in Body Mass Index 
and height velocity were observed for both treatment groups. 
 
Statistically and clinically significant improvements from Baseline were also observed in both treatment 
groups for quality of life parameters (including IMPACT III). 
 
One hundred patients (n=100) from the Paediatric CD Study continued in an open-label long-term 
extension study.  After 5 years of adalimumab therapy, 74.0% (37/50) of the 50 patients remaining in the 
study continued to be in clinical remission, and 92.0% (46/50) of patients continued to be in clinical 
response per PCDAI. 
 
Paediatric ulcerative colitis 
 
The safety and efficacy of Humira was assessed in a multicenter, randomized, double-blind, trial in 93 
paediatric patients from 5 to 17 years of age with moderate to severe ulcerative colitis (Mayo score 6 to 12 
with endoscopy subscore of 2 to 3 points, confirmed by centrally read endoscopy) who had an inadequate 
response or intolerance to conventional therapy. Approximately 16% of patients in the study had failed 
prior anti-TNF treatment. Patients who received corticosteroids at enrollment were allowed to taper their 
corticosteroid therapy after Week 4. 



145 

 
In the induction period of the study, 77 patients were randomized 3:2 to receive double-blind treatment 
with Humira at an induction dose of 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2; or an induction dose of 2.4 mg/kg (maximum of 160 mg) at Week 
0, placebo at Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2. Both groups received 0.6 mg/kg 
(maximum of 40 mg) at Week 4 and Week 6. Following an amendment to the study design, the remaining 
16 patients who enrolled in the induction period received open-label treatment with Humira at the 
induction dose of 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 mg/kg (maximum of 
80 mg) at Week 2.  
 
At Week 8, 62 patients who demonstrated clinical response per Partial Mayo Score (PMS; defined as a 
decrease in PMS ≥ 2 points and ≥ 30% from Baseline) were randomized equally to receive double-blind 
maintenance treatment with Humira at a dose of 0.6 mg/kg (maximum of 40 mg) every week (ew), or a 
maintenance dose of 0.6 mg/kg (maximum of 40 mg) every other week (eow). Prior to an amendment to 
the study design, 12 additional patients who demonstrated clinical response per PMS were randomized to 
receive placebo but were not included in the confirmatory analysis of efficacy. 
 
Disease flare was defined as an increase in PMS of at least 3 points (for patients with PMS of 0 to 2 at 
Week 8), at least 2 points (for patients with PMS of 3 to 4 at Week 8), or at least 1 point (for patients with 
PMS of 5 to 6 at Week 8).  
 
Patients who met criteria for disease flare at or after Week 12 were randomized to receive a re-induction 
dose of 2.4 mg/kg (maximum of 160 mg) or a dose of 0.6 mg/kg (maximum of 40 mg) and continued to 
receive their respective maintenance dose regimen afterwards.  
 

Efficacy Results 

 

The co-primary endpoints of the study were clinical remission per PMS (defined as PMS ≤ 2 and no 
individual subscore > 1) at Week 8, and clinical remission per FMS (Full Mayo Score) (defined as a Mayo 
Score ≤ 2 and no individual subscore > 1) at Week 52 in patients who achieved clinical response per PMS 
at Week 8. 
 
Clinical remission rates per PMS at Week 8 for patients in each of the Humira double-
blind induction groups are presented in Table 31.  

Table 31: Clinical Remission per PMS at 8 Weeks  

 

Humiraa 
Maximum of 160 mg at Week 

0 / Placebo at Week 1  
N=30 

Humirab, c  
Maximum of 160 mg at Week 

0 and Week 1  
N=47 

Clinical remission 13/30 (43.3%) 28/47 (59.6%) 



146 

a Humira 2.4 mg/kg (maximum of 160 mg) at Week 0, placebo at Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2  
b Humira 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2  
c Not including open-label Induction dose of Humira 2.4 mg/kg (maximum of 160 mg) at 
Week 0 and Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2 
Note 1: Both induction groups received 0.6 mg/kg (maximum of 40 mg) at Week 4 and 
Week 6  
Note 2: Patients with missing values at Week 8 were considered as not having met the 
endpoint  

 
At Week 52, clinical remission per FMS in Week 8 responders, clinical response per FMS (defined as a 
decrease in Mayo Score ≥ 3 points and ≥ 30% from Baseline) in Week 8 responders, mucosal healing per 
FMS (defined as an Mayo endoscopy score ≤ 1) in Week 8 responders, clinical remission per FMS in 
Week 8 remitters, and the proportion of subjects in corticosteroid-free remission per FMS in Week 8 
responders were assessed in patients who received Humira at the double-blind maximum 40 mg eow (0.6 
mg/kg) and maximum 40 mg ew (0.6 mg/kg) maintenance doses (Table 32).  
 

Table 32: Efficacy Results at 52 Weeks  

Humiraa   
Maximum of 40 mg eow 

N=31 

Humirab   
Maximum of 40 mg ew  

N=31 

Clinical remission in Week 
8 PMS responders  

9/31 (29.0%)  14/31 (45.2%) 

Clinical response in Week 8 
PMS responders  

19/31 (61.3%)  21/31 (67.7%)  

Mucosal healing in 
Week 8 PMS responders  

12/31 (38.7%)  16/31 (51.6%)  

Clinical remission in Week 
8 PMS remitters  

9/21 (42.9%)  10/22 (45.5%)  

Corticosteroid-free 
remission in Week 8 
PMS respondersc  

4/13 (30.8%)  5/16 (31.3%)  

a Humira 0.6 mg/kg (maximum of 40 mg) every other week  
b Humira 0.6 mg/kg (maximum of 40 mg) every week  
c In patients receiving concomitant corticosteroids at baseline  
Note: Patients with missing values at Week 52 or who were randomized to receive 
re-induction or maintenance treatment were considered non-responders for Week 52 
endpoints  

 
Additional exploratory efficacy endpoints included clinical response per the Paediatric Ulcerative Colitis 
Activity Index (PUCAI) (defined as a decrease in PUCAI ≥ 20 points from Baseline) and clinical 
remission per PUCAI (defined as PUCAI < 10) at Week 8 and Week 52 (Table 33).  
 



147 

Table 33: Exploratory Endpoints Results per PUCAI 
 Week 8 

Humiraa

Maximum of 160 mg at 
Week 0 / Placebo at Week 1 

N=30 

Humirab,c 

Maximum of 160 mg at 
Week 0 and Week 1 

N=47 
Clinical remission per PUCAI 10/30 (33.3%) 22/47 (46.8%) 
Clinical response per PUCAI 15/30 (50.0%) 32/47 (68.1%) 
 Week 52 

Humirad

Maximum of 40 mg eow 
N=31

Humirae 

Maximum of 40 mg ew 
N=31 

Clinical remission per PUCAI 
in Week 8 PMS responders 

14/31 (45.2%) 18/31 (58.1%) 

Clinical response per PUCAI 
in Week 8 PMS responders 

18/31 (58.1%) 16/31 (51.6%) 

a Humira 2.4 mg/kg (maximum of 160 mg) at Week 0, placebo at Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2  
b  Humira 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2  
c Not including open-label Induction dose of Humira 2.4 mg/kg (maximum of 160 mg) at 
Week 0 and Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2 
d Humira 0.6 mg/kg (maximum of 40 mg) every other week 
e Humira 0.6 mg/kg (maximum of 40 mg) every week 
Note 1: Both induction groups received 0.6 mg/kg (maximum of 40 mg) at Week 4 and 
Week 6  
Note 2: Patients with missing values at Week 8 were considered as not having met the 
endpoints  
Note 3: Patients with missing values at Week 52 or who were randomized to receive re-
induction or maintenance treatment were considered non-responders for Week 52 
endpoints 

 
Of the Humira-treated patients who received re-induction treatment during the maintenance period, 2/6 
(33%) achieved clinical response per FMS at Week 52. 
 
Quality of life 
 
Clinically meaningful improvements from Baseline were observed in IMPACT III and the caregiver Work 
Productivity and Activity Impairment (WPAI) scores for the groups treated with Humira.  
 
Clinically meaningful increases (improvement) from Baseline in height velocity were observed for the 
groups treated with adalimumab, and clinically meaningful increases (improvement) from Baseline in 
Body Mass Index were observed for subjects on the high maintenance dose of maximum 40 mg (0.6 
mg/kg) ew.  
 
Paediatric Uveitis  
 
The safety and efficacy of Humira was assessed in a randomized, double-masked, controlled study of 90 
paediatric patients from 2 to < 18 years of age with active JIA-associated noninfectious anterior uveitis 
who were refractory to at least 12 weeks of methotrexate treatment.  Patients received either placebo or 
20 mg adalimumab (if < 30 kg) or 40 mg adalimumab (if ≥ 30 kg) every other week in combination with 
their baseline dose of methotrexate.  



148 

 
The primary endpoint was ‘time to treatment failure’. The criteria determining treatment failure were 
worsening or sustained non-improvement in ocular inflammation, partial improvement with development 
of sustained ocular co-morbidities or worsening of ocular co-morbidities, non-permitted use of 
concomitant medications, and suspension of treatment for an extended period of time. 
 
Clinical Response 
 
Adalimumab significantly delayed the time to treatment failure, as compared to placebo (See Figure 3, 
P < 0.0001 from log rank test).The median time to treatment failure was 24.1 weeks for subjects treated 
with placebo, whereas the median time to treatment failure was not estimable for subjects treated with 
adalimumab because less than one-half of these subjects experienced treatment failure.  Adalimumab 
significantly decreased the risk of treatment failure by 75% relative to placebo, as shown by the hazard 
ratio (HR = 0.25 [95% CI:  0.12, 0.49]). 
 

Figure 3: Kaplan-Meier Curves Summarizing Time to Treatment Failure in the Paediatric Uveitis 

Study 

 

P
R

O
B

A
B

IL
IT

Y
 O

F
 F

A
IL

IN
G

 T
R

E
A

T
M

E
N

T
 

 TIME (WEEKS) 
 Treatment Placebo  Adalimumab 
 Note: P = Placebo (Number at Risk); H = HUMIRA (Number at Risk).

 
 
5.2 Pharmacokinetic properties 



149 

 
Absorption and distribution 
 
After subcutaneous administration of a single 40 mg dose, absorption and distribution of adalimumab was 
slow, with peak serum concentrations being reached about 5 days after administration. The average 
absolute bioavailability of adalimumab estimated from three studies following a single 40 mg 
subcutaneous dose was 64%. After single intravenous doses ranging from 0.25 to 10 mg/kg, 
concentrations were dose proportional. After doses of 0.5 mg/kg (~40 mg), clearances ranged from 11 to 
15 ml/hour, the distribution volume (Vss) ranged from 5 to 6 litres and the mean terminal phase half-life 
was approximately two weeks. Adalimumab concentrations in the synovial fluid from several rheumatoid 
arthritis patients ranged from 31-96% of those in serum. 
 
Following subcutaneous administration of 40 mg of adalimumab every other week in adult rheumatoid 
arthritis (RA) patients the mean steady-state trough concentrations were approximately 5 g/ml (without 
concomitant methotrexate) and 8 to 9 g/ml (with concomitant methotrexate), respectively.  The serum 
adalimumab trough levels at steady-state increased roughly proportionally with dose following 20, 40 and 
80 mg subcutaneous dosing every other week and every week. 
 
Following the administration of 24 mg/m2 (maximum of 40 mg) subcutaneously every other week to 
patients with polyarticular juvenile idiopathic arthritis (JIA) who were 4 to 17 years the mean trough 
steady-state (values measured from Week 20 to 48) serum adalimumab concentration was 5.6 ± 5.6 µg/ml 
(102% CV) for adalimumab without concomitant methotrexate and 10.9 ± 5.2 µg/ml (47.7% CV) with 
concomitant methotrexate. 
 
In patients with polyarticular JIA who were 2 to <4 years old or aged 4 and above weighing <15 kg dosed 
with adalimumab 24 mg/m2 , the mean trough steady-state serum adalimumab concentrations was 
6.0 ± 6.1 µg/ml (101% CV) for adalimumab without concomitant methotrexate and 7.9 ± 5.6 µg/ml 
(71.2% CV) with concomitant methotrexate. 
 
Following the administration of 24 mg/m2 (maximum of 40 mg) subcutaneously every other week to 
patients with enthesitis-related arthritis who were 6 to 17 years, the mean trough steady-state (values 
measured at Week 24) serum adalimumab concentrations were 8.8 ± 6.6 μg/ml for adalimumab without 
concomitant methotrexate and 11.8 ± 4.3 μg/ml with concomitant methotrexate. 
 
Following subcutaneous administration of 40 mg of adalimumab every other week in adult non-
radiographic axial spondyloarthritis patients, the mean (±SD) trough steady-state concentration at Week 
68 was 8.0 ± 4.6 g/ml. 
 
In adult patients with psoriasis, the mean steady-state trough concentration was 5 g/ml during 
adalimumab 40 mg every other week monotherapy treatment. 
 
Following the administration of 0.8 mg/kg (maximum of 40 mg) subcutaneously every other week to 
paediatric patients with chronic plaque psoriasis, the mean ± SD steady-state adalimumab trough 
concentration was approximately 7.4 ± 5.8 µg/ml (79% CV). 
 
In adult patients with hidradenitis suppurativa, a dose of 160 mg Humira on Week 0 followed by 80 mg on 
Week 2 achieved serum adalimumab trough concentrations of approximately 7 to 8 μg/ml at Week 2 and 
Week 4.  The mean steady-state trough concentration at Week 12 through Week 36 were approximately 8 
to 10 μg/ml during adalimumab 40 mg every week treatment.   
 
Adalimumab exposure in adolescent HS patients was predicted using population pharmacokinetic 
modelling and simulation based on cross-indication pharmacokinetics in other paediatric patients 



150 

(paediatric psoriasis, juvenile idiopathic arthritis, paediatric Crohn’s disease, and enthesitis-related 
arthritis). The recommended adolescent HS dosing schedule is 40 mg every other week. Since exposure to 
adalimumab can be affected by body size, adolescents with higher body weight and inadequate response 
may benefit from receiving the recommended adult dose of 40 mg every week. 
 
In patients with Crohn’s disease, the loading dose of 80 mg Humira on Week 0 followed by 40 mg Humira 
on Week 2 achieves serum adalimumab trough concentrations of approximately 5.5 g/ml during the 
induction period. A loading dose of 160 mg Humira on Week 0 followed by 80 mg Humira on Week 2 
achieves serum adalimumab trough concentrations of approximately 12 g/ml during the induction period. 
Mean steady-state trough levels of approximately 7 g/ml were observed in Crohn’s disease patients who 
received a maintenance dose of 40 mg Humira every other week. 
 
In paediatric patients with moderate to severe CD, the open-label adalimumab induction dose was 
160/80 mg or 80/40 mg at Weeks 0 and 2, respectively, dependent on a body weight cut-off of 40 kg.  At 
Week 4, patients were randomised 1:1 to either the Standard Dose (40/20 mg eow) or Low Dose 
(20/10 mg eow) maintenance treatment groups based on their body weight. The mean (±SD) serum 
adalimumab trough concentrations achieved at Week 4 were 15.7±6.6 g/ml for patients ≥ 40 kg 
(160/80 mg) and 10.6±6.1 g/ml for patients < 40 kg (80/40 mg).  
 
For patients who stayed on their randomised therapy, the mean (±SD) adalimumab trough concentrations 
at Week 52 were 9.5±5.6g/ml for the Standard Dose group and 3.5±2.2 g/ml for the Low Dose group.  
The mean trough concentrations were maintained in patients who continued to receive adalimumab 
treatment eow for 52 weeks. For patients who dose escalated from eow to weekly regimen, the mean 
(±SD) serum concentrations of adalimumab at Week 52 were 15.3±11.4 μg/ml (40/20 mg, weekly) and 
6.7±3.5 μg/ml (20/10 mg, weekly). 
 
In patients with ulcerative colitis, a loading dose of 160 mg Humira on Week 0 followed by 80 mg Humira 
on Week 2 achieves serum adalimumab trough concentrations of approximately 12 g/ml during the 
induction period.  Mean steady-state trough levels of approximately 8 g/ml were observed in ulcerative 
colitis patients who received a maintenance dose of 40 mg Humira every other week.  
 
Following the subcutaneous administration of body weight-based dosing of 0.6 mg/kg (maximum of 
40 mg) every other week to paediatric patients with ulcerative colitis, the mean trough steady-state serum 
adalimumab concentration was 5.01±3.28 µg/ml at Week 52. For patients who received 0.6 mg/kg 
(maximum of 40 mg) every week, the mean (±SD) trough steady-state serum adalimumab concentration 
was 15.7±5.60 μg/ml at Week 52. 
 
In adult patients with uveitis, a loading dose of 80 mg adalimumab on Week 0 followed by 40 mg 
adalimumab every other week starting at Week 1, resulted in mean steady-state concentrations of 
approximately 8 to 10 g/ml. 
 
Adalimumab exposure in paediatric uveitis patients was predicted using population pharmacokinetic 
modelling and simulation based on cross-indication pharmacokinetics in other paediatric patients 
(paediatric psoriasis, juvenile idiopathic arthritis, paediatric Crohn’s disease, and enthesitis-related 
arthritis). No clinical exposure data are available on the use of a loading dose in children < 6 years. The 
predicted exposures indicate that in the absence of methotrexate, a loading dose may lead to an initial 
increase in systemic exposure. 
 
Population pharmacokinetic and pharmacokinetic/pharmacodynamic modelling and simulation predicted 
comparable adalimumab exposure and efficacy in patients treated with 80 mg every other week when 
compared with 40 mg every week (including adult patients with RA, HS, UC, CD or Ps, patients with 
adolescent HS, and paediatric patients ≥ 40 kg with CD and UC). 
 



151 

Exposure-response relationship in paediatric population 
 
On the basis of clinical trial data in patients with JIA (pJIA and ERA), an exposure-response relationship 
was established between plasma concentrations and PedACR 50 response. The apparent adalimumab 
plasma concentration that produces half the maximum probability of PedACR 50 response (EC50) was 
3 μg/ml (95% CI: 1-6 μg/ml).  
 
Exposure-response relationships between adalimumab concentration and efficacy in paediatric patients 
with severe chronic plaque psoriasis were established for PASI 75 and PGA clear or minimal, 
respectively. PASI 75 and PGA clear or minimal increased with increasing adalimumab concentrations, 
both with a similar apparent EC50 of approximately 4.5 μg/ml (95% CI 0.4-47.6 and 1.9-10.5, 
respectively).   
 
Elimination 
 
Population pharmacokinetic analyses with data from over 1,300 RA patients revealed a trend toward 
higher apparent clearance of adalimumab with increasing body weight. After adjustment for weight 
differences, gender and age appeared to have a minimal effect on adalimumab clearance.  The serum 
levels of free adalimumab (not bound to anti-adalimumab antibodies, AAA) were observed to be lower in 
patients with measurable AAA.   
 
Hepatic or renal impairment 
 
Humira has not been studied in patients with hepatic or renal impairment. 
 
5.3 Preclinical safety data  
 
Non-clinical data reveal no special hazard for humans based on studies of single dose toxicity, repeated 
dose toxicity, and genotoxicity.   
 
An embryo-foetal developmental toxicity/perinatal developmental study has been performed in 
cynomolgus monkeys at 0, 30 and 100 mg/kg (9-17 monkeys/group) and has revealed no evidence of harm 
to the foetuses due to adalimumab. Neither carcinogenicity studies, nor a standard assessment of fertility 
and postnatal toxicity, were performed with adalimumab due to the lack of appropriate models for an 
antibody with limited cross-reactivity to rodent TNF and to the development of neutralising antibodies in 
rodents.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients  
 
Mannitol 
Citric acid monohydrate 
Sodium citrate 
Sodium dihydrogen phosphate dihydrate 
Disodium phosphate dihydrate 
Sodium chloride 
Polysorbate 80 
Sodium hydroxide 
Water for injections 
 
6.2 Incompatibilities  



152 

 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life  
 
2 years 
 
6.4 Special precautions for storage  
 
Store in a refrigerator (2C – 8C). Do not freeze. Keep the pre-filled syringe or pre-filled pen in its outer 
carton in order to protect from light.   
 
A single Humira pre-filled syringe or pre-filled pen may be stored at temperatures up to a maximum of 
25°C for a period of up to 14 days. The syringe or pen must be protected from light, and discarded if not 
used within the 14-day period. 
 
6.5 Nature and contents of container   
 
Humira 40 mg solution for injection in pre-filled syringe  
Humira 40 mg solution for injection in single-use pre-filled syringe (type I glass) with a plunger stopper 
(bromobutyl rubber) and a needle with a needle shield (thermoplastic elastomer). 
 
Packs of: 
 1 pre-filled syringe (0.8 ml sterile solution) with 1 alcohol pad in a blister.  
 2 pre-filled syringes (0.8 ml sterile solution), each with 1 alcohol pad, in a blister.  
 4 pre-filled syringes (0.8 ml sterile solution), each with 1 alcohol pad, in a blister.  
 6 pre-filled syringes (0.8 ml sterile solution), each with 1 alcohol pad, in a blister. 
 
Humira 40 mg solution for injection in pre-filled syringe with needle guard  
Humira 40 mg solution for injection in single-use pre-filled syringe (type I glass) with needle guard for 
hospital and caregiver use. The syringe is made from type 1 glass with a plunger stopper (bromobutyl 
rubber) and a needle with a needle shield (thermoplastic elastomer). 
 
Packs of: 
1 pre-filled syringe with needle guard (0.8 ml sterile solution) in a blister, and 1 alcohol pad. 
 
Humira 40 mg solution for injection in pre-filled pen 
Humira 40 mg solution for injection in single-use pre-filled pen for patient use containing a pre-filled 
syringe. The syringe inside the pen is made from type 1 glass with a plunger stopper (bromobutyl rubber) 
and a needle with a needle shield (thermoplastic elastomer). 
 
Packs of: 

 1 pre-filled pen (0.8 ml sterile solution), with 2 alcohol pads in a blister.  
 2 pre-filled pens (0.8 ml sterile solution), each with 1 alcohol pad, in a blister.  
 4 pre-filled pens (0.8 ml sterile solution), each with 1 alcohol pad, in a blister.  
 6 pre-filled pens (0.8 ml sterile solution), each with 1 alcohol pad, in a blister. 

 
Not all presentations or pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 



153 

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER  
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
8. MARKETING AUTHORISATION NUMBERS  
 
Humira 40 mg solution for injection in pre-filled syringe  
EU/1/03/256/002 
EU/1/03/256/003 
EU/1/03/256/004 
EU/1/03/256/005 
 
Humira 40 mg solution for injection in pre-filled syringe with needle guard  
EU/1/03/256/006 
 
Humira 40 mg solution for injection in pre-filled pen 
EU/1/03/256/007 
EU/1/03/256/008 
EU/1/03/256/009 
EU/1/03/256/010 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation:  08 September 2003 
Date of latest renewal: 08 September 2008  
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 
  



154 

1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 40 mg solution for injection in pre-filled syringe 
Humira 40 mg solution for injection in pre-filled pen 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Humira 40 mg solution for injection in pre-filled syringe  
Each 0.4 ml single dose pre-filled syringe contains 40 mg of adalimumab. 
 
Humira 40 mg solution for injection in pre-filled syringe with automatic needle guard 
Each 0.4 ml single dose pre-filled syringe contains 40 mg of adalimumab. 
 
Humira 40 mg solution for injection in pre-filled pen 
Each 0.4 ml single dose pre-filled pen contains 40 mg of adalimumab. 
 
Adalimumab is a recombinant human monoclonal antibody produced in Chinese Hamster Ovary cells. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM  
 
Solution for injection. (injection) 
 
Clear, colourless solution.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications  
 
Rheumatoid arthritis 
 
Humira in combination with methotrexate, is indicated for: 
 
 the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the response 

to disease-modifying anti-rheumatic drugs including methotrexate has been inadequate. 
 the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated 

with methotrexate. 
 
Humira can be given as monotherapy in case of intolerance to methotrexate or when continued treatment 
with methotrexate is inappropriate. 
 
Humira has been shown to reduce the rate of progression of joint damage as measured by X-ray and to 
improve physical function, when given in combination with methotrexate. 
 



155 

Juvenile idiopathic arthritis 
 
Polyarticular juvenile idiopathic arthritis 
 
Humira in combination with methotrexate is indicated for the treatment of active polyarticular juvenile 
idiopathic arthritis, in patients from the age of 2 years who have had an inadequate response to one or 
more disease-modifying anti-rheumatic drugs (DMARDs). Humira can be given as monotherapy in case 
of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate (for the 
efficacy in monotherapy see section 5.1). Humira has not been studied in patients aged less than 2 years. 
 
Enthesitis-related arthritis 
 
Humira is indicated for the treatment of active enthesitis-related arthritis in patients, 6 years of age and 
older, who have had an inadequate response to, or who are intolerant of, conventional therapy (see section 
5.1). 
 
Axial spondyloarthritis  
 
Ankylosing spondylitis (AS) 
 
Humira is indicated for the treatment of adults with severe active ankylosing spondylitis who have had an 
inadequate response to conventional therapy. 
 
Axial spondyloarthritis without radiographic evidence of AS 
 
Humira is indicated for the treatment of adults with severe axial spondyloarthritis without radiographic 
evidence of AS but with objective signs of inflammation by elevated CRP and / or MRI, who have had an 
inadequate response to, or are intolerant to non-steroidal anti-inflammatory drugs (NSAIDs). 
 
Psoriatic arthritis 
 
Humira is indicated for the treatment of active and progressive psoriatic arthritis in adults when the 
response to previous disease-modifying anti-rheumatic drug therapy has been inadequate. Humira has 
been shown to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients 
with polyarticular symmetrical subtypes of the disease (see Section 5.1) and to improve physical function. 
 
Psoriasis 
 
Humira is indicated for the treatment of moderate to severe chronic plaque psoriasis in adult patients who 
are candidates for systemic therapy. 
 
Paediatric plaque psoriasis 
 
Humira is indicated for the treatment of severe chronic plaque psoriasis in children and adolescents from 
4 years of age who have had an inadequate response to or are inappropriate candidates for topical therapy 
and phototherapies. 
 
Hidradenitis suppurativa (HS) 
 
Humira is indicated for the treatment of active moderate to severe hidradenitis suppurativa (acne inversa) 
in adults and adolescents from 12 years of age with an inadequate response to conventional systemic HS 
therapy (see sections 5.1 and 5.2). 
 



156 

Crohn’s disease 
 
Humira is indicated for treatment of moderately to severely active Crohn’s disease, in adult patients who 
have not responded despite a full and adequate course of therapy with a corticosteroid and/or an 
immunosuppressant; or who are intolerant to or have medical contraindications for such therapies.  
 
Paediatric Crohn's disease  
 
Humira is indicated for the treatment of moderately to severely active Crohn's disease in paediatric 
patients (from 6 years of age) who have had an inadequate response to conventional therapy including 
primary nutrition therapy and a corticosteroid and/or an immunomodulator, or who are intolerant to or 
have contraindications for such therapies. 
 
Ulcerative colitis 
 
Humira is indicated for treatment of moderately to severely active ulcerative colitis in adult patients who 
have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine 
(6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such 
therapies.  
 
Paediatric ulcerative colitis 
 
Humira is indicated for the treatment of moderately to severely active ulcerative colitis in paediatric 
patients (from 6 years of age) who have had an inadequate response to conventional therapy including 
corticosteroids and/or 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have 
medical contraindications for such therapies. 
 
Uveitis 
 
Humira is indicated for the treatment of non-infectious intermediate, posterior and panuveitis in adult 
patients who have had an inadequate response to corticosteroids, in patients in need of corticosteroid-
sparing, or in whom corticosteroid treatment is inappropriate. 
 
Paediatric Uveitis 
 
Humira is indicated for the treatment of paediatric chronic non-infectious anterior uveitis in patients from 
2 years of age who have had an inadequate response to or are intolerant to conventional therapy, or in 
whom conventional therapy is inappropriate. 
 
4.2 Posology and method of administration   
 
Humira treatment should be initiated and supervised by specialist physicians experienced in the diagnosis 
and treatment of conditions for which Humira is indicated. Ophthalmologists are advised to consult with 
an appropriate specialist before initiation of treatment with Humira (see section 4.4). Patients treated with 
Humira should be given the Patient Reminder Card. 
 
After proper training in injection technique, patients may self-inject with Humira if their physician 
determines that it is appropriate and with medical follow-up as necessary.  
 
During treatment with Humira, other concomitant therapies (e.g., corticosteroids and/or 
immunomodulatory agents) should be optimised. 
 
Posology 



157 

 
Rheumatoid arthritis 
 
The recommended dose of Humira for adult patients with rheumatoid arthritis is 40 mg adalimumab 
administered every other week as a single dose via subcutaneous injection. Methotrexate should be 
continued during treatment with Humira. 
 
Glucocorticoids, salicylates, non-steroidal anti-inflammatory drugs, or analgesics can be continued during 
treatment with Humira.  Regarding combination with disease modifying anti-rheumatic drugs other than 
methotrexate see sections 4.4 and 5.1. 
 
In monotherapy, some patients who experience a decrease in their response to Humira 40 mg every other 
week may benefit from an increase in dosage to 40 mg adalimumab every week or 80 mg every other 
week.  
 
Available data suggest that the clinical response is usually achieved within 12 weeks of treatment.  
Continued therapy should be reconsidered in a patient not responding within this time period. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Dose interruption 
 
There may be a need for dose interruption, for instance before surgery or if a serious infection occurs. 
 
Available data suggest that re-introduction of Humira after discontinuation for 70 days or longer resulted 
in the same magnitudes of clinical response and similar safety profile as before dose interruption. 
 
Ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of AS and psoriatic arthritis 
 
The recommended dose of Humira for patients with ankylosing spondylitis, axial spondyloarthritis without 
radiographic evidence of AS and for patients with psoriatic arthritis is 40 mg adalimumab administered 
every other week as a single dose via subcutaneous injection. 
 
Available data suggest that the clinical response is usually achieved within 12 weeks of treatment.  
Continued therapy should be reconsidered in a patient not responding within this time period. 
 
Psoriasis 
 
The recommended dose of Humira for adult patients is an initial dose of 80 mg administered 
subcutaneously, followed by 40 mg subcutaneously given every other week starting one week after the 
initial dose. 
 
Continued therapy beyond 16 weeks should be carefully reconsidered in a patient not responding within 
this time period. 
 
Beyond 16 weeks, patients with inadequate response to Humira 40 mg every other week may benefit from 
an increase in dosage to 40 mg every week or 80 mg every other week. The benefits and risks of continued 
40 mg weekly or 80 mg every other week therapy should be carefully reconsidered in a patient with an 
inadequate response after the increase in dosage (see section 5.1).  If adequate response is achieved with 
40 mg every week or 80 mg every other week, the dosage may subsequently be reduced to 40 mg every 
other week. 
 



158 

Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Hidradenitis suppurativa 
 
The recommended Humira dose regimen for adult patients with hidradenitis suppurativa (HS) is 160 mg 
initially at Day 1 (given as four 40 mg injections in one day or as two 40 mg injections per day for two 
consecutive days), followed by 80 mg two weeks later at Day 15 (given as two 40 mg injections in one 
day). Two weeks later (Day 29) continue with a dose of 40 mg every week or 80 mg every other week 
(given as two 40 mg injections in one day). Antibiotics may be continued during treatment with Humira if 
necessary. It is recommended that the patient should use a topical antiseptic wash on their HS lesions on a 
daily basis during treatment with Humira. 
 
Continued therapy beyond 12 weeks should be carefully reconsidered in a patient with no improvement 
within this time period.   
 
Should treatment be interrupted, Humira 40 mg every week or 80 mg every other week may be re-
introduced (see section 5.1).  
 
The benefit and risk of continued long-term treatment should be periodically evaluated (see section 5.1). 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Crohn’s disease 
 
The recommended Humira induction dose regimen for adult patients with moderately to severely active 
Crohn’s disease is 80 mg at Week 0 followed by 40 mg at Week 2. In case there is a need for a more rapid 
response to therapy, the regimen 160 mg at Week 0 (given as four 40 mg injections in one day or as two 
40 mg injections per day for two consecutive days), followed by 80 mg at Week 2 (given as two 40 mg 
injections in one day), can be used with the awareness that the risk for adverse events is higher during 
induction. 
 
After induction treatment, the recommended dose is 40 mg every other week via subcutaneous injection. 
Alternatively, if a patient has stopped Humira and signs and symptoms of disease recur, Humira may be 
re-administered. There is little experience from re-administration after more than 8 weeks since the 
previous dose. 
 
During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice 
guidelines. 
 
Some patients who experience decrease in their response to Humira 40 mg every other week may benefit 
from an increase in dosage to 40 mg Humira every week or 80 mg every other week. 
 
Some patients who have not responded by Week 4 may benefit from continued maintenance therapy 
through Week 12. Continued therapy should be carefully reconsidered in a patient not responding within 
this time period. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Ulcerative colitis 
 



159 

The recommended Humira induction dose regimen for adult patients with moderate to severe ulcerative 
colitis is 160 mg at Week 0 (given as four 40 mg injections in one day or as two 40 mg injections per day 
for two consecutive days) and 80 mg at Week 2 (given as two 40 mg injections in one day). After 
induction treatment, the recommended dose is 40 mg every other week via subcutaneous injection.  
 
During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice 
guidelines.  
 
Some patients who experience decrease in their response to 40 mg every other week may benefit from an 
increase in dosage to 40 mg Humira every week or 80 mg every other week. 
 
Available data suggest that clinical response is usually achieved within 2-8 weeks of treatment.  Humira 
therapy should not be continued in patients failing to respond within this time period. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Uveitis 
 
The recommended dose of Humira for adult patients with uveitis is an initial dose of 80 mg, followed by 
40 mg given every other week starting one week after the initial dose. There is limited experience in the 
initiation of treatment with Humira alone. Treatment with Humira can be initiated in combination with 
corticosteroids and/or with other non-biologic immunomodulatory agents. Concomitant corticosteroids 
may be tapered in accordance with clinical practice starting two weeks after initiating treatment with 
Humira.    
 
It is recommended that the benefit and risk of continued long-term treatment should be evaluated on a 
yearly basis (see section 5.1).   
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Special populations  
 
Elderly 
 
No dose adjustment is required. 
 
Renal and/or hepatic impairment 
 
Humira has not been studied in these patient populations. No dose recommendations can be made. 
 
Paediatric population 
 
Juvenile idiopathic arthritis 
 
Polyarticular juvenile idiopathic arthritis from 2 years of age 
 
The recommended dose of Humira for patients with polyarticular juvenile idiopathic arthritis from 2 years 
of age is based on body weight (Table 1). Humira is administered every other week via subcutaneous 
injection. 
 

Table 1. Humira Dose for Patients with Polyarticular Juvenile Idiopathic Arthritis  



160 

 
Patient Weight Dosing Regimen 

10 kg to < 30 kg 20 mg every other week 

≥ 30 kg 40 mg every other week 
 
Available data suggest that clinical response is usually achieved within 12 weeks of treatment. Continued 
therapy should be carefully reconsidered in a patient not responding within this time period. 
 
There is no relevant use of Humira in patients aged less than 2 years for this indication. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Enthesitis-related arthritis 
 
The recommended dose of Humira for patients with enthesitis-related arthritis from 6 years of age is based 
on body weight (Table 2).  Humira is administered every other week via subcutaneous injection. 
 

Table 2. Humira Dose for Patients with Enthesitis-Related Arthritis  
 

Patient Weight Dosing Regimen 

15 kg to < 30 kg 20 mg every other week 

≥ 30 kg 40 mg every other week 
 
Humira has not been studied in patients with enthesitis-related arthritis aged less than 6 years. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Psoriatic arthritis and axial spondyloarthritis including ankylosing spondylitis 
 
There is no relevant use of Humira in the paediatric population for the indications of ankylosing 
spondylitis and psoriatic arthritis. 
 
Paediatric plaque psoriasis 
 
The recommended Humira dose for patients with plaque psoriasis from 4 to 17 years of age is based on 
body weight (Table 3). Humira is administered via subcutaneous injection.  
 



161 

Table 3. Humira Dose for Paediatric Patients with Plaque Psoriasis  
 

Patient Weight Dosing Regimen 

15 kg to < 30 kg Initial dose of 20 mg, followed by 
20 mg given every other week 

starting one week after the initial 
dose  

≥ 30 kg Initial dose of 40 mg, followed by 
40 mg given every other week 

starting one week after the initial 
dose 

 
Continued therapy beyond 16 weeks should be carefully considered in a patient not responding within this 
time period. 
 
If retreatment with Humira is indicated, the above guidance on dose and treatment duration should be 
followed. 
 
The safety of Humira in paediatric patients with plaque psoriasis has been assessed for a mean of 
13 months. 
 
There is no relevant use of Humira in children aged less than 4 years for this indication. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Adolescent hidradenitis suppurativa (from 12 years of age, weighing at least 30 kg) 
 
There are no clinical trials with Humira in adolescent patients with HS.  The posology of Humira in these 
patients has been determined from pharmacokinetic modelling and simulation (see section 5.2). 
 
The recommended Humira dose is 80 mg at Week 0 followed by 40 mg every other week starting at Week 
1 via subcutaneous injection.  
 
In adolescent patients with inadequate response to Humira 40 mg every other week, an increase in dosage 
to 40 mg every week or 80 mg every other week may be considered. 
 
Antibiotics may be continued during treatment with Humira if necessary.  It is recommended that the 
patient should use a topical antiseptic wash on their HS lesions on a daily basis during treatment with 
Humira.  
 
Continued therapy beyond 12 weeks should be carefully reconsidered in a patient with no improvement 
within this time period.   
 
Should treatment be interrupted, Humira may be re-introduced as appropriate. 
 
The benefit and risk of continued long-term treatment should be periodically evaluated (see adult data in 
section 5.1) 
 
There is no relevant use of Humira in children aged less than 12 years in this indication. 



162 

 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Paediatric Crohn's disease 
 
The recommended dose of Humira for patients with Crohn’s disease from 6 to 17 years of age is based on 
body weight (Table 4). Humira is administered via subcutaneous injection. 
 

Table 4. Humira Dose for Paediatric Patients with Crohn’s disease 
 

Patient 
Weight 

Induction Dose Maintenance 
Dose 

Starting at 
Week 4

< 40 kg  40 mg at week 0 and 20 mg at week 2 
 

In case there is a need for a more rapid response to therapy with the 
awareness that the risk for adverse events may be higher with use of the 
higher induction dose, the following dose may be used: 
 80 mg at week 0 and 40 mg at week 2

20 mg every 
other week 

≥ 40 kg  80 mg at week 0 and 40 mg at week 2 
 

In case there is a need for a more rapid response to therapy with the 
awareness that the risk for adverse events may be higher with use of the 
higher induction dose, the following dose may be used: 
 160 mg at week 0 and 80 mg at week 2

40 mg every 
other week 

 
Patients who experience insufficient response may benefit from an increase in dosage: 
 < 40 kg: 20 mg every week 
 ≥ 40 kg: 40 mg every week or 80 mg every other week 

 
Continued therapy should be carefully considered in a subject not responding by week 12. 
 
There is no relevant use of Humira in children aged less than 6 years for this indication. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Paediatric ulcerative colitis  
 
The recommended dose of Humira for patients from 6 to 17 years of age with ulcerative colitis is based on 
body weight (Table 5). Humira is administered via subcutaneous injection.  
 

Table 5. Humira Dose for Paediatric Patients with Ulcerative Colitis  

Patient Weight Induction Dose 
Maintenance Dose 

Starting at Week 4* 
< 40 kg • 80 mg at Week 0 (given as two 40 

mg injections in one day) and 
• 40 mg at Week 2 (given as one 40 

mg injection)

• 40 mg every other week 



163 

≥ 40 kg • 160 mg at Week 0 (given as four 
40 mg injections in one day or 
two 40 mg injections per day for 
two consecutive days) and 

• 80 mg at Week 2 (given as two 40 
mg injections in one day)

• 80 mg every other week 

* Paediatric patients who turn 18 years of age while on Humira should continue their prescribed 
maintenance dose. 

  

Continued therapy beyond 8 weeks should be carefully considered in patients not showing signs of 
response within this time period. 
 
There is no relevant use of Humira in children aged less than 6 years in this indication. 
 
Humira may be available in different strengths and/or presentations depending on the individual treatment 
needs. 
 
Paediatric Uveitis  
 
The recommended dose of Humira for paediatric patients with uveitis from 2 years of age is based on 
body weight (Table 6). Humira is administered via subcutaneous injection. 
 
In paediatric uveitis, there is no experience in the treatment with Humira without concomitant treatment 
with methotrexate. 
 

Table 6. Humira Dose for Paediatric Patients with Uveitis 
 

Patient Weight Dosing Regimen 

< 30 kg 20 mg every other week in 
combination with methotrexate 

≥ 30 kg 40 mg every other week in 
combination with methotrexate 

 
When Humira therapy is initiated, a loading dose of 40 mg for patients < 30 kg or 80 mg for patients 
≥ 30 kg may be administered one week prior to the start of maintenance therapy. No clinical data are 
available on the use of a Humira loading dose in children < 6 years of age (see section 5.2). 
 
There is no relevant use of Humira in children aged less than 2 years in this indication. 
 
It is recommended that the benefit and risk of continued long-term treatment should be evaluated on a 
yearly basis (see section 5.1). 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Method of administration 
 
Humira is administered by subcutaneous injection. Full instructions for use are provided in the package 
leaflet. 
 
Humira is available in other strengths and presentations. 
 



164 

4.3 Contraindications  
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  
 
Active tuberculosis or other severe infections such as sepsis, and opportunistic infections (see section 4.4). 
 
Moderate to severe heart failure (NYHA class III/IV) (see section 4.4). 
 
4.4 Special warnings and precautions for use 
 
Traceability  
 
In order to improve traceability of biological medicinal products, the name and the batch number of the 
administered product should be clearly recorded. 
 
Infections 
 
Patients taking TNF-antagonists are more susceptible to serious infections. Impaired lung function may 
increase the risk for developing infections. Patients must therefore be monitored closely for infections, 
including tuberculosis, before, during and after treatment with Humira.  Because the elimination of 
adalimumab may take up to four months, monitoring should be continued throughout this period. 
 
Treatment with Humira should not be initiated in patients with active infections including chronic or 
localised infections until infections are controlled. In patients who have been exposed to tuberculosis and 
patients who have travelled in areas of high risk of tuberculosis or endemic mycoses, such as 
histoplasmosis, coccidioidomycosis, or blastomycosis, the risk and benefits of treatment with Humira 
should be considered prior to initiating therapy (see Other opportunistic infections). 
 
Patients who develop a new infection while undergoing treatment with Humira should be monitored 
closely and undergo a complete diagnostic evaluation. Administration of Humira should be discontinued if 
a patient develops a new serious infection or sepsis, and appropriate antimicrobial or antifungal therapy 
should be initiated until the infection is controlled.  Physicians should exercise caution when considering 
the use of Humira in patients with a history of recurring infection or with underlying conditions which 
may predispose patients to infections, including the use of concomitant immunosuppressive medications. 
 
Serious infections 
 
Serious infections, including sepsis, due to bacterial, mycobacterial, invasive fungal, parasitic, viral, or 
other opportunistic infections such as listeriosis, legionellosis and pneumocystis have been reported in 
patients receiving Humira.   
 
Other serious infections seen in clinical trials include pneumonia, pyelonephritis, septic arthritis and 
septicaemia. Hospitalisation or fatal outcomes associated with infections have been reported.  
 
Tuberculosis 
 
Tuberculosis, including reactivation and new onset of tuberculosis, has been reported in patients receiving 
Humira.  Reports included cases of pulmonary and extra-pulmonary (i.e. disseminated) tuberculosis.  
 
Before initiation of therapy with Humira, all patients must be evaluated for both active or inactive 
(“latent”) tuberculosis infection.  This evaluation should include a detailed medical assessment of patient 
history of tuberculosis or possible previous exposure to people with active tuberculosis and previous 
and/or current immunosuppressive therapy.  Appropriate screening tests (i.e. tuberculin skin test and chest 



165 

X-ray) should be performed in all patients (local recommendations may apply).  It is recommended that 
the conduct and results of these tests are recorded in the Patient Reminder Card.  Prescribers are reminded 
of the risk of false negative tuberculin skin test results, especially in patients who are severely ill or 
immunocompromised.  
 
If active tuberculosis is diagnosed, Humira therapy must not be initiated (see section 4.3).  
 
In all situations described below, the benefit/risk balance of therapy should be very carefully considered. 
 
If latent tuberculosis is suspected, a physician with expertise in the treatment of tuberculosis should be 
consulted.   
 
If latent tuberculosis is diagnosed, appropriate treatment must be started with anti-tuberculosis prophylaxis 
treatment before the initiation of Humira, and in accordance with local recommendations.  
 
Use of anti-tuberculosis prophylaxis treatment should also be considered before the initiation of Humira in 
patients with several or significant risk factors for tuberculosis despite a negative test for tuberculosis and 
in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment 
cannot be confirmed.   
 
Despite prophylactic treatment for tuberculosis, cases of reactivated tuberculosis have occurred in patients 
treated with Humira. Some patients who have been successfully treated for active tuberculosis have 
redeveloped tuberculosis while being treated with Humira. 
 
Patients should be instructed to seek medical advice if signs/symptoms suggestive of a tuberculosis 
infection (e.g., persistent cough, wasting/weight loss, low grade fever, listlessness) occur during or after 
therapy with Humira.  
 
Other opportunistic infections 
 
Opportunistic infections, including invasive fungal infections have been observed in patients receiving 
Humira. These infections have not consistently been recognised in patients taking TNF-antagonists and 
this has resulted in delays in appropriate treatment, sometimes resulting in fatal outcomes.  
 
For patients who develop the signs and symptoms such as fever, malaise, weight loss, sweats, cough, 
dyspnoea, and/or pulmonary infiltrates or other serious systemic illness with or without concomitant shock 
an invasive fungal infection should be suspected and administration of Humira should be promptly 
discontinued.  Diagnosis and administration of empiric antifungal therapy in these patients should be made 
in consultation with a physician with expertise in the care of patients with invasive fungal infections.  
 
Hepatitis B reactivation 
 
Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including Humira, who are 
chronic carriers of this virus (i.e. surface antigen positive).  Some cases have had a fatal outcome. Patients 
should be tested for HBV infection before initiating treatment with Humira. For patients who test positive 
for hepatitis B infection, consultation with a physician with expertise in the treatment of hepatitis B is 
recommended. 
 
Carriers of HBV who require treatment with Humira should be closely monitored for signs and symptoms 
of active HBV infection throughout therapy and for several months following termination of therapy. 
Adequate data from treating patients who are carriers of HBV with anti-viral therapy in conjunction with 
TNF-antagonist therapy to prevent HBV reactivation are not available. In patients who develop HBV 



166 

reactivation, Humira should be stopped and effective anti-viral therapy with appropriate supportive 
treatment should be initiated.  
 
Neurological events  
 
TNF-antagonists including Humira have been associated in rare instances with new onset or exacerbation 
of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease 
including multiple sclerosis and optic neuritis, and peripheral demyelinating disease, including Guillain-
Barré syndrome. Prescribers should exercise caution in considering the use of Humira in patients with pre-
existing or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of 
Humira should be considered if any of these disorders develop. There is a known association between 
intermediate uveitis and central demyelinating disorders. Neurologic evaluation should be performed in 
patients with non-infectious intermediate uveitis prior to the initiation of Humira therapy and regularly 
during treatment to assess for pre-existing or developing central demyelinating disorders.  
 
Allergic reactions 
 
Serious allergic reactions associated with Humira were rare during clinical trials. Non-serious allergic 
reactions associated with Humira were uncommon during clinical trials. Reports of serious allergic 
reactions including anaphylaxis have been received following Humira administration. If an anaphylactic 
reaction or other serious allergic reaction occurs, administration of Humira should be discontinued 
immediately and appropriate therapy initiated.  
 
Immunosuppression 
 
In a study of 64 patients with rheumatoid arthritis that were treated with Humira, there was no evidence of 
depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or change in 
enumeration of effector T-, B-, NK-cells, monocyte/macrophages, and neutrophils. 
 
Malignancies and lymphoproliferative disorders 
 
In the controlled portions of clinical trials of TNF-antagonists, more cases of malignancies including 
lymphoma have been observed among patients receiving a TNF-antagonist compared with control 
patients. However, the occurrence was rare. In the post marketing setting, cases of leukaemia have been 
reported in patients treated with a TNF-antagonist. There is an increased background risk for lymphoma 
and leukaemia in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, 
which complicates the risk estimation. With the current knowledge, a possible risk for the development of 
lymphomas, leukaemia, and other malignancies in patients treated with a TNF-antagonist cannot be 
excluded. 
 
Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 
22 years of age) treated with TNF-antagonists (initiation of therapy ≤ 18 years of age), including 
adalimumab in the post marketing setting. Approximately half the cases were lymphomas. The other cases 
represented a variety of different malignancies and included rare malignancies usually associated with 
immunosuppression. A risk for the development of malignancies in children and adolescents treated with 
TNF-antagonists cannot be excluded.  
 
Rare postmarketing cases of hepatosplenic T-cell lymphoma have been identified in patients treated with 
adalimumab. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. 
Some of these hepatosplenic T-cell lymphomas with Humira have occurred in young adult patients on 
concomitant treatment with azathioprine or 6-mercaptopurine used for inflammatory bowel disease. The 
potential risk with the combination of azathioprine or 6-mercaptopurine and Humira should be carefully 



167 

considered. A risk for the development of hepatosplenic T-cell lymphoma in patients treated with Humira 
cannot be excluded (see section 4.8). 
 
No studies have been conducted that include patients with a history of malignancy or in whom treatment 
with Humira is continued following development of malignancy.  Thus, additional caution should be 
exercised in considering Humira treatment of these patients (see section 4.8). 
 
All patients, and in particular patients with a medical history of extensive immunosuppressant therapy or 
psoriasis patients with a history of PUVA treatment should be examined for the presence of non-
melanoma skin cancer prior to and during treatment with Humira.  Melanoma and Merkel cell carcinoma 
have also been reported in patients treated with TNF-antagonists including adalimumab (see section 4.8). 
 
In an exploratory clinical trial evaluating the use of another TNF-antagonist, infliximab, in patients with 
moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, mostly in the lung 
or head and neck, were reported in infliximab-treated patients compared with control patients. All patients 
had a history of heavy smoking. Therefore, caution should be exercised when using any TNF-antagonist in 
COPD patients, as well as in patients with increased risk for malignancy due to heavy smoking. 
 
With current data it is not known if adalimumab treatment influences the risk for developing dysplasia or 
colon cancer.  All patients with ulcerative colitis who are at increased risk for dysplasia or colon 
carcinoma (for example, patients with long-standing ulcerative colitis or primary sclerosing cholangitis), 
or who had a prior history of dysplasia or colon carcinoma should be screened for dysplasia at regular 
intervals before therapy and throughout their disease course. This evaluation should include colonoscopy 
and biopsies per local recommendations. 
 
Haematologic reactions 
 
Rare reports of pancytopenia including aplastic anaemia have been reported with TNF-antagonists.  
Adverse events of the haematologic system, including medically significant cytopenia (e.g. 
thrombocytopenia, leukopenia) have been reported with Humira. All patients should be advised to seek 
immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias (e.g. 
persistent fever, bruising, bleeding, pallor) while on Humira. Discontinuation of Humira therapy should be 
considered in patients with confirmed significant haematologic abnormalities. 
 
Vaccinations  
 
Similar antibody responses to the standard 23-valent pneumococcal vaccine and the influenza trivalent 
virus vaccination were observed in a study in 226 adult subjects with rheumatoid arthritis who were 
treated with adalimumab or placebo. No data are available on the secondary transmission of infection by 
live vaccines in patients receiving Humira.   
 
It is recommended that paediatric patients, if possible, be brought up to date with all immunisations in 
agreement with current immunisation guidelines prior to initiating Humira therapy. 
 
Patients on Humira may receive concurrent vaccinations, except for live vaccines. Administration of live 
vaccines (e.g., BCG vaccine) to infants exposed to adalimumab in utero is not recommended for 5 months 
following the mother’s last adalimumab injection during pregnancy. 
 
Congestive heart failure 
 
In a clinical trial with another TNF-antagonist worsening congestive heart failure and increased mortality 
due to congestive heart failure have been observed. Cases of worsening congestive heart failure have also 
been reported in patients receiving Humira. Humira should be used with caution in patients with mild 



168 

heart failure (NYHA class I/II). Humira is contraindicated in moderate to severe heart failure (see section 
4.3). Treatment with Humira must be discontinued in patients who develop new or worsening symptoms 
of congestive heart failure. 
 
Autoimmune processes 
 
Treatment with Humira may result in the formation of autoimmune antibodies. The impact of long-term 
treatment with Humira on the development of autoimmune diseases is unknown. If a patient develops 
symptoms suggestive of a lupus-like syndrome following treatment with Humira and is positive for 
antibodies against double-stranded DNA, further treatment with Humira should not be given (see section 
4.8). 
 
Concurrent administration of biologic DMARDS or TNF-antagonists 
 
Serious infections were seen in clinical studies with concurrent use of anakinra and another 
TNF-antagonist, etanercept, with no added clinical benefit compared to etanercept alone. Because of the 
nature of the adverse events seen with the combination of etanercept and anakinra therapy, similar 
toxicities may also result from the combination of anakinra and other TNF-antagonists. Therefore, the 
combination of adalimumab and anakinra is not recommended. (See section 4.5). 
 
Concomitant administration of adalimumab with other biologic DMARDS (e.g, anakinra and abatacept) or 
other TNF-antagonists is not recommended based upon the possible increased risk for infections, 
including serious infections and other potential pharmacological interactions. (See section 4.5). 
 
Surgery 
 
There is limited safety experience of surgical procedures in patients treated with Humira. The long half-
life of adalimumab should be taken into consideration if a surgical procedure is planned.  A patient who 
requires surgery while on Humira should be closely monitored for infections, and appropriate actions 
should be taken. There is limited safety experience in patients undergoing arthroplasty while receiving 
Humira.  
 
Small bowel obstruction 
 
Failure to respond to treatment for Crohn’s disease may indicate the presence of fixed fibrotic stricture 
that may require surgical treatment. Available data suggest that Humira does not worsen or cause 
strictures. 
 
Elderly 
 
The frequency of serious infections among Humira treated subjects over 65 years of age (3.7%) was 
higher than for those under 65 years of age (1.5%). Some of those had a fatal outcome. Particular attention 
regarding the risk for infection should be paid when treating the elderly. 
 
Paediatric population 
 
See Vaccinations above. 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
Humira has been studied in rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and psoriatic 
arthritis patients taking Humira as monotherapy and those taking concomitant methotrexate.  Antibody 
formation was lower when Humira was given together with methotrexate in comparison with use as 



169 

monotherapy. Administration of Humira without methotrexate resulted in increased formation of 
antibodies, increased clearance and reduced efficacy of adalimumab (see section 5.1).  
 
The combination of Humira and anakinra is not recommended (see section 4.4 “Concurrent administration 
of biologic DMARDS or TNF-antagonists”).  
 
The combination of Humira and abatacept is not recommended (see section 4.4 “Concurrent 
administration of biologic DMARDS or TNF-antagonists”). 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential 
 
Women of childbearing potential should consider the use of adequate contraception to prevent pregnancy 
and continue its use for at least five months after the last Humira treatment. 
 
Pregnancy 
 
A large number (approximately 2100) of prospectively collected pregnancies exposed to adalimumab 
resulting in live birth with known outcomes, including more than 1500 exposed during the first trimester, 
does not indicate an increase in the rate of malformation in the newborn. 
 
In a prospective cohort registry, 257 women with rheumatoid arthritis (RA) or Crohn’s disease (CD) 
treated with adalimumab at least during the first trimester and 120 women with RA or CD not treated with 
adalimumab were enrolled.  The primary endpoint was the birth prevalence of major birth defects. The 
rate of pregnancies ending with at least one live born infant with a major birth defect was 6/69 (8.7%) in 
the adalimumab-treated women with RA and 5/74 (6.8%) in the untreated women with RA (unadjusted 
OR 1.31, 95% CI 0.38-4.52) and 16/152 (10.5%) in the adalimumab-treated women with CD and 3/32 
(9.4%) in the untreated women with CD (unadjusted OR 1.14, 95% CI 0.31-4.16). The adjusted OR 
(accounting for baseline differences) was 1.10 (95% CI 0.45-2.73) with RA and CD combined. There were 
no distinct differences between adalimumab-treated and untreated women for the secondary endpoints 
spontaneous abortions, minor birth defects, preterm delivery, birth size and serious or opportunistic 
infections and no stillbirths or malignancies were reported. The interpretation of data may be impacted due 
to methodological limitations of the study, including small sample size and non-randomized design. 
 
In a developmental toxicity study conducted in monkeys, there was no indication of maternal toxicity, 
embryotoxicity or teratogenicity. Preclinical data on postnatal toxicity of adalimumab are not available 
(see section 5.3). 
 
Due to its inhibition of TNF, adalimumab administered during pregnancy could affect normal immune 
responses in the newborn. Adalimumab should only be used during pregnancy if clearly needed.   
 
Adalimumab may cross the placenta into the serum of infants born to women treated with adalimumab 
during pregnancy. Consequently, these infants may be at increased risk for infection. Administration of 
live vaccines (e.g., BCG vaccine) to infants exposed to adalimumab in utero is not recommended for 
5 months following the mother’s last adalimumab injection during pregnancy. 
 
Breast-feeding 
 
Limited information from the published literature indicates that adalimumab is excreted in breast milk at 
very low concentrations with the presence of adalimumab in human milk at concentrations of 0.1% to 1% 
of the maternal serum level. Given orally, immunoglobulin G proteins undergo intestinal proteolysis and 



170 

have poor bioavailability. No effects on the breastfed newborns/infants are anticipated. Consequently, 
Humira can be used during breastfeeding. 
 
Fertility 
 
Preclinical data on fertility effects of adalimumab are not available. 
 
4.7 Effects on ability to drive and use machines  
 
Humira may have a minor influence on the ability to drive and use machines. Vertigo and visual 
impairment may occur following administration of Humira (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Humira was studied in 9,506 patients in pivotal controlled and open label trials for up to 60 months or 
more.  These trials included rheumatoid arthritis patients with short term and long standing disease, 
juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis) as 
well as axial spondyloarthritis (ankylosing spondylitis and axial spondyloarthritis without radiographic 
evidence of AS), psoriatic arthritis, Crohn’s disease, ulcerative colitis, psoriasis, hidradenitis suppurativa 
and uveitis patients. The pivotal controlled studies involved 6,089 patients receiving Humira and 3,801 
patients receiving placebo or active comparator during the controlled period. 
 
The proportion of patients who discontinued treatment due to adverse events during the double-blind, 
controlled portion of pivotal studies was 5.9% for patients taking Humira and 5.4% for control treated 
patients. 
 
The most commonly reported adverse reactions are infections (such as nasopharyngitis, upper respiratory 
tract infection and sinusitis), injection site reactions (erythema, itching, haemorrhage, pain or swelling), 
headache and musculoskeletal pain. 
 
Serious adverse reactions have been reported for Humira. TNF-antagonists, such as Humira affect the 
immune system and their use may affect the body’s defence against infection and cancer. 
Fatal and life-threatening infections (including sepsis, opportunistic infections and TB), HBV reactivation 
and various malignancies (including leukaemia, lymphoma and HSTCL) have also been reported with use 
of Humira. 
 
Serious haematological, neurological and autoimmune reactions have also been reported. These include 
rare reports of pancytopenia, aplastic anaemia, central and peripheral demyelinating events and reports of 
lupus, lupus-related conditions and Stevens-Johnson syndrome. 
 
Paediatric population 
 
In general, the adverse events in paediatric patients were similar in frequency and type to those seen in 
adult patients. 
 
Tabulated list of adverse reactions 
 
The following list of adverse reactions is based on experience from clinical trials and on postmarketing 
experience and are displayed by system organ class and frequency in Table 7 below: very common 
( 1/10); common ( 1/100 to < 1/10); uncommon ( 1/1,000 to < 1/100); rare ( 1/10,000 to < 1/1,000); 
and not known (cannot be estimated from the available data). Within each frequency grouping, 



171 

undesirable effects are presented in order of decreasing seriousness. The highest frequency seen among the 
various indications has been included. An asterisk (*) appears in the SOC column if further information is 
found elsewhere in sections 4.3, 4.4 and 4.8. 
 

Table 7 
Undesirable Effects 

 

System Organ Class Frequency Adverse Reaction 

Infections and 
infestations* 

 

Very common Respiratory tract infections (including lower and 
upper respiratory tract infection, pneumonia, 
sinusitis, pharyngitis, nasopharyngitis and 
pneumonia herpes viral) 

Common 

 

Systemic infections (including sepsis, candidiasis 
and influenza), 
intestinal infections (including gastroenteritis 
viral), 
skin and soft tissue infections (including 
paronychia, cellulitis, impetigo, necrotising 
fasciitis and herpes zoster), 
ear infections, 
oral infections (including herpes simplex, oral 
herpes and tooth infections),  
reproductive tract infections (including 
vulvovaginal mycotic infection),  

urinary tract infections (including 
pyelonephritis), 

fungal infections, 

joint infections 

Uncommon 
 

Neurological infections (including viral 
meningitis), 
opportunistic infections and tuberculosis 
(including coccidioidomycosis, histoplasmosis 
and mycobacterium avium complex infection),  
bacterial infections, 
eye infections, 
diverticulitis1)  

Neoplasms benign, 
malignant and unspecified 
(including cysts and 
polyps)* 

Common 

 

Skin cancer excluding melanoma (including 
basal cell carcinoma and squamous cell 
carcinoma), 

benign neoplasm 

Uncommon 
 

Lymphoma**,  
solid organ neoplasm (including breast cancer, 
lung neoplasm and thyroid neoplasm),  
melanoma** 



172 

System Organ Class Frequency Adverse Reaction 

 Rare Leukaemia1) 

Not known Hepatosplenic T-cell lymphoma1) 

Merkel cell carcinoma (neuroendocrine 
carcinoma of the skin)1), 

Kaposi’s sarcoma 

Blood and the lymphatic 
system disorders* 

Very common 

 

Leukopenia (including neutropenia and 
agranulocytosis),  

anaemia 

 
Common Leucocytosis, 

thrombocytopenia 

Uncommon Idiopathic thrombocytopenic purpura 

Rare 
 

Pancytopenia 

Immune system disorders* Common 

 

Hypersensitivity, 

allergies (including seasonal allergy) 

Uncommon Sarcoidosis1), 

vasculitis 

Rare Anaphylaxis1) 

Metabolism and nutrition 
disorders 

Very common 

 

Lipids increased 

Common Hypokalaemia,  

uric acid increased,  

blood sodium abnormal, 

hypocalcaemia, 

hyperglycaemia, 

hypophosphatemia, 

dehydration 

Psychiatric disorders Common 

 

Mood alterations (including depression),  

anxiety, 

insomnia 

Nervous system disorders* Very common 

 

Headache 



173 

System Organ Class Frequency Adverse Reaction 

Common 

 

Paraesthesias (including hypoesthesia), 

migraine, 

nerve root compression 

Uncommon 
 

Cerebrovascular accident1), 
tremor, 
neuropathy   

Rare 
 

Multiple sclerosis, 

demyelinating disorders (e.g. optic neuritis, 
Guillain-Barré syndrome) 1) 

Eye disorders Common 

 

Visual impairment, 

conjunctivitis, 

blepharitis, 

eye swelling 

Uncommon Diplopia 

Ear and labyrinth 
disorders  

 

Common 

 

Vertigo 

Uncommon 
 

Deafness,  
tinnitus 

Cardiac disorders*  Common Tachycardia 

Uncommon 

 

Myocardial infarction1), 

arrhythmia, 

congestive heart failure 

Rare 
 

Cardiac arrest 

Vascular disorders Common 

 

Hypertension,  

flushing,  

haematoma 

Uncommon Aortic aneurysm, 
vascular arterial occlusion, 
thrombophlebitis    

Respiratory, thoracic and 
mediastinal disorders* 

Common 

 

Asthma, 

dyspnoea, 

cough 



174 

System Organ Class Frequency Adverse Reaction 

Uncommon 
 

Pulmonary embolism1), 
interstitial lung disease,  
chronic obstructive pulmonary disease, 
pneumonitis, 
pleural effusion1) 

Rare Pulmonary fibrosis1)

Gastrointestinal disorders Very common 

 

Abdominal pain,  

nausea and vomiting 

Common 
 

GI haemorrhage,  
dyspepsia,  
gastroesophageal reflux disease, 
sicca syndrome 

Uncommon 
 

Pancreatitis,  
dysphagia, 
face oedema 

Rare Intestinal perforation1) 

Hepato-biliary disorders* Very Common 

 

Elevated liver enzymes 

Uncommon 
 

Cholecystitis and cholelithiasis, 
hepatic steatosis, 
bilirubin increased 

Rare 
 

Hepatitis 

reactivation of hepatitis B1)  

autoimmune hepatitis1) 

Not known 

 

Liver failure1) 

Skin and subcutaneous 
tissue disorders 

Very Common 

 

Rash (including exfoliative rash) 

Common 
 

Worsening or new onset of psoriasis(including 
palmoplantar pustular psoriasis)1), 
urticaria, 
bruising (including purpura),  
dermatitis (including eczema), 
onychoclasis,  
hyperhidrosis, 
alopecia1), 
pruritus  

Uncommon Night sweats,



175 

System Organ Class Frequency Adverse Reaction 

 scar 

Rare Erythema multiforme1), 

Stevens-Johnson syndrome1), 

angioedema1), 

cutaneous vasculitis1) 

lichenoid skin reaction1) 

Not known Worsening of symptoms of dermatomyositis1) 

Musculoskeletal and 
connective tissue disorders 

Very common 

 

Musculoskeletal pain 

Common Muscle spasms (including blood creatine 
phosphokinase increased) 

Uncommon Rhabdomyolysis, 
systemic lupus erythematosus 

Rare 
 

Lupus-like syndrome1)

Renal and urinary 
disorders  

Common 

 

Renal impairment, 

haematuria 

Uncommon 
 

Nocturia 

Reproductive system and 
breast disorders 

Uncommon Erectile dysfunction 

General disorders and 
administration site 
conditions* 

Very Common 

 

Injection site reaction (including injection site 
erythema) 

Common 
 

Chest pain,  
oedema, 
pyrexia1) 

Uncommon 
 

Inflammation 

Investigations* Common Coagulation and bleeding disorders (including 
activated partial thromboplastin time prolonged), 

autoantibody test positive (including double 
stranded DNA antibody),  

blood lactate dehydrogenase increased 

Injury, poisoning and 
procedural complications 

Common Impaired healing 

 



176 

* further information is found elsewhere in sections 4.3, 4.4 and 4.8 
** including open label extension studies 
1) including spontaneous reporting data 
 
Hidradenitis suppurativa 
 
The safety profile for patients with HS treated with Humira weekly was consistent with the known safety 
profile of Humira. 
 
Uveitis 
 
The safety profile for patients with uveitis treated with Humira every other week was consistent with the 
known safety profile of Humira. 
 
Description of selected adverse reactions 
 
Injection site reactions 
 
In the pivotal controlled trials in adults and children, 12.9% of patients treated with Humira developed 
injection site reactions (erythema and/or itching, haemorrhage, pain or swelling), compared to 7.2% of 
patients receiving placebo or active control. Injection site reactions generally did not necessitate 
discontinuation of the medicinal product. 
 
Infections  
 
In the pivotal controlled trials in adults and children, the rate of infection was 1.51 per patient year in the 
Humira treated patients and 1.46 per patient year in the placebo and active control-treated patients. The 
infections consisted primarily of nasopharyngitis, upper respiratory tract infection, and sinusitis. Most 
patients continued on Humira after the infection resolved.   
 
The incidence of serious infections was 0.04 per patient year in Humira treated patients and 0.03 per 
patient year in placebo and active control − treated patients.   
 
In controlled and open label adult and paediatric studies with Humira, serious infections (including fatal 
infections, which occurred rarely) have been reported, which include reports of tuberculosis (including 
miliary and extra-pulmonary locations) and invasive opportunistic infections (e.g. disseminated or 
extrapulmonary histoplasmosis, blastomycosis, coccidioidomycosis, pneumocystis, candidiasis, 
aspergillosis and listeriosis). Most of the cases of tuberculosis occurred within the first eight months after 
initiation of therapy and may reflect recrudescence of latent disease. 
 
Malignancies and lymphoproliferative disorders 
 
No malignancies were observed in 249 paediatric patients with an exposure of 655.6 patient years during 
Humira trials in patients with juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and 
enthesitis-related arthritis). In addition, no malignancies were observed in 192 paediatric patients with an 
exposure of 498.1 patient years during Humira trials in paediatric patients with Crohn’s disease. No 
malignancies were observed in 77 paediatric patients with an exposure of 80.0 patient years during a 
Humira trial in paediatric patients with chronic plaque psoriasis. No malignancies were observed in 93 
paediatric patients with an exposure of 65.3 patient years during a Humira trial in paediatric patients with 
ulcerative colitis. No malignancies were observed in 60 paediatric patients with an exposure of 58.4 
patient years during a Humira trial in paediatric patients with uveitis. 
 



177 

During the controlled portions of pivotal Humira trials in adults of at least 12 weeks in duration in patients 
with moderately to severely active rheumatoid arthritis, ankylosing spondylitis, axial spondyloarthritis 
without radiographic evidence of AS,  psoriatic arthritis, psoriasis, hidradenitis suppurativa, Crohn’s 
disease, ulcerative colitis and uveitis, malignancies, other than lymphoma and non-melanoma skin cancer, 
were observed at a rate (95% confidence interval) of 6.8 (4.4, 10.5)  per 1,000 patient-years among 5,291 
Humira treated patients versus a rate of 6.3 (3.4, 11.8) per 1,000 patient-years among 3,444 control 
patients (median duration of treatment was 4.0 months for Humira and 3.8 months for control-treated 
patients). The rate (95% confidence interval) of non-melanoma skin cancers was 8.8 (6.0, 13.0) per 1,000 
patient-years among Humira-treated patients and 3.2 (1.3, 7.6) per 1,000 patient-years among control 
patients. Of these skin cancers, squamous cell carcinomas occurred at rates (95% confidence interval) of 
2.7 (1.4, 5.4) per 1,000 patient-years among Humira-treated patients and 0.6 (0.1, 4.5) per 1,000 patient-
years among control patients. The rate (95% confidence interval) of lymphomas was 0.7 (0.2, 2.7) per 
1,000 patient-years among Humira-treated patients and 0.6 (0.1, 4.5) per 1,000 patient-years among 
control patients. 
 
When combining controlled portions of these trials and ongoing and completed open label extension 
studies with a median duration of approximately 3.3 years including 6,427 patients and over 26,439 
patient-years of therapy, the observed rate of malignancies, other than lymphoma and non-melanoma skin 
cancers is approximately 8.5 per 1,000 patient years. The observed rate of non-melanoma skin cancers is 
approximately 9.6 per 1,000 patient years, and the observed rate of lymphomas is approximately 1.3 per 
1,000 patient years. 
 
In post-marketing experience from January 2003 to December 2010, predominantly in patients with 
rheumatoid arthritis, the reported rate of malignancies is approximately 2.7 per 1,000 patient treatment 
years. The reported rates for non-melanoma skin cancers and lymphomas are approximately 0.2 and 0.3 
per 1,000 patient treatment years, respectively (see section 4.4). 
 
Rare post-marketing cases of hepatosplenic T-cell lymphoma have been reported in patients treated with 
adalimumab (see section 4.4). 
 
Autoantibodies  
 
Patients had serum samples tested for autoantibodies at multiple time points in rheumatoid arthritis studies 
I − V. In these trials, 11.9% of patients treated with Humira and 8.1% of placebo and active 
control − treated patients that had negative baseline anti-nuclear antibody titres reported positive titres at 
Week 24. Two patients out of 3,441 treated with Humira in all rheumatoid arthritis and psoriatic arthritis 
studies developed clinical signs suggestive of new-onset lupus-like syndrome. The patients improved 
following discontinuation of therapy. No patients developed lupus nephritis or central nervous system 
symptoms. 
 
Hepato-biliary events 
 
In controlled Phase 3 trials of Humira in patients with rheumatoid arthritis and psoriatic arthritis with a 
control period duration ranging from 4 to 104 weeks, ALT elevations ≥ 3 x ULN occurred in 3.7% of 
Humira-treated patients and 1.6% of control-treated patients.  
 
In controlled Phase 3 trials of Humira in patients with polyarticular juvenile idiopathic arthritis who were 
4 to 17 years and enthesitis-related arthritis who were 6 to 17 years, ALT elevations ≥ 3 x ULN occurred 
in 6.1% of Humira-treated patients and 1.3% of control-treated patients. Most ALT elevations occurred 
with concomitant methotrexate use. No ALT elevations ≥ 3 x ULN occurred in the Phase 3 trial of Humira 
in patients with polyarticular juvenile idiopathic arthritis who were 2 to < 4 years. 
 



178 

In controlled Phase 3 trials of Humira in patients with Crohn’s disease and ulcerative colitis with a control 
period ranging from 4 to 52 weeks. ALT elevations ≥ 3 x ULN occurred in 0.9% of Humira-treated 
patients and 0.9% of controlled-treated patients.  
 
In the Phase 3 trial of Humira in patients with paediatric Crohn’s disease which evaluated efficacy and 
safety of two body weight adjusted maintenance dose regimens following body weight adjusted induction 
therapy up to 52 weeks of treatment, ALT elevations ≥ 3 x ULN occurred in 2.6%  (5/192) of patients of 
whom 4 were receiving concomitant immunosuppressants at baseline. 
 
In controlled Phase 3 trials of Humira in patients with plaque psoriasis with a control period duration 
ranging from 12 to 24 weeks, ALT elevations ≥ 3 x ULN occurred in 1.8% of Humira-treated patients and 
1.8% of control-treated patients.  
 
No ALT elevations ≥ 3 X ULN occurred in the Phase 3 trial of Humira in paediatric patients with plaque 
psoriasis. 
 
In controlled trials of Humira (initial doses of 160 mg at Week 0 and 80 mg at Week 2, followed by 40 mg 
every week starting at Week 4), in patients with hidradenitis suppurativa with a control period duration 
ranging from 12 to 16 weeks, ALT elevations ≥ 3 x ULN occurred in 0.3% of Humira-treated patients and 
0.6% of control-treated patients. 
 
In controlled trials of Humira (initial doses of 80 mg at Week 0 followed by 40 mg every other week 
starting at Week 1) in adult patients with uveitis up to 80 weeks with a median exposure of 166.5 days and 
105.0 days in Humira-treated and control-treated patients, respectively, ALT elevations ≥ 3 x ULN 
occurred in 2.4% of Humira-treated patients and 2.4% of control-treated patients.  
 
In the controlled Phase 3 trial of Humira in patients with paediatric ulcerative colitis (N=93) which 
evaluated efficacy and safety of a maintenance dose of 0.6 mg/kg (maximum of 40 mg) every other week 
(N=31) and a maintenance dose of 0.6 mg/kg (maximum of 40 mg) every Week (N=32), following body 
weight adjusted induction dosing of 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2 (N=63), or an induction dose of 2.4 mg/kg (maximum of 160 mg) 
at Week 0, placebo at Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2 (N=30), ALT elevations ≥ 
3 X ULN occurred in 1.1% (1/93) of patients. 
 
Across all indications in clinical trials patients with raised ALT were asymptomatic and in most cases 
elevations were transient and resolved on continued treatment.  However, there have also been post-
marketing reports of liver failure as well as less severe liver disorders that may precede liver failure, such 
as hepatitis including autoimmune hepatitis in patients receiving adalimumab. 
 
Concurrent treatment with azathioprine/6-mercaptopurine 
 
In adult Crohn’s disease studies, higher incidences of malignant and serious infection-related adverse 
events were seen with the combination of Humira and azathioprine/6-mercaptopurine compared with 
Humira alone. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important.  It allows 
continued monitoring of the benefit/risk balance of the medicinal product.  Healthcare professionals are 
asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.  
 
4.9 Overdose 
 



179 

No dose-limiting toxicity was observed during clinical trials. The highest dose level evaluated has been 
multiple intravenous doses of 10 mg/kg, which is approximately 15 times the recommended dose.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunosuppressants, Tumour Necrosis Factor alpha (TNF-α) inhibitors. 
ATC code: L04AB04 
 
Mechanism of action 
 
Adalimumab binds specifically to TNF and neutralises the biological function of TNF by blocking its 
interaction with the p55 and p75 cell surface TNF receptors.   
 
Adalimumab also modulates biological responses that are induced or regulated by TNF, including changes 
in the levels of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, and ICAM-1 
with an IC50 of 0.1-0.2 nM).  
 
Pharmacodynamic effects  
 
After treatment with Humira, a rapid decrease in levels of acute phase reactants of inflammation 
(C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) and serum cytokines (IL-6) was 
observed, compared to baseline in patients with rheumatoid arthritis. Serum levels of matrix 
metalloproteinases (MMP-1 and MMP-3) that produce tissue remodelling responsible for cartilage 
destruction were also decreased after Humira administration. Patients treated with Humira usually 
experienced improvement in haematological signs of chronic inflammation. 
 
A rapid decrease in CRP levels was also observed in patients with polyarticular juvenile idiopathic 
arthritis, Crohn’s disease, ulcerative colitis and hidradenitis suppurativa after treatment with Humira. In 
patients with Crohn’s disease, a reduction of the number of cells expressing inflammatory markers in the 
colon including a significant reduction of expression of TNFα was seen. Endoscopic studies in intestinal 
mucosa have shown evidence of mucosal healing in adalimumab treated patients. 
 
Clinical efficacy and safety 
 
Rheumatoid arthritis 
 
Humira was evaluated in over 3,000 patients in all rheumatoid arthritis clinical trials. The efficacy and 
safety of Humira were assessed in five randomised, double-blind and well-controlled studies. Some 
patients were treated for up to 120 months duration. Injection site pain of Humira 40 mg/0.4 ml was 
assessed in two randomised, active control, single-blind, two-period crossover studies.  
 
RA study I evaluated 271 patients with moderately to severely active rheumatoid arthritis who were 
 18 years old, had failed therapy with at least one disease-modifying, anti rheumatic drug and had 
insufficient efficacy with methotrexate at doses of 12.5 to 25 mg (10 mg if methotrexate-intolerant) every 
week and whose methotrexate dose remained constant at 10 to 25 mg every week. Doses of 20, 40 or 
80 mg of Humira or placebo were given every other week for 24 weeks.  
 
RA study II evaluated 544 patients with moderately to severely active rheumatoid arthritis who were 
 18 years old and had failed therapy with at least one disease-modifying, anti-rheumatic drugs.  Doses of 
20 or 40 mg of Humira were given by subcutaneous injection every other week with placebo on alternative 



180 

weeks or every week for 26 weeks; placebo was given every week for the same duration.  No other 
disease-modifying anti-rheumatic drugs were allowed. 
 
RA study III evaluated 619 patients with moderately to severely active rheumatoid arthritis who were 
 18 years old, and who had an ineffective response to methotrexate at doses of 12.5 to 25 mg or have 
been intolerant to 10 mg of methotrexate every week. There were three groups in this study.  The first 
received placebo injections every week for 52 weeks. The second received 20 mg of Humira every week 
for 52 weeks. The third group received 40 mg of Humira every other week with placebo injections on 
alternate weeks. Upon completion of the first 52 weeks, 457 patients enrolled in an open-label extension 
phase in which 40 mg of Humira/MTX was administered every other week up to 10 years. 
 
RA study IV primarily assessed safety in 636 patients with moderately to severely active rheumatoid 
arthritis who were  18 years old. Patients were permitted to be either disease-modifying, anti-rheumatic 
drug-naïve or to remain on their pre-existing rheumatologic therapy provided that therapy was stable for a 
minimum of 28 days. These therapies include methotrexate, leflunomide, hydroxychloroquine, 
sulfasalazine and/or gold salts. Patients were randomised to 40 mg of Humira or placebo every other week 
for 24 weeks.   
 
RA study V evaluated 799 methotrexate-naïve, adult patients with moderate to severely active early 
rheumatoid arthritis (mean disease duration less than 9 months). This study evaluated the efficacy of 
Humira 40 mg every other week/methotrexate combination therapy, Humira 40 mg every other week 
monotherapy and methotrexate monotherapy in reducing the signs and symptoms and rate of progression 
of joint damage in rheumatoid arthritis for 104 weeks. Upon completion of the first 104 weeks, 497 
patients enrolled in an open-label extension phase in which 40 mg of Humira was administered every 
other week up to 10 years. 
 
RA studies VI and VII each evaluated 60 patients with moderately to severely active rheumatoid arthritis 
who were ≥ 18 years old. Enrolled patients were either current users of Humira 40 mg/0.8 ml and rated 
their average injection site pain as at least 3 cm (on a 0-10 cm VAS) or were biologic-naïve subjects who 
were starting Humira 40 mg/0.8 ml. Patients were randomised to receive a single dose of Humira 
40 mg/0.8 ml or Humira 40 mg/0.4 ml, followed by a single injection of the opposite treatment at their 
next dose.  
 
The primary end point in RA studies I, II and III and the secondary endpoint in RA study IV was the 
percent of patients who achieved an ACR 20 response at Week 24 or 26. The primary endpoint in RA 
study V was the percent of patients who achieved an ACR 50 response at Week 52. RA studies III and V 
had an additional primary endpoint at 52 weeks of retardation of disease progression (as detected by X-ray 
results). RA study III also had a primary endpoint of changes in quality of life. The primary endpoint in 
RA studies VI and VII was injection site pain immediately after injection as measured by a 0-10 cm VAS. 
 
ACR response 
 
The percent of Humira-treated patients achieving ACR 20, 50 and 70 responses was consistent across RA 
studies I, II and III. The results for the 40 mg every other week dose are summarised in Table 8.  



181 

 
Table 8  

ACR Responses in Placebo-Controlled Trials 
(Percent of Patients) 

 
Response RA Study Ia** RA Study IIa** RA Study IIIa** 

 
 Placebo/ 

MTXc 
n=60 

Humirab/ MTXc

n=63 
Placebo 
n=110 

Humirab 
n=113 

Placebo/ 
MTXc 
n=200 

Humirab/ MTXc

n=207 

ACR 20    
 6 months 13.3% 65.1% 19.1% 46.0% 29.5% 63.3%
 12 months NA NA NA NA 24.0% 58.9%
ACR 50    
 6 months 6.7% 52.4% 8.2% 22.1% 9.5% 39.1%
 12 months NA NA NA NA 9.5% 41.5%
ACR 70    
 6 months 3.3% 23.8% 1.8% 12.4% 2.5% 20.8%
 12 months NA NA NA NA 4.5% 23.2%
a RA study I at 24 weeks, RA study II at 26 weeks, and RA study III at 24 and 52 weeks 
b 40 mg Humira administered every other week 
c MTX = methotrexate 
**p < 0.01, Humira versus placebo 

 
In RA studies I-IV, all individual components of the ACR response criteria (number of tender and swollen 
joints, physician and patient assessment of disease activity and pain, disability index (HAQ) scores and 
CRP (mg/dl) values) improved at 24 or 26 weeks compared to placebo. In RA study III, these 
improvements were maintained throughout 52 weeks.  
 
In the open-label extension for RA study III, most patients who were ACR responders maintained 
response when followed for up to 10 years. Of 207 patients who were randomised to Humira 40 mg every 
other week, 114 patients continued on Humira 40 mg every other week for 5 years. Among those, 86 
patients (75.4%) had ACR 20 responses; 72 patients (63.2%) had ACR 50 responses; and 41 patients 
(36%) had ACR 70 responses. Of 207 patients, 81 patients continued on Humira 40 mg every other week 
for 10 years. Among those, 64 patients (79.0%) had ACR 20 responses; 56 patients (69.1%) had ACR 50 
responses; and 43 patients (53.1%) had ACR 70 responses. 
 
In RA study IV, the ACR 20 response of patients treated with Humira plus standard of care was 
statistically significantly better than patients treated with placebo plus standard of care (p < 0.001).   
 
In RA studies I-IV, Humira-treated patients achieved statistically significant ACR 20 and 50 responses 
compared to placebo as early as one to two weeks after initiation of treatment. 
 
In RA study V with early rheumatoid arthritis patients who were methotrexate naïve, combination therapy 
with Humira and methotrexate led to faster and significantly greater ACR responses than methotrexate 
monotherapy and Humira monotherapy at Week 52 and responses were sustained at Week 104 (see Table 
9). 



182 

 
Table 9  

ACR Responses in RA Study V 
(percent of patients) 

 

Response 
MTX 
n=257 

Humira 
n=274 

Humira/MTX 
n=268 

p-valuea p-valueb p-valuec 

ACR 20   
 Week 
52 

62.6% 54.4% 72.8% 0.013 < 0.001 0.043 

 Week 
104 

56.0% 49.3% 69.4% 0.002 < 0.001 0.140 

ACR 50   
 Week 
52 

45.9% 41.2% 61.6% < 0.001 < 0.001 0.317 

 Week 
104 

42.8% 36.9% 59.0% < 0.001 < 0.001 0.162 

ACR 70   
 Week 
52 

27.2% 25.9% 45.5% < 0.001 < 0.001 0.656 

 Week 
104 

28.4% 28.1% 46.6% < 0.001 < 0.001 0.864 

a. p-value is from the pairwise comparison of methotrexate monotherapy and Humira/methotrexate 
combination therapy using the Mann-Whitney U test. 

b. p-value is from the pairwise comparison of Humira monotherapy and Humira/methotrexate 
combination therapy using the Mann-Whitney U test 

c.   p-value is from the pairwise comparison of Humira monotherapy and methotrexate monotherapy 
using the Mann-Whitney U test 

 
In the open-label extension for RA study V, ACR response rates were maintained when followed for up to 
10 years. Of 542 patients who were randomised to Humira 40 mg every other week, 170 patients 
continued on Humira 40 mg every other week for 10 years. Among those, 154 patients (90.6%) had ACR 
20 responses; 127 patients (74.7%) had ACR 50 responses; and 102 patients (60.0%) had ACR 70 
responses. 
 
At Week 52, 42.9% of patients who received Humira/methotrexate combination therapy achieved clinical 
remission (DAS28 (CRP) < 2.6) compared to 20.6% of patients receiving methotrexate monotherapy and 
23.4% of patients receiving Humira monotherapy. Humira/methotrexate combination therapy was 
clinically and statistically superior to methotrexate (p < 0.001) and Humira monotherapy (p < 0.001) in 
achieving a low disease state in patients with recently diagnosed moderate to severe rheumatoid arthritis. 
The response for the two monotherapy arms was similar (p = 0.447).  Of 342 subjects originally 
randomized to Humira monotherapy or Humira/methotrexate combination therapy who entered the open-
label extension study, 171 subjects completed 10 years of Humira treatment. Among those, 109 subjects 
(63.7%) were reported to be in remission at 10 years. 
 
Radiographic response 
 
In RA study III, where Humira treated patients had a mean duration of rheumatoid arthritis of 
approximately 11 years, structural joint damage was assessed radiographically and expressed as change in 
modified Total Sharp Score (TSS) and its components, the erosion score and joint space narrowing score.  
Humira/methotrexate patients demonstrated significantly less radiographic progression than patients 
receiving methotrexate alone at 6 and 12 months (see Table 10).   
 



183 

In the open-label extension of RA Study III, the reduction in rate of progression of structural damage is 
maintained for 8 and 10 years in a subset of patients. At 8 years, 81 of 207 patients originally treated with 
40 mg Humira every other week were evaluated radiographically. Among those, 48 patients showed no 
progression of structural damage defined by a change from baseline in the mTSS of 0.5 or less. At 
10 years, 79 of 207 patients originally treated with 40 mg Humira every other week were evaluated 
radiographically. Among those, 40 patients showed no progression of structural damage defined by a 
change from baseline in the mTSS of 0.5 or less. 
 

Table 10 
 Radiographic Mean Changes Over 12 Months in RA Study III 

 
 Placebo/ 

MTXa 
Humira/MTX 
40 mg every 
other week 

Placebo/MTX-
Humira/MTX (95% 

Confidence 
Intervalb)

p-value 

Total Sharp Score 2.7 0.1 2.6 (1.4, 3.8) < 0.001c 

Erosion score 1.6 0.0 1.6 (0.9, 2.2) < 0.001 
JSNd score 1.0 0.1 0.9 (0.3, 1.4)   0.002 

amethotrexate 
b95% confidence intervals for the differences in change scores between methotrexate and Humira.  
cBased on rank analysis  
dJoint Space Narrowing 
 
In RA study V, structural joint damage was assessed radiographically and expressed as change in modified 
Total Sharp Score (see Table 11). 
 

Table 11 
  Radiographic Mean Changes at Week 52 in RA Study V 

 

 

MTX 
n=257 
(95% 

confidence 
interval) 

Humira 
n=274 
(95% 

confidence 
interval)

Humira/MTX 
n=268 
(95% 

confidence 
interval)

p-valuea p-valueb p-valuec 

Total Sharp 
Score 

5.7 (4.2-7.3) 3.0 (1.7-4.3) 1.3 (0.5-2.1) < 0.001 0.0020 < 0.001 

Erosion score 3.7 (2.7-4.7) 1.7 (1.0-2.4) 0.8 (0.4-1.2) < 0.001 0.0082 < 0.001
JSN score 2.0 (1.2-2.8) 1.3 (0.5-2.1) 0.5 (0-1.0) < 0.001 0.0037 0.151

a p-value is from the pairwise comparison of methotrexate monotherapy and Humira/methotrexate 
combination therapy using the Mann-Whitney U test. 

b p-value is from the pairwise comparison of Humira monotherapy and Humira/methotrexate 
combination therapy using the Mann-Whitney U test  

c p-value is from the pairwise comparison of Humira monotherapy and methotrexate monotherapy 
using the Mann-Whitney U test 

 
Following 52 weeks and 104 weeks of treatment, the percentage of patients without progression (change 
from baseline in modified Total Sharp Score  0.5) was significantly higher with Humira/methotrexate 
combination therapy (63.8% and 61.2% respectively) compared to methotrexate monotherapy (37.4% and 
33.5% respectively, p < 0.001) and Humira monotherapy (50.7%, p < 0.002 and 44.5%, p < 0.001 
respectively). 
 
In the open-label extension of RA study V, the mean change from baseline at Year 10 in the modified 
Total Sharp Score was 10.8, 9.2 and 3.9 in patients originally randomized to methotrexate monotherapy, 



184 

Humira monotherapy and Humira/methotrexate combination therapy, respectively. The corresponding 
proportions of patients with no radiographic progression were 31.3%, 23.7% and 36.7% respectively. 
 
Quality of life and physical function  
 
Health-related quality of life and physical function were assessed using the disability index of the Health 
Assessment Questionnaire (HAQ) in the four original adequate and well-controlled trials, which was a 
pre-specified primary endpoint at Week 52 in RA study III. All doses/schedules of Humira in all four 
studies showed statistically significantly greater improvement in the disability index of the HAQ from 
baseline to Month 6 compared to placebo and in RA study III the same was seen at Week 52. Results from 
the Short Form Health Survey (SF 36) for all doses/schedules of Humira in all four studies support these 
findings, with statistically significant physical component summary (PCS) scores, as well as statistically 
significant pain and vitality domain scores for the 40 mg every other week dose. A statistically significant 
decrease in fatigue as measured by functional assessment of chronic illness therapy (FACIT) scores was 
seen in all three studies in which it was assessed (RA studies I, III, IV). 
 
In RA study III, most subjects who achieved improvement in physical function and continued treatment 
maintained improvement through Week 520 (120 months) of open-label treatment. Improvement in 
quality of life was measured up to Week 156 (36 months) and improvement was maintained through that 
time. 
 
In RA study V, the improvement in the HAQ disability index and the physical component of the SF 36 
showed greater improvement (p < 0.001) for Humira/methotrexate combination therapy versus 
methotrexate monotherapy and Humira monotherapy at Week 52, which was maintained through 
Week 104. Among the 250 subjects who completed the open-label extension study, improvements in 
physical function were maintained through 10 years of treatment. 
 
Injection site pain 
 
For the pooled crossover RA studies VI and VII, a statistically significant difference for injection site pain 
immediately after dosing was observed between Humira 40 mg/0.8 ml and Humira 40 mg/0.4 ml (mean 
VAS of 3.7 cm versus 1.2 cm, scale of 0-10 cm, P < 0.001).  This represented an 84% median reduction in 
injection site pain. 
 
Axial spondyloarthritis  
 
Ankylosing spondylitis (AS) 
 
Humira 40 mg every other week was assessed in 393 patients in two randomised, 24 week double − blind, 
placebo − controlled studies in patients with active ankylosing spondylitis (mean baseline score of disease 
activity [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)] was 6.3 in all groups) who have 
had an inadequate response to conventional therapy. Seventy-nine (20.1%) patients were treated 
concomitantly with disease modifying anti − rheumatic drugs, and 37 (9.4%) patients with 
glucocorticoids. The blinded period was followed by an open − label period during which patients 
received Humira 40 mg every other week subcutaneously for up to an additional 28 weeks. Subjects 
(n=215, 54.7%) who failed to achieve ASAS 20 at Weeks 12, or 16 or 20 received early escape open-label 
adalimumab 40 mg every other week subcutaneously and were subsequently treated as non-responders in 
the double-blind statistical analyses. 
 
In the larger AS study I with 315 patients, results showed statistically significant improvement of the signs 
and symptoms of ankylosing spondylitis in patients treated with Humira compared to placebo.  Significant 
response was first observed at Week 2 and maintained through 24 weeks (Table 12).  
 



185 

Table 12 
 Efficacy Responses in Placebo-Controlled AS Study – Study I 

Reduction of Signs and Symptoms 
 

Response Placebo 
N=107 

Humira 
N=208 

ASASa 20 
             Week 2 16% 42%*** 

Week 12 21% 58%*** 
Week 24 19% 51%*** 

ASAS 50 
             Week 2 3% 16%*** 

Week 12 10% 38%*** 
Week 24 11% 35%*** 

ASAS 70 
             Week 2 0% 7%** 

Week 12 5% 23%*** 
Week 24 8% 24%*** 

 
BASDAIb 50 
             Week 2 4% 20%*** 

Week 12  16% 45%*** 
Week 24  15% 42%*** 

***,** Statistically significant at p < 0.001, < 0.01 for all comparisons between Humira and 
placebo at Weeks 2, 12 and  24 
a Assessments in Ankylosing Spondylitis 
b Bath Ankylosing Spondylitis Disease Activity Index 

 
Humira treated patients had significantly greater improvement at Week 12 which was maintained through 
Week 24 in both the SF36 and Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL). 
 
Similar trends (not all statistically significant) were seen in the smaller randomised, double − blind, 
placebo controlled AS study II of 82 adult patients with active ankylosing spondylitis. 
 
Axial spondyloarthritis without radiographic evidence of AS 
 
The safety and efficacy of Humira were assessed in two randomized, double-blind placebo controlled 
studies in patients with non-radiographic axial spondyloarthritis (nr-axSpA). Study nr-axSpA I evaluated 
patients with active nr-axSpA. Study nr-axSpA II was a treatment withdrawal study in active nr-axSpA 
patients who achieved remission during open-label treatment with Humira. 
 
Study nr-axSpA I 
 
In Study nr-axSpA I, Humira 40 mg every other week was assessed in 185 patients in a randomised, 
12 week double - blind, placebo - controlled study in patients with active nr-axSpA (mean baseline score 
of disease activity [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)] was 6.4 for patients 
treated with Humira and 6.5 for those on placebo) who have had an inadequate response to or intolerance 
to  1 NSAIDs, or a contraindication for NSAIDs. 
 
Thirty-three (18%)  patients were treated concomitantly with disease modifying anti-rheumatic drugs, and 
146 (79%) patients with NSAIDs at baseline. The double-blind period was followed by an open-label 
period during which patients receive Humira 40 mg every other week subcutaneously for up to an 



186 

additional 144 weeks. Week 12 results showed statistically significant improvement of the signs and 
symptoms of active nr-axSpA in patients treated with Humira compared to placebo (Table 13). 
 

Table 13 
Efficacy Response in Placebo-Controlled Study nr-axSpA I 

 
Double-Blind 
Response at Week 12 

Placebo 
N=94 

Humira 
N=91 

ASASa 40 15% 36%***
ASAS 20 31% 52%**
ASAS 5/6 6% 31%***
ASAS Partial Remission 5%   16%*
BASDAIb 50 15%    35%**
ASDASc,d,e -0.3 -1.0***
ASDAS Inactive Disease 4% 24%***
hs-CRPd,f,g -0.3 -4.7***
SPARCCh MRI Sacroiliac Jointsd,i -0.6 -3.2**
SPARCC MRI Spined,j -0.2 -1.8**
a Assessment of SpondyloArthritis international Society 
b Bath Ankylosing Spondylitis Disease Activity Index 
c Ankylosing Spondylitis Disease Activity Score 

d mean change from baseline 
e n=91 placebo and n=87 Humira 
f high sensitivity C-Reactive Protein (mg/L) 
g n=73 placebo and n=70 Humira 
h Spondyloarthritis Research Consortium of Canada 
i n=84 placebo and Humira 
j n=82 placebo and n=85 Humira 
***, **, * Statistically significant at p < 0.001, < 0.01, and  < 0.05, respectively, for all comparisons 
between Humira and placebo. 
 
In the open-label extension, improvement in the signs and symptoms was maintained with Humira 
therapy through Week 156. 
 
Inhibition of inflammation 
 
Significant improvement of signs of inflammation as measured by hs-CRP and MRI of both Sacroiliac 
Joints and the Spine was maintained in Humira-treated patients through Week 156 and Week 104, 
respectively. 
 
Quality of life and physical function 

 
Health-related quality of life and physical function were assessed using the HAQ-S and the SF-36 
questionnaires. Humira showed statistically significantly greater improvement in the HAQ-S total score 
and the SF-36 Physical Component Score (PCS) from baseline to Week 12 compared to placebo. 
Improvement in health-related quality of life and physical function was maintained during the open-label 
extension through Week 156. 
 
Study nr-axSpA II 
 
673 patients with active nr-axSpA (mean baseline disease activity [BASDAI] was 7.0) who had an 
inadequate response to  2 NSAIDs, or an intolerance to or a contraindication for NSAIDs enrolled into 
the open-label period of Study nr-axSpA II during which they received Humira 40 mg eow for 28 weeks. 



187 

These patients also had objective evidence of inflammation in the sacroiliac joints or spine on MRI or 
elevated hs-CRP. Patients who achieved sustained remission for at least 12 weeks (N=305) (ASDAS < 1.3 
at Weeks 16, 20, 24, and 28) during the open-label period were then randomized to receive either 
continued treatment with Humira 40 mg eow (N=152) or placebo (N=153) for an additional 40 weeks in a 
double-blind, placebo-controlled period (total study duration 68 weeks). Subjects who flared during the 
double-blind period were allowed Humira 40 mg eow rescue therapy for at least 12 weeks. 
 
The primary efficacy endpoint was the proportion of patients with no flare by Week 68 of the study. Flare 
was defined as ASDAS ≥ 2.1 at two consecutive visits four weeks apart. A greater proportion of patients 
on Humira had no disease flare during the double-blind period, when compared with those on placebo 
(70.4% vs. 47.1%, p<0.001) (Figure 1). 

 
Figure 1: Kaplan-Meier Curves Summarizing Time to Flare in 

Study nr-axSpA II 

   
   

   
   

   
   

 P
R

O
B

A
B

IL
IT

Y
 O

F
 N

O
 F

L
A

R
E

 

 TIME (WEEKS) 
                                  Treatment        Placebo     Humira     ∆ Censored

 
Note: P = Placebo (Number at Risk (flared)); A = HUMIRA (Number at Risk (flared)). 
 
Among the 68 patients who flared in the group allocated to treatment withdrawal, 65 completed 12 weeks 
of rescue therapy with Humira, out of which 37 (56.9%) had regained remission (ASDAS < 1.3) after 
12 weeks of restarting the open-label treatment.  
 
By Week 68, patients receiving continuous Humira treatment showed statistically significant greater 
improvement of the signs and symptoms of active nr-axSpA as compared to patients allocated to treatment 
withdrawal during the double-blind period of the study (Table 14). 
 



188 

Table 14 
Efficacy Response in Placebo-Controlled Period for Study nr-axSpA II 

 
Double-Blind 
Response at Week 68 

Placebo 
N=153 

Humira 
N=152 

ASASa,b 20 47.1% 70.4%***
ASASa,b 40 45.8% 65.8%***
ASASa Partial Remission 26.8% 42.1%**
ASDASc Inactive Disease 33.3% 57.2%***
Partial Flared 64.1% 40.8%***
a Assessment of SpondyloArthritis international Society 
b Baseline is defined as open label baseline when patients have active disease. 
c Ankylosing Spondylitis Disease Activity Score 

d Partial flare is defined as ASDAS ≥ 1.3 but < 2.1 at 2 consecutive visits. 
***, ** Statistically significant at p < 0.001 and < 0.01, respectively, for all comparisons between 
Humira and placebo. 

 
Psoriatic arthritis 
 
Humira, 40 mg every other week, was studied in patients with moderately to severely active psoriatic 
arthritis in two placebo-controlled studies, PsA studies I and II.  PsA study I with 24 week duration, 
treated 313 adult patients who had an inadequate response to non-steroidal anti-inflammatory drug therapy 
and of these, approximately 50% were taking methotrexate. PsA study II with 12-week duration, treated 
100 patients who had an inadequate response to DMARD therapy. Upon completion of both studies, 383 
patients enrolled in an open-label extension study, in which 40 mg Humira was administered every other 
week. 
 
There is insufficient evidence of the efficacy of Humira in patients with ankylosing spondylitis-like 
psoriatic arthropathy due to the small number of patients studied.  
 

Table 15 
ACR Response in Placebo-Controlled Psoriatic Arthritis Studies 

(Percent of Patients) 
 

 PsA Study I PsA Study II 

Response 
Placebo 
N=162

Humira 
N=151

Placebo  
N=49

Humira 
N=51 

ACR 20    
 Week 12 14% 58%*** 16% 39%* 
 Week 24 15% 57%*** N/A N/A 
ACR 50    
 Week 12 4% 36%*** 2% 25%*** 
 Week 24 6% 39%*** N/A N/A 
ACR 70    
 Week 12 1% 20%*** 0% 14% * 
 Week 24 1% 23%*** N/A N/A 
*** p < 0.001 for all comparisons between Humira and placebo 
* p < 0.05 for all comparisons between Humira and placebo 
N/A  not applicable 

 
ACR responses in PsA study I were similar with and without concomitant methotrexate therapy. 
ACR responses were maintained in the open-label extension study for up to 136 weeks. 

 



189 

Radiographic changes were assessed in the psoriatic arthritis studies. Radiographs of hands, wrists, and 
feet were obtained at baseline and Week 24 during the double-blind period when patients were on Humira 
or placebo and at Week 48 when all patients were on open-label Humira. A modified Total Sharp Score 
(mTSS), which included distal interphalangeal joints (i.e. not identical to the TSS used for rheumatoid 
arthritis), was used. 
 
Humira treatment reduced the rate of progression of peripheral joint damage compared with placebo 
treatment as measured by change from baseline in mTSS  (mean ± SD) 0.8 ± 2.5 in the placebo group (at 
Week 24) compared with 0.0 ± 1.9; (p< 0.001) in the Humira group (at Week 48). 
 
In subjects treated with Humira with no radiographic progression from baseline to Week 48 (n=102), 84% 
continued to show no radiographic progression through 144 weeks of treatment. 
Humira treated patients demonstrated statistically significant improvement in physical function as assessed 
by HAQ and Short Form Health Survey (SF 36) compared to placebo at Week 24. Improved physical 
function continued during the open label extension up to Week 136. 
 
Psoriasis  
 
The safety and efficacy of Humira were studied in adult patients with chronic plaque psoriasis ( 10% 
BSA involvement and Psoriasis Area and Severity Index (PASI)  12 or  10) who were candidates for 
systemic therapy or phototherapy in randomised, double-blind studies. 73% of patients enrolled in 
Psoriasis Studies I and II had received prior systemic therapy or phototherapy.  The safety and efficacy of 
Humira were also studied in adult patients with moderate to severe chronic plaque psoriasis with 
concomitant hand and/or foot psoriasis who were candidates for systemic therapy in a randomised double-
blind study (Psoriasis Study III).   
 
Psoriasis Study I (REVEAL) evaluated 1,212 patients within three treatment periods.  In period A, patients 
received placebo or Humira at an initial dose of 80 mg followed by 40 mg every other week starting one 
week after the initial dose. After 16 weeks of therapy, patients who achieved at least a PASI 75 response 
(PASI score improvement of at least 75% relative to baseline), entered period B and received open-label 
40 mg Humira every other week. Patients who maintained PASI 75 response at Week 33 and were 
originally randomised to active therapy in Period A, were re-randomised in period C to receive 40 mg 
Humira every other week or placebo for an additional 19 weeks. Across all treatment groups, the mean 
baseline PASI score was 18.9 and the baseline Physician’s Global Assessment (PGA) score ranged from 
“moderate” (53% of subjects included) to “severe” (41%) to “very severe” (6%). 
 
Psoriasis Study II (CHAMPION) compared the efficacy and safety of Humira versus methotrexate and 
placebo in 271 patients. Patients received placebo, an initial dose of MTX 7.5 mg and thereafter dose 
increases up to Week 12, with a maximum dose of 25 mg or an initial dose of 80 mg Humira followed by 
40 mg every other week (starting one week after the initial dose) for 16 weeks. There are no data available 
comparing Humira and MTX beyond 16 weeks of therapy. Patients receiving MTX who achieved a 
PASI 50 response at Week 8 and/or 12 did not receive further dose increases. Across all treatment 
groups, the mean baseline PASI score was 19.7 and the baseline PGA score ranged from “mild” (<1%) to 
“moderate” (48%) to “severe” (46%) to “very severe” (6%). 
 
Patients participating in all Phase 2 and Phase 3 psoriasis studies were eligible to enrol into an open-label 
extension trial, where Humira was given for at least an additional 108 weeks. 
 
In Psoriasis Studies I and II, a primary endpoint was the proportion of patients who achieved a PASI 75 
response from baseline at Week 16 (see Tables 16 and 17). 



190 

 
Table 16 

Ps Study I (REVEAL)  - Efficacy Results at 16 Weeks 

 
Placebo 
N=398 
n (%) 

Humira 40 mg eow 
N=814 
n (%) 

     PASI 75a 26 (6.5) 578 (70.9)b 
    PASI 100 3 (0.8) 163 (20.0)b 
    PGA: Clear/minimal 17 (4.3) 506 (62.2)b 
a Percent of patients achieving PASI75 response was calculated as centre-
adjusted rate 
b p < 0.001, Humira vs. placebo

 

Table 17 
 Ps Study II (CHAMPION) Efficacy Results at 16 Weeks 
 Placebo 

N=53 
n (%) 

MTX 
N=110 
n (%) 

Humira 40 mg eow 
N=108 
n (%) 

     PASI 75 10 (18.9) 39 (35.5) 86 (79.6) a, b 
    PASI 100 1 (1.9) 8 (7.3) 18 (16.7) c, d 
    PGA: 
Clear/minimal 

6 (11.3) 33 (30.0) 79 (73.1) a, b 

a p < 0.001 Humira vs. placebo 
b p < 0.001 Humira vs. methotrexate 
c p < 0.01 Humira vs. placebo 
d p < 0.05 Humira vs. methotrexate

 
In Psoriasis Study I, 28% of patients who were PASI 75 responders and were re-randomised to placebo at 
Week 33 compared to 5% continuing on Humira, p < 0.001, experienced “loss of adequate response” 
(PASI score after Week 33 and on or before Week 52 that resulted in a <PASI 50 response relative to 
baseline with a minimum of a 6-point increase in PASI score relative to Week 33). Of the patients who 
lost adequate response after re-randomisation to placebo who then enrolled into the open-label extension 
trial, 38% (25/66) and 55% (36/66) regained PASI 75 response after 12 and 24 weeks of re-treatment, 
respectively. 
 
A total of 233 PASI 75 responders at Week 16 and Week 33 received continuous Humira therapy for 
52 weeks in Psoriasis Study I, and continued Humira in the open-label extension trial.  PASI 75 and PGA 
of clear or minimal response rates in these patients were 74.7% and 59.0%, respectively, after an 
additional 108 weeks of open-label therapy (total of 160 weeks). In an analysis in which all patients who 
dropped out of the study for adverse events or lack of efficacy, or who dose-escalated, were considered 
non-responders, PASI 75 and PGA of clear or minimal response rates in these patients were 69.6% and 
55.7%, respectively, after an additional 108 weeks of open-label therapy (total of 160 weeks). 
 
A total of 347 stable responders participated in a withdrawal and retreatment evaluation in an open-label 
extension study. During the withdrawal period, symptoms of psoriasis returned over time with a median 
time to relapse (decline to PGA “moderate” or worse) of approximately 5 months. None of these patients 
experienced rebound during the withdrawal period. A total of 76.5% (218/285) of patients who entered the 
retreatment period had a response of PGA “clear” or “minimal” after 16 weeks of retreatment, irrespective 
of whether they relapsed during withdrawal (69.1%[123/178] and 88.8% [95/107] for patients who 
relapsed and who did not relapse during the withdrawal period, respectively).  A similar safety profile was 
observed during retreatment as before withdrawal. 
 



191 

Significant improvements at Week 16 from baseline compared to placebo (Studies I and II) and MTX 
(Study II) were demonstrated in the DLQI (Dermatology Life Quality Index). In Study I, improvements in 
the physical and mental component summary scores of the SF-36 were also significant compared to 
placebo. 
 
In an open-label extension study, for patients who dose escalated from 40 mg every other week to 40 mg 
weekly due to a PASI response below 50%, 26.4% (92/349) and 37.8% (132/349) of patients achieved 
PASI 75 response at Week 12 and 24, respectively. 
 
Psoriasis Study III (REACH) compared the efficacy and safety of Humira versus placebo in 72 patients 
with moderate to severe chronic plaque psoriasis and hand and/or foot psoriasis. Patients received an 
initial dose of 80 mg Humira followed by 40 mg every other week (starting one week after the initial dose) 
or placebo for 16 weeks. At Week 16, a statistically significantly greater proportion of patients who 
received Humira achieved PGA of 'clear' or 'almost clear' for the hands and/or feet compared to patients 
who received placebo (30.6% versus 4.3%, respectively [P = 0.014]). 
 
Psoriasis Study IV compared efficacy and safety of Humira versus placebo in 217 adult patients with 
moderate to severe nail psoriasis. Patients received an initial dose of 80 mg Humira followed by 40 mg 
every other week (starting one week after the initial dose) or placebo for 26 weeks followed by open-label 
Humira treatment for an additional 26 weeks. Nail psoriasis assessments included the Modified Nail 
Psoriasis Severity Index (mNAPSI), the Physician’s Global Assessment of Fingernail Psoriasis (PGA-F) 
and the Nail Psoriasis Severity Index (NAPSI) (see Table 18). Humira demonstrated a treatment benefit in 
nail psoriasis patients with different extents of skin involvement (BSA≥10% (60% of patients) and 
BSA<10% and ≥5% (40% of patients)). 
 

Table 18: Ps Study IV Efficacy Results at 16, 26 and 52 Weeks 
Endpoint Week 16 

Placebo-Controlled
Week 26 

Placebo-Controlled
Week 52 

Open-label
Placebo 
N=108 

Humira 
40 mg eow 

N=109

Placebo
N=108 

Humira 
40 mg eow 

N=109

Humira 
40 mg eow  

N=80 
≥ mNAPSI 75 (%) 2.9 26.0a 3.4 46.6a 65.0 
PGA-F clear/minimal and 
≥2-grade improvement (%) 

2.9 29.7a 6.9 48.9a 61.3 

Percent Change in Total 
Fingernail NAPSI (%) 

-7.8 -44.2 a -11.5 -56.2a -72.2 

a p<0.001, Humira vs. placebo  
 
Humira treated patients showed statistically significant improvements at Week 26 compared with placebo 
in the DLQI.  
 
 
Hidradenitis suppurativa 
 
The safety and efficacy of Humira were assessed in randomised, double-blind, placebo-controlled studies 
and an open-label extension study in adult patients with moderate to severe hidradenitis suppurativa (HS) 
who were intolerant, had a contraindication or an inadequate response to at least a 3-month trial of 
systemic antibiotic therapy.  The patients in HS-I and HS-II had Hurley Stage II or III disease with at least 
3 abscesses or inflammatory nodules. 
 
Study HS-I (PIONEER I) evaluated 307 patients with 2 treatment periods.  In Period A, patients received 
placebo or Humira at an initial dose of 160 mg at Week 0, 80 mg at Week 2, and 40 mg every week 
starting at Week 4 to Week 11.  Concomitant antibiotic use was not allowed during the study.  After 



192 

12 weeks of therapy, patients who had received Humira in Period A were re-randomised in Period B to 1 
of 3 treatment groups (Humira 40 mg every week, Humira 40 mg every other week, or placebo from Week 
12 to Week 35).  Patients who had been randomised to placebo in Period A were assigned to receive 
Humira 40 mg every week in Period B. 
 
Study HS-II (PIONEER II) evaluated 326 patients with 2 treatment periods.  In Period A, patients received 
placebo or Humira at an initial dose of 160 mg at Week 0 and 80 mg at Week 2 and 40 mg every week 
starting at Week 4 to Week 11.  19.3% of patients had continued baseline oral antibiotic therapy during the 
study.  After 12 weeks of therapy, patients who had received Humira in Period A were re-randomised in 
Period B to 1 of 3 treatment groups (Humira 40 mg every week, Humira 40 mg every other week, or 
placebo from Week 12 to Week 35).  Patients who had been randomised to placebo in Period A were 
assigned to receive placebo in Period B. 
 
Patients participating in Studies HS-I and HS-II were eligible to enrol into an open-label extension study 
in which Humira 40mg was administered every week. Mean exposure in all adalimumab population was 
762 days.  Throughout all 3 studies patients used topical antiseptic wash daily. 
 
Clinical Response 
 
Reduction of inflammatory lesions and prevention of worsening of abscesses and draining fistulas was 
assessed using Hidradenitis Suppurativa Clinical Response (HiSCR; at least a 50% reduction in total 
abscess and inflammatory nodule count with no increase in abscess count and no increase in draining 
fistula count relative to Baseline).  Reduction in HS-related skin pain was assessed using a Numeric 
Rating Scale in patients who entered the study with an initial baseline score of 3 or greater on a 11 point 
scale.  
 
At Week 12, a significantly higher proportion of patients treated with Humira versus placebo achieved 
HiSCR.   At Week 12, a significantly higher proportion of patients in Study HS-II experienced a clinically 
relevant decrease in HS-related skin pain (see Table 19).  Patients treated with Humira had significantly 
reduced risk of disease flare during the initial 12 weeks of treatment. 
 

Table 19:  Efficacy Results at 12 Weeks, HS Studies I and II 

 

HS Study I HS Study II 

Placebo
Humira 40 mg 

Weekly Placebo  
Humira 40 mg 

Weekly 

Hidradenitis Suppurativa 
Clinical Response (HiSCR)a   

N = 154 
40 (26.0%) 

N = 153 
64 (41.8%) * 

N=163 
45 (27.6%) 

N=163 
96 (58.9%) *** 

≥30% Reduction in Skin 
Painb 

N = 109 
27 (24.8%)

N = 122 
34 (27.9%)

N=111 
23 (20.7%) 

N=105 
48 (45.7%) ***

* P < 0.05, ***P < 0.001, Humira versus placebo  
a Among all randomised patients. 
b Among patients with baseline HS-related skin pain assessment ≥ 3, based on Numeric Rating 

Scale 0 – 10; 0 = no skin pain, 10 = skin pain as bad as you can imagine.
 
Treatment with Humira 40 mg every week significantly reduced the risk of worsening of abscesses and 
draining fistulas.  Approximately twice the proportion of patients in the placebo group in the first 12 
weeks of Studies HS-I and HS-II, compared with those in the Humira group experienced worsening of 
abscesses (23.0% vs 11.4%, respectively) and draining fistulas (30.0% vs 13.9%, respectively). 
 
Greater improvements at Week 12 from baseline compared to placebo were demonstrated in skin-specific 
health-related quality of life, as measured by the Dermatology Life Quality Index (DLQI; Studies HS-I 



193 

and HS-II), patient global satisfaction with medication treatment as measured by the Treatment 
Satisfaction Questionnaire - medication (TSQM; Studies HS-I and HS-II), and physical health as 
measured by the physical component summary score of the SF-36 (Study HS-I). 
 
In patients with at least a partial response to Humira 40 mg weekly at Week 12, the HiSCR rate at Week 
36 was higher in patients who continued weekly Humira than in patients in whom dosing frequency was 
reduced to every other week, or in whom treatment was withdrawn (see Table 20).   
 

Table 20:  Proportion of Patientsa Achieving HiSCRb at Weeks 24 and 36 After  
Treatment Reassignment from Weekly Humira at Week 12 

 

Placebo 
(treatment 

withdrawal) 
N = 73 

Humira 40 mg 
every other week 

N = 70 

Humira 40 mg 
weekly 
N = 70 

Week 24 24 (32.9%) 36 (51.4%) 40 (57.1%) 

Week 36 22 (30.1%) 28 (40.0%) 39 (55.7%) 
a Patients with at least a partial response to Humira 40 mg weekly after 12 

weeks of treatment. 
b Patients meeting protocol-specified criteria for loss of response or no 

improvement were required to discontinue from the studies and were 
counted as nonresponders.

 
Among patients who were at least partial responders at Week 12, and who received continuous weekly 
Humira therapy, the HiSCR rate at Week 48 was 68.3% and at Week 96 was 65.1%. Longer term 
treatment with Humira 40 mg weekly for 96 weeks identified no new safety findings. 
 
Among patients whose Humira treatment was withdrawn at Week 12 in Studies HS-I and HS-II, the 
HiSCR rate 12 weeks after re-introduction of Humira 40 mg weekly returned to levels similar to that 
observed before withdrawal (56.0 %). 
 
Crohn’s disease 
 
The safety and efficacy of Humira were assessed in over 1500 patients with moderately to severely active 
Crohn’s disease (Crohn’s Disease Activity Index (CDAI)  220 and  450) in randomised, double-blind, 
placebo-controlled studies. Concomitant stable doses of aminosalicylates, corticosteroids, and/or 
immunomodulatory agents were permitted and 80% of patients continued to receive at least one of these 
medications.  
 
Induction of clinical remission (defined as CDAI < 150) was evaluated in two studies, CD Study I 
(CLASSIC I) and CD Study II (GAIN). In CD Study I, 299 TNF-antagonist naive patients were 
randomised to one of four treatment groups; placebo at Weeks 0 and 2, 160 mg Humira at Week 0 and 
80 mg at Week 2, 80 mg at Week 0 and 40 mg at Week 2, and 40 mg at Week 0 and 20 mg at Week 2. In 
CD Study II, 325 patients who had lost response or were intolerant to infliximab were randomised to 
receive either 160 mg Humira at Week 0 and 80 mg at Week 2 or placebo at Weeks 0 and 2. The primary 
non-responders were excluded from the studies and therefore these patients were not further evaluated. 
 
Maintenance of clinical remission was evaluated in CD study III (CHARM).  In CD Study III, 854 patients 
received open-label 80 mg at Week 0 and 40 mg at Week 2.  At Week 4 patients were randomised to 
40 mg every other week, 40 mg every week, or placebo with a total study duration of 56 weeks. Patients in 
clinical response (decrease in CDAI ≥ 70) at Week 4 were stratified and analysed separately from those 
not in clinical response at Week 4.  Corticosteroid taper was permitted after Week 8.  
 



194 

CD study I and CD study II induction of remission and response rates are presented in Table 21. 
 

Table 21 
Induction of Clinical Remission and Response 

(Percent of Patients) 

 CD Study I: Infliximab Naive 
Patients 

CD Study II: Infliximab 
Experienced Patients 

 Placebo 
N=74 

Humira 
80/40 mg 

N = 75 

Humira  
160/80 mg 

N=76 

Placebo 
N=166 

Humira  
160/80 mg 

N=159 

Week 4      

Clinical remission 12% 24% 36%* 7% 21%* 

Clinical response (CR-
100) 

24% 37% 49%** 25% 38%** 

All p-values are pairwise comparisons of proportions for Humira versus placebo 
* p < 0.001 
** p < 0.01 

 
Similar remission rates were observed for the 160/80 mg and 80/40 mg induction regimens by Week 8 and 
adverse events were more frequently noted in the 160/80 mg group. 
 
In CD Study III, at Week 4, 58% (499/854) of patients were in clinical response and were assessed in the 
primary analysis. Of those in clinical response at Week 4, 48% had been previously exposed to other TNF-
antagonists. Maintenance of remission and response rates are presented in Table 22.  Clinical remission 
results remained relatively constant irrespective of previous TNF-antagonist exposure. 
 
Disease-related hospitalisations and surgeries were statistically significantly reduced with adalimumab 
compared with placebo at Week 56. 



195 

 
Table 22 

Maintenance of Clinical Remission and Response 
(Percent of Patients) 

 Placebo 40 mg Humira 
every other week 

40 mg Humira
every week 

Week 26 N=170 N=172 N=157 

Clinical remission 17% 40%* 47%* 

Clinical response (CR-100) 27% 52%* 52%* 

Patients in steroid-free remission  
for >=90 daysa 

3% (2/66) 19% (11/58)** 15% (11/74)** 

Week 56 N=170 N=172 N=157 

Clinical remission 12% 36%* 41%* 

Clinical response (CR-100) 17% 41%* 48%* 

Patients in steroid-free remission  
for > = 90 daysa 

5% (3/66) 29% (17/58)* 20% (15/74)** 

* p < 0.001 for Humira versus placebo pairwise comparisons of proportions 
** p < 0.02 for Humira versus placebo pairwise comparisons of proportions 
a Of those receiving corticosteroids at baseline 

 
Among patients who were not in response at Week 4, 43% of Humira maintenance patients responded by 
Week 12 compared to 30% of placebo maintenance patients. These results suggest that some patients who 
have not responded by Week 4 benefit from continued maintenance therapy through Week 12.  Therapy 
continued beyond 12 weeks did not result in significantly more responses (see section 4.2).   
 
117/276 patients from CD study I and 272/777 patients from CD studies II and III were followed through 
at least 3 years of open-label adalimumab therapy.  88 and 189 patients, respectively, continued to be in 
clinical remission.  Clinical response (CR-100) was maintained in 102 and 233 patients, respectively. 
 
Quality of life 
 
In CD Study I and CD Study II, statistically significant improvement in the disease-specific inflammatory 
bowel disease questionnaire (IBDQ) total score was achieved at Week 4 in patients randomised to Humira 
80/40 mg and 160/80 mg compared to placebo and was seen at Weeks 26 and 56 in CD Study III as well 
among the adalimumab treatment groups compared to the placebo group. 
 
Ulcerative colitis 
 
The safety and efficacy of multiple doses of Humira were assessed in adult patients with moderately to 
severely active ulcerative colitis (Mayo score 6 to 12 with endoscopy subscore of 2 to 3) in randomised, 
double-blind, placebo-controlled studies.  
 
In study UC-I, 390 TNF-antagonist naïve patients were randomised to receive either placebo at Weeks 0 
and 2, 160 mg Humira at Week 0 followed by 80 mg at Week 2, or 80 mg Humira at Week 0 followed by 
40 mg at Week 2.  After Week 2, patients in both adalimumab arms received 40 mg eow.  Clinical 
remission (defined as Mayo score ≤ 2 with no subscore > 1) was assessed at Week 8.  
 
In study UC-II, 248 patients received 160 mg of Humira at Week 0, 80 mg at Week 2 and 40 mg eow 
thereafter, and 246 patients received placebo. Clinical results were assessed for induction of remission at 
Week 8 and for maintenance of remission at Week 52.  



196 

 
Patients induced with 160/80 mg Humira achieved clinical remission versus placebo at Week 8 in 
statistically significantly greater percentages in study UC-I (18% vs. 9% respectively, p=0.031) and study 
UC-II (17% vs. 9% respectively, p=0.019). In study UC-II, among those treated with Humira who were in 
remission at Week 8, 21/41 (51%) were in remission at Week 52. 
 
Results from the overall UC-II study population are shown in Table 23. 
 

Table 23 
Response, Remission and Mucosal Healing in Study UC-II 

(Percent of Patients) 
 Placebo

 
Humira 40 mg  

eow 

Week 52 N=246 N=248 
  Clinical Response  18%   30%* 

  Clinical Remission 9%   17%* 
  Mucosal Healing  15%   25%* 
  Steroid-free remission for ≥ 90 days a  6%  

(N=140) 
     13% * 
(N=150) 

Week 8 and 52 
  Sustained Response  12%   24%** 
  Sustained Remission  4%   8%* 
  Sustained Mucosal Healing  11%  19%* 
Clinical remission is Mayo score  ≤ 2 with no subscore > 1; 
Clinical response is decrease from baseline in Mayo score ≥ 3 points and ≥ 30% plus a 
decrease in the rectal bleeding subscore [RBS] ≥ 1 or an absolute RBS of 0 or 1; 
*p < 0.05 for Humira vs. placebo pairwise comparison of proportions  
**p < 0.001 for Humira vs. placebo pairwise comparison of proportions 
a   Of those receiving corticosteroids at baseline 
 
Of those patients who had a response at Week 8, 47% were in response, 29% were in remission, 41% had 
mucosal healing, and 20% were in steroid-free remission for ≥ 90 days at Week 52. 
 
Approximately 40% of patients in study UC-II had failed prior anti-TNF treatment with infliximab. The 
efficacy of adalimumab in those patients was reduced compared to that in anti-TNF naïve patients.  
Among patients who had failed prior anti-TNF treatment, Week 52 remission was achieved by 3% on 
placebo and 10% on adalimumab. 
 
Patients from studies UC-I and UC-II had the option to roll over into an open-label long-term extension 
study (UC III). Following 3 years of adalimumab therapy, 75% (301/402) continued to be in clinical 
remission per partial Mayo score.  
 
Hospitalisation rates 
 
During 52 weeks of studies UC-I and UC-II, lower rates of all-cause hospitalisations and UC-related 
hospitalisations were observed for the adalimumab-treated arm compared to the placebo arm. The number 
of all cause hospitalisations in the adalimumab treatment group was 0.18 per patient year vs. 0.26 per 



197 

patient year in the placebo group and the corresponding figures for UC-related hospitalisations were 0.12 
per patient year vs. 0.22 per patient year. 
 
Quality of life 
 
In study UC-II, treatment with adalimumab resulted in improvements in the Inflammatory Bowel Disease 
Questionnaire (IBDQ) score.  
 
Uveitis 
 
The safety and efficacy of Humira were assessed in adult patients with non-infectious intermediate, 
posterior, and panuveitis, excluding patients with isolated anterior uveitis, in two randomised, double-
masked, placebo-controlled studies (UV I and II). Patients received placebo or Humira at an initial dose of 
80 mg followed by 40 mg every other week starting one week after the initial dose. Concomitant stable 
doses of one non-biologic immunosuppressant were permitted.  
 
Study UV I evaluated 217 patients with active uveitis despite treatment with corticosteroids (oral 
prednisone at a dose of 10 to 60 mg/day). All patients received a 2-week standardised dose of prednisone 
60 mg/day at study entry followed by a mandatory taper schedule, with complete corticosteroid 
discontinuation by Week 15.  
 
Study UV II evaluated 226 patients with inactive uveitis requiring chronic corticosteroid treatment (oral 
prednisone 10 to 35 mg/day) at baseline to control their disease. Patients subsequently underwent a 
mandatory taper schedule, with complete corticosteroid discontinuation by Week 19.  
 
The primary efficacy endpoint in both studies was ´time to treatment failure´. Treatment failure was 
defined by a multi-component outcome based on inflammatory chorioretinal and/or inflammatory retinal 
vascular lesions, anterior chamber (AC) cell grade, vitreous haze (VH) grade and best corrected visual 
acuity (BCVA).  
 
Patients who completed Studies UV I and UV II were eligible to enroll in an uncontrolled long-term 
extension study with an originally planned duration of 78 weeks. Patients were allowed to continue on 
study medication beyond Week 78 until they had access to Humira. 
 
Clinical Response 
 
Results from both studies demonstrated statistically significant reduction of the risk of treatment failure in 
patients treated with Humira versus patients receiving placebo (See Table 24). Both studies demonstrated 
an early and sustained effect of Humira on the treatment failure rate versus placebo (see Figure 2).  
 



198 

Table 24 
Time to Treatment Failure in Studies UV I and UV II 

 
Analysis 
 Treatment 

N Failure 
N (%) 

Median Time to 
Failure (months) 

HRa CI 95% 
for HRa 

P Value b 

Time to Treatment Failure At or After Week 6 in Study UV I   
Primary analysis (ITT)   
 Placebo 107 84 (78.5) 3.0 -- -- -- 
 Adalimumab 110 60 (54.5) 5.6 0.50 0.36, 0.70  < 0.001
Time to Treatment Failure At or After Week 2 in Study UV II 
Primary analysis (ITT)   
 Placebo 111 61 (55.0) 8.3 -- -- -- 
 Adalimumab 115 45 (39.1) NEc 0.57 0.39, 0.84 0.004 

Note:  Treatment failure at or after Week 6 (Study UV I), or at or after Week 2 (Study UV II), was 
counted as event. Drop outs due to reasons other than treatment failure were censored at the time of 
dropping out. 
a HR of adalimumab vs placebo from proportional hazards regression with treatment as factor. 
b 2-sided P value from log rank test. 
c NE = not estimable. Fewer than half of at-risk subjects had an event.  
 
Figure 2: Kaplan-Meier Curves Summarizing Time to Treatment Failure on or after Week 6 (Study 

UV I) or Week 2 (Study UV II) 
 

T
R

E
A

T
M

E
N

T
 F

A
IL

U
R

E
 R

A
T

E
 (

%
) 

 TIME (MONTHS) 
 Study UV I                        Treatment Placebo Adalimumab 



199 

T
R

E
A

T
M

E
N

T
 F

A
IL

U
R

E
 R

A
T

E
 (

%
) 

 TIME (MONTHS)
 Study UV II                       Treatment Placebo Adalimumab 

Note: P# = Placebo (Number of Events/Number at Risk); A# = HUMIRA (Number of 
Events/Number at Risk). 

 
In Study UV I statistically significant differences in favour of adalimumab versus placebo were observed 
for each component of treatment failure.  In Study UV II, statistically significant differences were 
observed for visual acuity only, but the other components were numerically in favour of adalimumab. 
 
Of the 424 subjects included in the uncontrolled long-term extension of Studies UV I and UV II, 60 
subjects were regarded ineligible (e.g. due to deviations or due to complications secondary to diabetic 
retinopathy, due to cataract surgery or vitrectomy) and were excluded from the primary analysis of 
efficacy. Of the 364 remaining patients, 269 evaluable patients (74%) reached 78 weeks of open-label 
adalimumab treatment. Based on the observed data approach, 216 (80.3%) were in quiescence (no active 
inflammatory lesions, AC cell grade  ≤ 0.5+, VH grade ≤ 0.5+) with a concomitant steroid dose ≤ 7.5 mg 
per day, and 178 (66.2%) were in steroid-free quiescence. BCVA was either improved or maintained (< 5 
letters deterioration) in 88.6% of the eyes at week 78. Data beyond Week 78 were generally consistent 
with these results but the number of enrolled subjects declined after this time. Overall, among the patients 
who discontinued the study, 18% discontinued due to adverse events, and 8% due to insufficient response 
to adalimumab treatment. 
 
Quality of Life 
 
Patient reported outcomes regarding vision-related functioning were measured in both clinical studies, 
using the NEI VFQ-25. Humira was numerically favoured for the majority of subscores with statistically 
significant mean differences for general vision, ocular pain, near vision, mental health, and total score in 
Study UV I, and for general vision and mental health in Study UV II. Vision related effects were not 
numerically in favour of Humira for colour vision in Study UVI and for colour vision, peripheral vision 
and near vision in Study UV II. 
 
Immunogenicity 
 
Formation of anti-adalimumab antibodies is associated with increased clearance and reduced efficacy of 
adalimumab. There is no apparent correlation between the presence of anti-adalimumab antibodies and the 
occurrence of adverse events. 
 



200 

Patients in rheumatoid arthritis studies I, II and III were tested at multiple time points for anti-adalimumab 
antibodies during the 6 to 12 month period. In the pivotal trials, anti-adalimumab antibodies were 
identified in 5.5% (58/1053) of patients treated with adalimumab, compared to 0.5% (2/370) on placebo.  
In patients not given concomitant methotrexate, the incidence was 12.4%, compared to 0.6% when 
adalimumab was used as add-on to methotrexate.   
 
In patients with polyarticular juvenile idiopathic arthritis who were 4 to 17 years, anti-adalimumab 
antibodies were identified in 15.8% (27/171) of patients treated with adalimumab. In patients not given 
concomitant methotrexate, the incidence was 25.6% (22/86) compared to 5.9% (5/85) when adalimumab 
was used as add-on to methotrexate. In patients with polyarticular juvenile idiopathic arthritis who were 
2 to <4 years old or aged 4 and above weighing <15 kg, anti-adalimumab antibodies were identified in 7% 
(1/15) of patients, and the one patient was receiving concomitant methotrexate. 
 
In patients with enthesitis-related arthritis, anti-adalimumab antibodies were identified in 10.9% (5/46) of 
patients treated with adalimumab. In patients not given concomitant methotrexate, the incidence was 
13.6% (3/22), compared to 8.3% (2/24) when adalimumab was used as add-on to methotrexate. 
 
In patients with psoriatic arthritis, anti-adalimumab antibodies were identified in 38/376 subjects (10%) 
treated with adalimumab. In patients not given concomitant methotrexate, the incidence was 13.5% 
(24/178 subjects), compared to 7% (14 of 198 subjects) when adalimumab was used as add-on to 
methotrexate. 
 
In patients with ankylosing spondylitis anti-adalimumab antibodies were identified in 17/204 subjects 
(8.3%) treated with adalimumab. In patients not given concomitant methotrexate, the incidence was 
16/185 (8.6%), compared to 1/19 (5.3%) when adalimumab was used as add-on to methotrexate. 
 
In patients with non-radiographic axial spondyloarthritis, anti-adalimumab antibodies were identified in 
8/152 subjects (5.3%) who were treated continuously with adalimumab. 
 
In patients with Crohn’s disease, anti-adalimumab antibodies were identified in 7/269 subjects (2.6%) and 
in 19/487 subjects (3.9%) with ulcerative colitis. 
 
In adult patients with psoriasis, anti-adalimumab antibodies were identified in 77/920 subjects (8.4%) 
treated with adalimumab monotherapy. 
 
In adult plaque psoriasis patients on long term adalimumab monotherapy who participated in a withdrawal 
and retreatment study, the rate of antibodies to adalimumab after retreatment (11 of 482 subjects, 2.3%) 
was similar to the rate observed prior to withdrawal (11 of 590 subjects, 1.9%). 
 
In patients with paediatric psoriasis, anti-adalimumab antibodies were identified in 5/38 subjects (13%) 
treated with 0.8 mg/kg adalimumab monotherapy. 
 
In patients with moderate to severe hidradenitis suppurativa, anti-adalimumab antibodies were identified 
in 10/99 subjects (10.1%) treated with adalimumab. 
 
In patients with moderately to severely active paediatric Crohn’s disease, the rate of anti-adalimumab 
antibody development in patients receiving adalimumab was 3.3%.  
 
In adult patients with non-infectious uveitis, anti-adalimumab antibodies were identified in 4.8% (12/249) 
of patients treated with adalimumab. 
 
In patients with moderately to severely active paediatric ulcerative colitis, the rate of anti-adalimumab 
antibody development in patients receiving adalimumab was 3%. 



201 

 
Because immunogenicity analyses are product-specific, comparison of antibody rates with those from 
other products is not appropriate. 
 
Paediatric population 
 
Juvenile idiopathic arthritis (JIA) 
 
Polyarticular juvenile idiopathic arthritis (pJIA) 
 
The safety and efficacy of Humira was assessed in two studies (pJIA I and II) in children with active 
polyarticular or polyarticular course juvenile idiopathic arthritis, who had a variety of JIA onset types 
(most frequently rheumatoid-factor negative or positive polyarthritis and extended oligoarthritis). 
 
pJIA I 
 

The safety and efficacy of Humira were assessed in a multicentre, randomised, double-blind, 
parallel − group study in 171 children (4-17 years old) with polyarticular JIA. In the open-label lead in 
phase (OL LI) patients were stratified into two groups, MTX (methotrexate)-treated or non-MTX-treated. 
Patients who were in the non-MTX stratum were either naïve to or had been withdrawn from MTX at 
least two weeks prior to study drug administration. Patients remained on stable doses of NSAIDs and or 
prednisone ( 0.2 mg/kg/day or 10 mg/day maximum). In the OL LI phase all patients received 24 mg/m2 

up to a maximum of 40 mg Humira every other week for 16 weeks.  The distribution of patients by age 
and minimum, median and maximum dose received during the OL LI phase is presented in Table 25. 
 

Table 25  
Distribution of patients by age and adalimumab dose received during the OL LI phase 

 
Age Group Number of patients at Baseline 

n (%) 
Minimum, median and maximum 
dose

4 to 7 years 31 (18.1) 10, 20 and 25 mg 

8 to 12 years 71 (41.5) 20, 25 and 40 mg 
13 to 17 years 69 (40.4) 25, 40 and 40 mg 

 
Patients demonstrating a Paediatric ACR 30 response at Week 16 were eligible to be randomised into the 
double blind (DB) phase and received either Humira 24 mg/m2 up to a maximum of 40 mg, or placebo 
every other week for an additional 32 weeks or until disease flare. Disease flare criteria were defined as a 
worsening of  30% from baseline in  3 of 6 Paediatric ACR core criteria,  2 active joints, and 
improvement of  30% in no more than 1 of the 6 criteria. After 32 weeks or at disease flare, patients 
were eligible to enrol into the open label extension phase.  
 



202 

Table 26 
Ped ACR 30 Responses in the JIA study 

 
Stratum MTX Without MTX 
Phase  
OL-LI 16 weeks  

Ped ACR 30 
response (n/N) 

94.1% (80/85) 74.4% (64/86) 

                                                           Efficacy Outcomes
Double Blind 32 weeks Humira /MTX 

(N = 38) 
 

Placebo / MTX 
(N = 37) 

Humira  
(N = 30) 

Placebo 
(N = 28) 

Disease flares at 
the end of 
32 weeksa (n/N)

36.8% (14/38) 64.9% (24/37)b 43.3% (13/30) 71.4% 
(20/28)c 

Median time to 
disease flare 

>32 weeks 20 weeks >32 weeks 14 weeks 

 

a Ped ACR 30/50/70 responses Week 48 significantly greater than those of placebo treated patients  
b p = 0.015 
c p = 0.031 
 

Amongst those who responded at Week 16 (n=144), the Paediatric ACR 30/50/70/90 responses were 
maintained for up to six years in the OLE phase in patients who received Humira throughout the study. 
Over all 19 subjects, of which 11 of the baseline age group 4 to 12 and 8 of the baseline age group 13 to 
17 years were treated 6 years or longer. 
 
Overall responses were generally better and, fewer patients developed antibodies when treated with the 
combination of Humira and MTX compared to Humira alone. Taking these results into consideration, 
Humira is recommended for use in combination with MTX and for use as monotherapy in patients for 
whom MTX use is not appropriate (see section 4.2). 
 
pJIA II 
 
The safety and efficacy of Humira was assessed in an open-label, multicentre study in 32 children 
(2 - < 4 years old or aged 4 and above weighing < 15 kg) with moderately to severely active polyarticular 
JIA. The patients received 24 mg/m2 body surface area (BSA) of Humira up to a maximum of 20 mg 
every other week as a single dose via SC injection for at least 24 weeks. During the study, most subjects 
used concomitant MTX, with fewer reporting use of corticosteroids or NSAIDs. 
 
At Week 12 and Week 24, PedACR30 response was 93.5% and 90.0%, respectively, using the observed 
data approach. The proportions of subjects with PedACR50/70/90 at Week 12 and Week 24 were 
90.3%/61.3%/38.7% and 83.3%/73.3%/36.7%, respectively. Amongst those who responded (Paediatric 
ACR 30) at Week 24 (n=27 out of 30 patients), the Paediatric ACR 30 responses were maintained for up 
to 60 weeks in the OLE phase in patients who received Humira throughout this time period. Overall, 
20 subjects were treated for 60 weeks or longer. 
 
Enthesitis-related arthritis 
 
The safety and efficacy of Humira were assessed in a multicentre, randomised, double-blind study in 46 
paediatric patients (6 to 17 years old) with moderate enthesitis-related arthritis. Patients were randomised 
to receive either 24 mg/m2 body surface area (BSA) of Humira up to a maximum of 40 mg, or placebo 
every other week for 12 weeks. The double-blind period is followed by an open-label (OL) period during 



203 

which patients received 24 mg/m2 BSA of Humira up to a maximum of 40 mg every other week 
subcutaneously for up to an additional 192 weeks. The primary endpoint was the percent change from 
Baseline to Week 12 in the number of active joints with arthritis (swelling not due to deformity or joints 
with loss of motion plus pain and/or tenderness), which was achieved with mean percent decrease of -
62.6% (median percent change -88.9%) in patients in the Humira group compared to -11.6% (median 
percent change -50.0%) in patients in the placebo group. Improvement in number of active joints with 
arthritis was maintained during the OL period through Week 156 for the 26 of 31 (84%) patients in the 
Humira group who remained in the study. Although not statistically significant, the majority of patients 
demonstrated clinical improvement in secondary endpoints such as number of sites of enthesitis, tender 
joint count (TJC), swollen joint count (SJC), Paediatric ACR 50 response, and Paediatric ACR 70 
response. 
 
Paediatric plaque psoriasis  
 
The efficacy of Humira was assessed in a randomised, double-blind, controlled study of 114 paediatric 
patients from 4 years of age with severe chronic plaque psoriasis (as defined by a PGA ≥ 4 or > 20% BSA 
involvement or > 10% BSA involvement with very thick lesions or PASI ≥ 20 or ≥ 10 with clinically 
relevant facial, genital, or hand/ foot involvement) who were inadequately controlled with topical therapy 
and heliotherapy or phototherapy.  
 
Patients received Humira 0.8 mg/kg eow (up to 40 mg), 0.4 mg/kg eow (up to 20 mg), or methotrexate 
0.1- 0.4 mg/kg weekly (up to 25 mg).   At Week 16, more patients randomised to Humira 0.8 mg/kg had 
positive efficacy responses (e.g., PASI 75) than those randomised to 0.4 mg/kg eow or MTX.   
 

Table 27:  Paediatric Plaque Psoriasis Efficacy Results at 16 Weeks 

 
MTXa 
N=37 

Humira 0.8 mg/kg eow 
N=38  

 PASI 75b 12 (32.4%) 22 (57.9%) 
 PGA: Clear/minimalc 15 (40.5%) 23 (60.5%) 
a MTX = methotrexate 
b P=0.027, Humira 0.8 mg/kg versus MTX 
c P=0.083, Humira 0.8 mg/kg versus MTX

 
Patients who achieved PASI 75 and PGA clear or minimal were withdrawn from treatment for up to 
36 weeks and monitored for loss of disease control (i.e. a worsening of PGA by at least 2 grades).  Patients 
were then re-treated with adalimumab 0.8 mg/kg eow for an additional 16 weeks and response rates 
observed during retreatment were similar to the previous double-blind period:  PASI 75 response of 78.9% 
(15 of 19 subjects) and PGA clear or minimal of 52.6% (10 of 19 subjects). 
 
In the open label period of the study, PASI 75 and PGA clear or minimal responses were maintained for 
up to an additional 52 weeks with no new safety findings. 
 
Adolescent hidradenitis suppurativa 
 
There are no clinical trials with Humira in adolescent patients with HS.  Efficacy of adalimumab for the 
treatment of adolescent patients with HS is predicted based on the demonstrated efficacy and exposure-
response relationship in adult HS patients and the likelihood that the disease course, pathophysiology, and 
drug effects are substantially similar to that of adults at the same exposure levels. Safety of the 
recommended adalimumab dose in the adolescent HS population is based on cross-indication safety 
profile of adalimumab in both adults and paediatric patients at similar or more frequent doses (see section 
5.2). 
 



204 

Paediatric Crohn’s disease  
 

Humira was assessed in a multicentre, randomised, double-blind clinical trial designed to evaluate the 
efficacy and safety of induction and maintenance treatment with doses dependent on body weight (< 40 kg 
or ≥ 40 kg) in 192 paediatric subjects between the ages of 6 and 17 (inclusive) years, with moderate to 
severe Crohn´s disease (CD) defined as Paediatric Crohn's Disease Activity Index (PCDAI) score > 30.  
Subjects had to have failed conventional therapy (including a corticosteroid and/or an immunomodulator) 
for CD. Subjects may also have previously lost response or been intolerant to infliximab.  
 
All subjects received open-label induction therapy at a dose based on their Baseline body weight: 160 mg 
at Week 0 and 80 mg at Week 2 for subjects ≥ 40 kg, and 80 mg and 40 mg, respectively, for subjects 
< 40 kg. 
 
At Week 4, subjects were randomised 1:1 based on their body weight at the time to either the Low Dose or 
Standard Dose maintenance regimens as shown in Table 28. 
 

Table 28 
Maintenance regimen

Patient 
Weight 

Low dose Standard 
dose 

< 40 kg 10 mg eow 20 mg eow
≥ 40 kg 20 mg eow 40 mg eow

 
Efficacy results 
 
The primary endpoint of the study was clinical remission at Week 26, defined as PCDAI score  10. 
 
Clinical remission and clinical response (defined as reduction in PCDAI score of at least 15 points from 
Baseline) rates are presented in Table 29. Rates of discontinuation of corticosteroids or 
immunomodulators are presented in Table 30. 
 

Table 29 
Paediatric CD Study 

PCDAI Clinical Remission and Response 
 Standard Dose

40/20 mg eow 
N = 93 

Low Dose 
20/10 mg eow 

N = 95 

P value* 

Week 26    
   Clinical remission 38.7% 28.4% 0.075 
   Clinical response  59.1% 48.4% 0.073 
Week 52    
   Clinical remission 33.3% 23.2% 0.100 
   Clinical response 41.9% 28.4% 0.038 
* p value for Standard Dose versus Low Dose comparison.

 



205 

Table 30 
Paediatric CD Study 

Discontinuation of Corticosteroids or Immunomodulators and Fistula Remission 
 Standard Dose

40/20 mg eow  
Low Dose 

20/10 mg eow  
P value1 

Discontinued corticosteroids N= 33 N=38  
Week 26 84.8% 65.8% 0.066 
Week 52 69.7% 60.5% 0.420 
Discontinuation of Immunomodulators2 N=60 N=57  
Week 52 30.0% 29.8% 0.983 
Fistula remission3 N=15 N=21  
Week 26 46.7% 38.1% 0.608 
Week 52 40.0% 23.8% 0.303 
1  p value for Standard Dose versus Low Dose comparison. 
2  Immunosuppressant therapy could only be discontinued at or after Week 26 at the 
investigator's discretion if the subject met the clinical response criterion  
3 defined as a closure of all fistulas that were draining at Baseline for at least 2 consecutive 
post-Baseline visits

 
Statistically significant increases (improvement) from Baseline to Week 26 and 52 in Body Mass Index 
and height velocity were observed for both treatment groups. 
 
Statistically and clinically significant improvements from Baseline were also observed in both treatment 
groups for quality of life parameters (including IMPACT III). 
 
One hundred patients (n=100) from the Paediatric CD Study continued in an open-label long-term 
extension study.  After 5 years of adalimumab therapy, 74.0% (37/50) of the 50 patients remaining in the 
study continued to be in clinical remission, and 92.0% (46/50) of patients continued to be in clinical 
response per PCDAI. 
 
Paediatric ulcerative colitis 
 
The safety and efficacy of Humira was assessed in a multicenter, randomized, double-blind, trial in 93 
paediatric patients from 5 to 17 years of age with moderate to severe ulcerative colitis (Mayo score 6 to 12 
with endoscopy subscore of 2 to 3 points, confirmed by centrally read endoscopy) who had an inadequate 
response or intolerance to conventional therapy. Approximately 16% of patients in the study had failed 
prior anti-TNF treatment. Patients who received corticosteroids at enrollment were allowed to taper their 
corticosteroid therapy after Week 4. 
 
In the induction period of the study, 77 patients were randomized 3:2 to receive double-blind treatment 
with Humira at an induction dose of 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2; or an induction dose of 2.4 mg/kg (maximum of 160 mg) at Week 
0, placebo at Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2. Both groups received 0.6 mg/kg 
(maximum of 40 mg) at Week 4 and Week 6. Following an amendment to the study design, the remaining 
16 patients who enrolled in the induction period received open-label treatment with Humira at the 
induction dose of 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 mg/kg (maximum of 
80 mg) at Week 2.  
 
At Week 8, 62 patients who demonstrated clinical response per Partial Mayo Score (PMS; defined as a 
decrease in PMS ≥ 2 points and ≥ 30% from Baseline) were randomized equally to receive double-blind 
maintenance treatment with Humira at a dose of 0.6 mg/kg (maximum of 40 mg) every week (ew), or a 
maintenance dose of 0.6 mg/kg (maximum of 40 mg) every other week (eow). Prior to an amendment to 



206 

the study design, 12 additional patients who demonstrated clinical response per PMS were randomized to 
receive placebo but were not included in the confirmatory analysis of efficacy. 
 
Disease flare was defined as an increase in PMS of at least 3 points (for patients with PMS of 0 to 2 at 
Week 8), at least 2 points (for patients with PMS of 3 to 4 at Week 8), or at least 1 point (for patients with 
PMS of 5 to 6 at Week 8).  
 
Patients who met criteria for disease flare at or after Week 12 were randomized to receive a re-induction 
dose of 2.4 mg/kg (maximum of 160 mg) or a dose of 0.6 mg/kg (maximum of 40 mg) and continued to 
receive their respective maintenance dose regimen afterwards.  
 

Efficacy Results 

 

The co-primary endpoints of the study were clinical remission per PMS (defined as PMS ≤ 2 and no 
individual subscore > 1) at Week 8, and clinical remission per FMS (Full Mayo Score) (defined as a Mayo 
Score ≤ 2 and no individual subscore > 1) at Week 52 in patients who achieved clinical response per PMS 
at Week 8. 
 
Clinical remission rates per PMS at Week 8 for patients in each of the Humira double-
blind induction groups are presented in Table 31.  

Table 31: Clinical Remission per PMS at 8 Weeks  

 

Humiraa 
Maximum of 160 mg at Week 

0 / Placebo at Week 1  
N=30 

Humirab, c  
Maximum of 160 mg at Week 

0 and Week 1  
N=47 

Clinical remission 13/30 (43.3%) 28/47 (59.6%) 

a Humira 2.4 mg/kg (maximum of 160 mg) at Week 0, placebo at Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2  
b Humira 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2  
c Not including open-label Induction dose of Humira 2.4 mg/kg (maximum of 160 mg) at 
Week 0 and Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2 
Note 1: Both induction groups received 0.6 mg/kg (maximum of 40 mg) at Week 4 and 
Week 6  
Note 2: Patients with missing values at Week 8 were considered as not having met the 
endpoint  

 
At Week 52, clinical remission per FMS in Week 8 responders, clinical response per FMS (defined as a 
decrease in Mayo Score ≥ 3 points and ≥ 30% from Baseline) in Week 8 responders, mucosal healing per 
FMS (defined as an Mayo endoscopy score ≤ 1) in Week 8 responders, clinical remission per FMS in 
Week 8 remitters, and the proportion of subjects in corticosteroid-free remission per FMS in Week 8 
responders were assessed in patients who received Humira at the double-blind maximum 40 mg eow (0.6 
mg/kg) and maximum 40 mg ew (0.6 mg/kg) maintenance doses (Table 32). 

 



207 

Table 32: Efficacy Results at 52 Weeks  

Humiraa   
Maximum of 40 mg eow 

N=31 

Humirab   
Maximum of 40 mg ew  

N=31 

Clinical remission in Week 
8 PMS responders  

9/31 (29.0%)  14/31 (45.2%) 

Clinical response in Week 8 
PMS responders  

19/31 (61.3%)  21/31 (67.7%)  

Mucosal healing in 
Week 8 PMS responders  

12/31 (38.7%)  16/31 (51.6%)  

Clinical remission in Week 
8 PMS remitters  

9/21 (42.9%)  10/22 (45.5%)  

Corticosteroid-free 
remission in Week 8 
PMS respondersc  

4/13 (30.8%)  5/16 (31.3%)  

a Humira 0.6 mg/kg (maximum of 40 mg) every other week  
b Humira 0.6 mg/kg (maximum of 40 mg) every week  
c In patients receiving concomitant corticosteroids at baseline  
Note: Patients with missing values at Week 52 or who were randomized to receive 
re-induction or maintenance treatment were considered non-responders for Week 52 
endpoints  

 
Additional exploratory efficacy endpoints included clinical response per the Paediatric Ulcerative Colitis 
Activity Index (PUCAI) (defined as a decrease in PUCAI ≥ 20 points from Baseline) and clinical 
remission per PUCAI (defined as PUCAI < 10) at Week 8 and Week 52 (Table 33).  
 



208 

Table 33: Exploratory Endpoints Results per PUCAI 
 Week 8 

Humiraa

Maximum of 160 mg at 
Week 0 / Placebo at Week 1 

N=30 

Humirab,c 

Maximum of 160 mg at 
Week 0 and Week 1 

N=47 
Clinical remission per PUCAI 10/30 (33.3%) 22/47 (46.8%) 
Clinical response per PUCAI 15/30 (50.0%) 32/47 (68.1%) 
 Week 52 

Humirad

Maximum of 40 mg eow 
N=31

Humirae 

Maximum of 40 mg ew 
N=31 

Clinical remission per PUCAI 
in Week 8 PMS responders 

14/31 (45.2%) 18/31 (58.1%) 

Clinical response per PUCAI 
in Week 8 PMS responders 

18/31 (58.1%) 16/31 (51.6%) 

a Humira 2.4 mg/kg (maximum of 160 mg) at Week 0, placebo at Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2  
b  Humira 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2  
c Not including open-label Induction dose of Humira 2.4 mg/kg (maximum of 160 mg) at 
Week 0 and Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2 
d Humira 0.6 mg/kg (maximum of 40 mg) every other week 
e Humira 0.6 mg/kg (maximum of 40 mg) every week 
Note 1: Both induction groups received 0.6 mg/kg (maximum of 40 mg) at Week 4 and 
Week 6  
Note 2: Patients with missing values at Week 8 were considered as not having met the 
endpoints  
Note 3: Patients with missing values at Week 52 or who were randomized to receive re-
induction or maintenance treatment were considered non-responders for Week 52 
endpoints 

 
Of the Humira-treated patients who received re-induction treatment during the maintenance period, 2/6 
(33%) achieved clinical response per FMS at Week 52. 
 
Quality of life 
 
Clinically meaningful improvements from Baseline were observed in IMPACT III and the caregiver Work 
Productivity and Activity Impairment (WPAI) scores for the groups treated with Humira.  
 
Clinically meaningful increases (improvement) from Baseline in height velocity were observed for the 
groups treated with adalimumab, and clinically meaningful increases (improvement) from Baseline in 
Body Mass Index were observed for subjects on the high maintenance dose of maximum 40 mg (0.6 
mg/kg) ew.  
 
Paediatric Uveitis  
 
The safety and efficacy of Humira was assessed in a randomized, double-masked, controlled study of 90 
paediatric patients from 2 to < 18 years of age with active JIA-associated noninfectious anterior uveitis 
who were refractory to at least 12 weeks of methotrexate treatment.  Patients received either placebo or 
20 mg adalimumab (if < 30 kg) or 40 mg adalimumab (if ≥ 30 kg) every other week in combination with 
their baseline dose of methotrexate.  



209 

 
The primary endpoint was ‘time to treatment failure’. The criteria determining treatment failure were 
worsening or sustained non-improvement in ocular inflammation, partial improvement with development 
of sustained ocular co-morbidities or worsening of ocular co-morbidities, non-permitted use of 
concomitant medications, and suspension of treatment for an extended period of time. 
 
Clinical Response 
 
Adalimumab significantly delayed the time to treatment failure, as compared to placebo (See Figure 3, 
P < 0.0001 from log rank test).The median time to treatment failure was 24.1 weeks for subjects treated 
with placebo, whereas the median time to treatment failure was not estimable for subjects treated with 
adalimumab because less than one-half of these subjects experienced treatment failure.  Adalimumab 
significantly decreased the risk of treatment failure by 75% relative to placebo, as shown by the hazard 
ratio (HR = 0.25 [95% CI:  0.12, 0.49]). 
 

Figure 3: Kaplan-Meier Curves Summarizing Time to Treatment Failure in the Paediatric Uveitis 

Study 

 

P
R

O
B

A
B

IL
IT

Y
 O

F
 F

A
IL

IN
G

 T
R

E
A

T
M

E
N

T
 

 TIME (WEEKS) 
 Treatment Placebo  Adalimumab 
 Note: P = Placebo (Number at Risk); H = HUMIRA (Number at Risk).

 
 
5.2 Pharmacokinetic properties 



210 

 
Absorption and distribution 
 
After subcutaneous administration of a single 40 mg dose, absorption and distribution of adalimumab was 
slow, with peak serum concentrations being reached about 5 days after administration. The average 
absolute bioavailability of adalimumab estimated from three studies following a single 40 mg 
subcutaneous dose was 64%. After single intravenous doses ranging from 0.25 to 10 mg/kg, 
concentrations were dose proportional. After doses of 0.5 mg/kg (~40 mg), clearances ranged from 11 to 
15 ml/hour, the distribution volume (Vss) ranged from 5 to 6 litres and the mean terminal phase half-life 
was approximately two weeks. Adalimumab concentrations in the synovial fluid from several rheumatoid 
arthritis patients ranged from 31-96% of those in serum. 
 
Following subcutaneous administration of 40 mg of adalimumab every other week in adult rheumatoid 
arthritis (RA) patients the mean steady-state trough concentrations were approximately 5 g/ml (without 
concomitant methotrexate) and 8 to 9 g/ml (with concomitant methotrexate), respectively.  The serum 
adalimumab trough levels at steady-state increased roughly proportionally with dose following 20, 40 and 
80 mg subcutaneous dosing every other week and every week. 
 
Following the administration of 24 mg/m2 (maximum of 40 mg) subcutaneously every other week to 
patients with polyarticular juvenile idiopathic arthritis (JIA) who were 4 to 17 years the mean trough 
steady-state (values measured from Week 20 to 48) serum adalimumab concentration was 5.6 ± 5.6 µg/ml 
(102% CV) for adalimumab without concomitant methotrexate and 10.9 ± 5.2 µg/ml (47.7% CV) with 
concomitant methotrexate. 
 
In patients with polyarticular JIA who were 2 to < 4 years old or aged 4 and above weighing < 15 kg 
dosed with adalimumab 24 mg/m2 , the mean trough steady-state serum adalimumab concentrations was 
6.0  ±  6.1 µg/ml (101% CV) for adalimumab without concomitant methotrexate and 7.9 ± 5.6 µg/ml 
(71.2% CV) with concomitant methotrexate. 
 
Following the administration of 24 mg/m2 (maximum of 40 mg) subcutaneously every other week to 
patients with enthesitis-related arthritis who were 6 to 17 years, the mean trough steady-state (values 
measured at Week 24) serum adalimumab concentrations were 8.8 ± 6.6 μg/ml for adalimumab without 
concomitant methotrexate and 11.8 ± 4.3 μg/ml with concomitant methotrexate. 
 
Following subcutaneous administration of 40 mg of adalimumab every other week in adult non-
radiographic axial spondyloarthritis patients, the mean (±SD) trough steady-state concentration at 
Week 68 was 8.0 ± 4.6 g/ml. 
 
In adult patients with psoriasis, the mean steady-state trough concentration was 5 g/ml during 
adalimumab 40 mg every other week monotherapy treatment. 
 
Following the administration of 0.8 mg/kg (maximum of 40 mg) subcutaneously every other week to 
paediatric patients with chronic plaque psoriasis, the mean ± SD steady-state adalimumab trough 
concentration was approximately 7.4 ± 5.8 µg/ml (79% CV). 
 
In adult patients with hidradenitis suppurativa, a dose of 160 mg Humira on Week 0 followed by 80 mg on 
Week 2 achieved serum adalimumab trough concentrations of approximately 7 to 8 μg/ml at Week 2 and 
Week 4.  The mean steady-state trough concentration at Week 12 through Week 36 were approximately 8 
to 10 μg/ml during adalimumab 40 mg every week treatment.   
 
Adalimumab exposure in adolescent HS patients was predicted using population pharmacokinetic 
modelling and simulation based on cross-indication pharmacokinetics in other paediatric patients 
(paediatric psoriasis, juvenile idiopathic arthritis, paediatric Crohn’s disease, and enthesitis-related 



211 

arthritis). The recommended adolescent HS dosing schedule is 40 mg every other week. Since exposure to 
adalimumab can be affected by body size, adolescents with higher body weight and inadequate response 
may benefit from receiving the recommended adult dose of 40 mg every week. 
 
In patients with Crohn’s disease, the loading dose of 80 mg Humira on Week 0 followed by 40 mg Humira 
on Week 2 achieves serum adalimumab trough concentrations of approximately 5.5 g/ml during the 
induction period. A loading dose of 160 mg Humira on Week 0 followed by 80 mg Humira on Week 2 
achieves serum adalimumab trough concentrations of approximately 12 g/ml during the induction period. 
Mean steady-state trough levels of approximately 7 g/ml were observed in Crohn’s disease patients who 
received a maintenance dose of 40 mg Humira every other week. 
 
In paediatric patients with moderate to severe CD, the open-label adalimumab induction dose was 
160/80 mg or 80/40 mg at Weeks 0 and 2, respectively, dependent on a body weight cut-off of 40 kg.  At 
Week 4, patients were randomised 1:1 to either the Standard Dose (40/20 mg eow) or Low Dose 
(20/10 mg eow) maintenance treatment groups based on their body weight. The mean (±SD) serum 
adalimumab trough concentrations achieved at Week 4 were 15.7 ± 6.6 g/ml for patients ≥ 40 kg 
(160/80 mg) and 10.6 ± 6.1 g/ml for patients < 40 kg (80/40 mg).  
 
For patients who stayed on their randomised therapy, the mean (±SD) adalimumab trough concentrations 
at Week 52 were 9.5 ± 5.6 g/ml for the Standard Dose group and 3.5 ± 2.2 g/ml for the Low Dose 
group.  The mean trough concentrations were maintained in patients who continued to receive adalimumab 
treatment eow for 52 weeks. For patients who dose escalated from eow to weekly regimen, the mean 
(±SD) serum concentrations of adalimumab at Week 52 were 15.3 ± 11.4 μg/ml (40/20 mg, weekly) and 
6.7 ± 3.5 μg/ml (20/10 mg, weekly). 
 
In patients with ulcerative colitis, a loading dose of 160 mg Humira on Week 0 followed by 80 mg Humira 
on Week 2 achieves serum adalimumab trough concentrations of approximately 12 g/ml during the 
induction period.  Mean steady-state trough levels of approximately 8 g/ml were observed in ulcerative 
colitis patients who received a maintenance dose of 40 mg Humira every other week.  
 
Following the subcutaneous administration of body weight-based dosing of 0.6 mg/kg (maximum of 
40 mg) every other week to paediatric patients with ulcerative colitis, the mean trough steady-state serum 
adalimumab concentration was 5.01±3.28 µg/ml at Week 52. For patients who received 0.6 mg/kg 
(maximum of 40 mg) every week, the mean (±SD) trough steady-state serum adalimumab concentration 
was 15.7±5.60 μg/ml at Week 52.  
 
In adult patients with uveitis, a loading dose of 80 mg adalimumab on Week 0 followed by 40 mg 
adalimumab every other week starting at Week 1, resulted in mean steady-state concentrations of 
approximately 8 to 10 g/ml. 
 
Adalimumab exposure in paediatric uveitis patients was predicted using population pharmacokinetic 
modelling and simulation based on cross-indication pharmacokinetics in other paediatric patients 
(paediatric psoriasis, juvenile idiopathic arthritis, paediatric Crohn’s disease, and enthesitis-related 
arthritis). No clinical exposure data are available on the use of a loading dose in children < 6 years. The 
predicted exposures indicate that in the absence of methotrexate, a loading dose may lead to an initial 
increase in systemic exposure. 
 
Population pharmacokinetic and pharmacokinetic/pharmacodynamic modelling and simulation predicted 
comparable adalimumab exposure and efficacy in patients treated with 80 mg every other week when 
compared with 40 mg every week (including adult patients with RA, HS, UC, CD or Ps, patients with 
adolescent HS, and paediatric patients ≥ 40 kg with CD and UC). 
 
Exposure-response relationship in paediatric population 



212 

On the basis of clinical trial data in patients with JIA (pJIA and ERA), an exposure-response relationship 
was established between plasma concentrations and PedACR 50 response. The apparent adalimumab 
plasma concentration that produces half the maximum probability of PedACR 50 response (EC50) was 
3 μg/ml (95% CI: 1-6 μg/ml).  
 
Exposure-response relationships between adalimumab concentration and efficacy in paediatric patients 
with severe chronic plaque psoriasis were established for PASI 75 and PGA clear or minimal, 
respectively. PASI 75 and PGA clear or minimal increased with increasing adalimumab concentrations, 
both with a similar apparent EC50 of approximately 4.5 μg/ml (95% CI 0.4-47.6 and 1.9-10.5, 
respectively).   
 
Elimination 
 
Population pharmacokinetic analyses with data from over 1,300 RA patients revealed a trend toward 
higher apparent clearance of adalimumab with increasing body weight. After adjustment for weight 
differences, gender and age appeared to have a minimal effect on adalimumab clearance.  The serum 
levels of free adalimumab (not bound to anti-adalimumab antibodies, AAA) were observed to be lower in 
patients with measurable AAA. 
 
Hepatic or renal impairment 
 
Humira has not been studied in patients with hepatic or renal impairment. 
 
5.3 Preclinical safety data  
 
Non-clinical data reveal no special hazard for humans based on studies of single dose toxicity, repeated 
dose toxicity, and genotoxicity.   
 
An embryo-foetal developmental toxicity/perinatal developmental study has been performed in 
cynomolgus monkeys at 0, 30 and 100 mg/kg (9-17 monkeys/group) and has revealed no evidence of harm 
to the foetuses due to adalimumab. Neither carcinogenicity studies, nor a standard assessment of fertility 
and postnatal toxicity, were performed with adalimumab due to the lack of appropriate models for an 
antibody with limited cross-reactivity to rodent TNF and to the development of neutralising antibodies in 
rodents.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients  
 
Mannitol 
Polysorbate 80 
Water for injections 
 
6.2 Incompatibilities  
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life  
 
2 years 
 



213 

6.4 Special precautions for storage  
 
Store in a refrigerator (2C – 8C). Do not freeze. Keep the pre-filled syringe or pre-filled pen in its outer 
carton in order to protect from light.   
 
A single Humira pre-filled syringe or pre-filled pen may be stored at temperatures up to a maximum of 
25°C for a period of up to 14 days. The syringe or pen must be protected from light, and discarded if not 
used within the 14-day period. 
 
6.5 Nature and contents of container 
 
Humira 40 mg solution for injection in pre-filled syringe 
Humira 40 mg solution for injection in single-use pre-filled syringe (type I glass) with a plunger stopper 
(bromobutyl rubber) and a needle with a needle shield (thermoplastic elastomer).  
 
Packs of: 
 1 pre-filled syringe (0.4 ml sterile solution) with 1 alcohol pad in a blister. 
 2 pre-filled syringes (0.4 ml sterile solution), each with 1 alcohol pad, in a blister. 
 4 pre-filled syringes (0.4 ml sterile solution), each with 1 alcohol pad, in a blister. 
 6 pre-filled syringes (0.4 ml sterile solution), each with 1 alcohol pad, in a blister. 

 
Humira 40 mg solution for injection in pre-filled syringe with automatic needle guard 
Humira 40 mg solution for injection in single-use pre-filled syringe with automatic needle guard. The 
syringe is made from type I glass with a plunger stopper (bromobutyl rubber) and a needle with a needle 
shield (thermoplastic elastomer).  
 
Packs of: 
 1 pre-filled syringe with automatic needle guard (0.4 ml sterile solution) with 1 alcohol pad in a 

blister.  
 2 pre-filled syringes with automatic needle guard (0.4 ml sterile solution), each with 1 alcohol pad, 

in a blister.  
 6 pre-filled syringes with automatic needle guard (0.4 ml sterile solution), each with 1 alcohol pad, 

in a blister. 
 
Humira 40 mg solution for injection in pre-filled pen 
Humira 40 mg solution for injection in single-use pre-filled pen for patient use containing a pre-filled 
syringe. The syringe inside the pen is made from type 1 glass with a plunger stopper (bromobutyl rubber) 
and a needle with a needle shield (thermoplastic elastomer). 
 
Packs of: 

 1 pre-filled pen (0.4 ml sterile solution), with 2 alcohol pads in a blister. 
 2 pre-filled pens (0.4 ml sterile solution), each with 1 alcohol pad, in a blister. 
 4 pre-filled pens (0.4 ml sterile solution), each with 1 alcohol pad, in a blister. 
 6 pre-filled pens (0.4 ml sterile solution), each with 1 alcohol pad, in a blister. 

 
Not all presentations or pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 



214 

 
7. MARKETING AUTHORISATION HOLDER  
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
8. MARKETING AUTHORISATION NUMBERS  
 
Humira 40 mg solution for injection in pre-filled syringe 
EU/1/03/256/012 
EU/1/03/256/013 
EU/1/03/256/014 
EU/1/03/256/015 
 
Humira 40 mg solution for injection in pre-filled syringe with automatic needle guard 
EU/1/03/256/023 
EU/1/03/256/024 
EU/1/03/256/025 
 
Humira 40 mg solution for injection in pre-filled pen 
EU/1/03/256/016 
EU/1/03/256/017 
EU/1/03/256/018 
EU/1/03/256/019 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 08 September 2003 
Date of latest renewal: 08 September 2008  
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 



215 

1. NAME OF THE MEDICINAL PRODUCT  
 
Humira 80 mg solution for injection in pre-filled syringe 
Humira 80 mg solution for injection in pre-filled pen 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION  
 
Humira 80 mg solution for injection in pre-filled syringe  
Each 0.8 ml single dose pre-filled syringe contains 80 mg of adalimumab.  
 
Humira 80 mg solution for injection in pre-filled syringe with automatic needle guard 
Each 0.8 ml single dose pre-filled syringe contains 80 mg of adalimumab. 
 
Humira 80 mg solution for injection in pre-filled pen 
Each 0.8 ml single dose pre-filled pen contains 80 mg of adalimumab.  
 
Adalimumab is a recombinant human monoclonal antibody produced in Chinese Hamster Ovary cells. 
 
For the full list of excipients, see section 6.1.  
 
 
3. PHARMACEUTICAL FORM  
 
Solution for injection. (injection) 
Clear, colourless solution.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications  
 
Rheumatoid arthritis 
 
Humira in combination with methotrexate, is indicated for: 
 
 the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the response 

to disease-modifying anti-rheumatic drugs including methotrexate has been inadequate. 
 the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated 

with methotrexate. 
 
Humira can be given as monotherapy in case of intolerance to methotrexate or when continued treatment 
with methotrexate is inappropriate. 
 
Humira has been shown to reduce the rate of progression of joint damage as measured by X-ray and to 
improve physical function, when given in combination with methotrexate. 
 
Psoriasis 
 
Humira is indicated for the treatment of moderate to severe chronic plaque psoriasis in adult patients who 
are candidates for systemic therapy. 
 



216 

Hidradenitis suppurativa (HS) 
 
Humira is indicated for the treatment of active moderate to severe hidradenitis suppurativa (acne inversa) 
in adults and adolescents from 12 years of age with an inadequate response to conventional systemic HS 
therapy (see sections 5.1 and 5.2). 
 
Crohn’s disease 
 
Humira is indicated for treatment of moderately to severely active Crohn’s disease, in adult patients who 
have not responded despite a full and adequate course of therapy with a corticosteroid and/or an 
immunosuppressant; or who are intolerant to or have medical contraindications for such therapies.  
 
Paediatric Crohn's disease  
 
Humira is indicated for the treatment of moderately to severely active Crohn's disease in paediatric 
patients (from 6 years of age) who have had an inadequate response to conventional therapy including 
primary nutrition therapy and a corticosteroid and/or an immunomodulator, or who are intolerant to or 
have contraindications for such therapies. 
 
Ulcerative colitis 
 
Humira is indicated for treatment of moderately to severely active ulcerative colitis in adult patients who 
have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine 
(6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such 
therapies.  
 
Paediatric ulcerative colitis 
 
Humira is indicated for the treatment of moderately to severely active ulcerative colitis in paediatric 
patients (from 6 years of age) who have had an inadequate response to conventional therapy including 
corticosteroids and/or 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have 
medical contraindications for such therapies. 
 
Uveitis 
 
Humira is indicated for the treatment of non-infectious intermediate, posterior and panuveitis in adult 
patients who have had an inadequate response to corticosteroids, in patients in need of corticosteroid-
sparing, or in whom corticosteroid treatment is inappropriate. 
 
Paediatric Uveitis 
 
Humira is indicated for the treatment of paediatric chronic non-infectious anterior uveitis in patients from 
2 years of age who have had an inadequate response to or are intolerant to conventional therapy, or in 
whom conventional therapy is inappropriate. 
 
4.2 Posology and method of administration   
 
Humira treatment should be initiated and supervised by specialist physicians experienced in the diagnosis 
and treatment of conditions for which Humira is indicated. Ophthalmologists are advised to consult with 
an appropriate specialist before initiation of treatment with Humira (see section 4.4). Patients treated with 
Humira should be given the Patient Reminder Card. 
 



217 

After proper training in injection technique, patients may self-inject with Humira if their physician 
determines that it is appropriate and with medical follow-up as necessary.  
 
During treatment with Humira, other concomitant therapies (e.g., corticosteroids and/or 
immunomodulatory agents) should be optimised. 
 
Posology 
 
Rheumatoid arthritis 
 
The recommended dose of Humira for adult patients with rheumatoid arthritis is 40 mg adalimumab 
administered every other week as a single dose via subcutaneous injection. Methotrexate should be 
continued during treatment with Humira. 
 
Glucocorticoids, salicylates, non-steroidal anti-inflammatory drugs (NSAIDs), or analgesics can be 
continued during treatment with Humira.  Regarding combination with disease modifying anti-rheumatic 
drugs other than methotrexate see sections 4.4 and 5.1. 
 
In monotherapy, some patients who experience a decrease in their response to Humira 40 mg every other 
week may benefit from an increase in dosage to 40 mg adalimumab every week or 80 mg every other 
week.  
 
Available data suggest that the clinical response is usually achieved within 12 weeks of treatment.  
Continued therapy should be reconsidered in a patient not responding within this time period. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Psoriasis 
 
The recommended dose of Humira for adult patients is an initial dose of 80 mg administered 
subcutaneously, followed by 40 mg subcutaneously given every other week starting one week after the 
initial dose. Humira 40 mg solution for injection in pre-filled syringe and/or pre-filled pen is available for 
the maintenance dose. 
 
Continued therapy beyond 16 weeks should be carefully reconsidered in a patient not responding within 
this time period. 
 
Beyond 16 weeks, patients with inadequate response to Humira 40 mg every other week may benefit from 
an increase in dosage to 40 mg every week or 80 mg every other week. The benefits and risks of continued 
40 mg weekly or 80 mg every other week therapy should be carefully reconsidered in a patient with an 
inadequate response after the increase in dosage (see section 5.1). If adequate response is achieved with 
40 mg every week or 80 mg every other week, the dosage may subsequently be reduced to 40 mg every 
other week. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Hidradenitis suppurativa 
 
The recommended Humira dose regimen for adult patients with hidradenitis suppurativa (HS) is 160 mg 
initially at Day 1 (given as two 80 mg injections in one day or as one 80 mg injection per day for two 
consecutive days), followed by 80 mg two weeks later at Day 15. Two weeks later (Day 29) continue with 



218 

a dose of 40 mg every week or 80 mg every other week. Antibiotics may be continued during treatment 
with Humira if necessary. It is recommended that the patient should use a topical antiseptic wash on their 
HS lesions on a daily basis during treatment with Humira.  
 
Continued therapy beyond 12 weeks should be carefully reconsidered in a patient with no improvement 
within this time period.   
 
Should treatment be interrupted, Humira 40 mg every week or 80 mg every other week may be re-
introduced (see section 5.1).  
 
The benefit and risk of continued long-term treatment should be periodically evaluated (see section 5.1). 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Crohn’s disease 
 
The recommended Humira induction dose regimen for adult patients with moderately to severely active 
Crohn’s disease is 80 mg at Week 0 followed by 40 mg at Week 2. In case there is a need for a more rapid 
response to therapy, the regimen 160 mg at Week 0 (given as two 80 mg injections in one day or as one 
80 mg injection per day for two consecutive days), followed by 80 mg at Week 2, can be used with the 
awareness that the risk for adverse events is higher during induction. 
 
After induction treatment, the recommended dose is 40 mg every other week via subcutaneous injection. 
Alternatively, if a patient has stopped Humira and signs and symptoms of disease recur, Humira may be 
re-administered. There is little experience from re-administration after more than 8 weeks since the 
previous dose.  
 
During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice 
guidelines. 
 
Some patients who experience decrease in their response to Humira 40 mg every other week may benefit 
from an increase in dosage to 40 mg Humira every week or 80 mg every other week. 
 
Some patients who have not responded by Week 4 may benefit from continued maintenance therapy 
through Week 12. Continued therapy should be carefully reconsidered in a patient not responding within 
this time period. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Ulcerative colitis 
 
The recommended Humira induction dose regimen for adult patients with moderate to severe ulcerative 
colitis is 160 mg at Week 0 (given as two 80 mg injections in one day or as one 80 mg injection per day 
for two consecutive days) and 80 mg at Week 2. After induction treatment, the recommended dose is 
40 mg every other week via subcutaneous injection.  
 
During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice 
guidelines.  
 
Some patients who experience decrease in their response to 40 mg every other week may benefit from an 
increase in dosage to 40 mg Humira every week or 80 mg every other week. 



219 

 
Available data suggest that clinical response is usually achieved within 2-8 weeks of treatment.  Humira 
therapy should not be continued in patients failing to respond within this time period. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Uveitis 
 
The recommended dose of Humira for adult patients with uveitis is an initial dose of 80 mg, followed by 
40 mg given every other week starting one week after the initial dose. Humira 40 mg solution for injection 
in pre-filled syringe and/or pre-filled pen is available for the maintenance dose. There is limited 
experience in the initiation of treatment with Humira alone. Treatment with Humira can be initiated in 
combination with corticosteroids and/or with other non-biologic immunomodulatory agents. Concomitant 
corticosteroids may be tapered in accordance with clinical practice starting two weeks after initiating 
treatment with Humira. 
 
It is recommended that the benefit and risk of continued long-term treatment should be evaluated on a 
yearly basis (see section 5.1).   
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Special populations 
 
Elderly 
 
No dose adjustment is required. 
 
Renal and/or hepatic impairment 
 
Humira has not been studied in these patient populations. No dose recommendations can be made. 
 
Paediatric population 
 
Paediatric plaque psoriasis 
 
The safety and efficacy of Humira in children aged 4-17 years have been established for plaque psoriasis. 
The recommended Humira dose is up to a maximum of 40 mg per dose.   
 
Adolescent hidradenitis suppurativa (from 12 years of age, weighing at least 30 kg) 
 
There are no clinical trials with Humira in adolescent patients with HS.  The posology of Humira in these 
patients has been determined from pharmacokinetic modelling and simulation (see section 5.2). 
 
The recommended Humira dose is 80 mg at Week 0 followed by 40 mg every other week starting at 
Week 1 via subcutaneous injection.  
 
In adolescent patients with inadequate response to Humira 40 mg every other week, an increase in dosage 
to 40 mg every week or 80 mg every other week may be considered.  
 



220 

Antibiotics may be continued during treatment with Humira if necessary. It is recommended that the 
patient should use a topical antiseptic wash on their HS lesions on a daily basis during treatment with 
Humira.  
 
Continued therapy beyond 12 weeks should be carefully reconsidered in a patient with no improvement 
within this time period.   
 
Should treatment be interrupted, Humira may be re-introduced as appropriate. 
 
The benefit and risk of continued long-term treatment should be periodically evaluated (see adult data in 
section 5.1) 
 
There is no relevant use of Humira in children aged less than 12 years in this indication. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Paediatric Crohn's disease 
 
The recommended dose of Humira for patients with Crohn’s disease from 6 to 17 years of age is based on 
body weight (Table 1). Humira is administered via subcutaneous injection.  
 

Table 1. Humira Dose for Paediatric Patients with Crohn’s disease 
 

Patient 
Weight 

Induction Dose Maintenance 
Dose 

Starting at 
Week 4

< 40 kg  40 mg at Week 0 and 20 mg at Week 2 
 

In case there is a need for a more rapid response to therapy with the 
awareness that the risk for adverse events may be higher with use of the 
higher induction dose, the following dose may be used: 
 80 mg at Week 0 and 40 mg at Week 2

20 mg every 
other week 

≥ 40 kg  80 mg at Week 0 and 40 mg at Week 2 
 

In case there is a need for a more rapid response to therapy with the 
awareness that the risk for adverse events may be higher with use of the 
higher induction dose, the following dose may be used: 
 160 mg at Week 0 and 80 mg at Week 2

40 mg every 
other week 

 
Patients who experience insufficient response may benefit from an increase in dosage: 
 < 40 kg: 20 mg every week 
 ≥ 40 kg: 40 mg every week or 80 mg every other week 
 
Continued therapy should be carefully considered in a subject not responding by Week 12. 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
There is no relevant use of Humira in children aged less than 6 years for this indication. 
 



221 

Paediatric ulcerative colitis  
 
The recommended dose of Humira for patients from 6 to 17 years of age with ulcerative colitis is based on 
body weight (Table 2). Humira is administered via subcutaneous injection.  
 

Table 2. Humira Dose for Paediatric Patients with Ulcerative Colitis  

Patient Weight Induction Dose 
Maintenance Dose 

Starting at Week 4* 
< 40 kg • 80 mg at Week 0 (given as one 80 

mg injection) and 
• 40 mg at Week 2 (given as one 40 

mg injection)

• 40 mg every other week 

≥ 40 kg • 160 mg at Week 0 (given as two 
80 mg injections in one day or one 
80 mg injection per day for two 
consecutive days) and 

• 80 mg at Week 2 (given as one 80 
mg injection)

• 80 mg every other week 

* Paediatric patients who turn 18 years of age while on Humira should continue their prescribed 
maintenance dose. 

  

Continued therapy beyond 8 weeks should be carefully considered in patients not showing signs of 
response within this time period. 
 
There is no relevant use of Humira in children aged less than 6 years in this indication. 
 
Humira may be available in different strengths and/or presentations depending on the individual treatment 
needs.  
 
Paediatric Uveitis  
 
The recommended dose of Humira for paediatric patients with uveitis from 2 years of age is based on 
body weight (Table 3). Humira is administered via subcutaneous injection. 
 
In paediatric uveitis, there is no experience in the treatment with Humira without concomitant treatment 
with methotrexate. 

 
Table 3. Humira Dose for Paediatric Patients with Uveitis 

 
Patient Weight Dosing Regimen 

< 30 kg 20 mg every other week in 
combination with methotrexate 

≥ 30 kg 40 mg every other week in 
combination with methotrexate 

 
When Humira therapy is initiated, a loading dose of 40 mg for patients < 30 kg or 80 mg for patients 
≥ 30 kg may be administered one week prior to the start of maintenance therapy. No clinical data are 
available on the use of a Humira loading dose in children < 6 years of age (see section 5.2). 
 
There is no relevant use of Humira in children aged less than 2 years in this indication. 
 



222 

It is recommended that the benefit and risk of continued long-term treatment should be evaluated on a 
yearly basis (see section 5.1). 
 
Humira may be available in other strengths and/or presentations depending on the individual treatment 
needs. 
 
Method of administration 
 
Humira is administered by subcutaneous injection. Full instructions for use are provided in the package 
leaflet. 
 
Humira is available in other strengths and presentations. 
 
4.3 Contraindications  
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  
 
Active tuberculosis or other severe infections such as sepsis, and opportunistic infections (see section 4.4). 
 
Moderate to severe heart failure (NYHA class III/IV) (see section 4.4). 
 
4.4 Special warnings and precautions for use 
 
Traceability  
 
In order to improve traceability of biological medicinal products, the name and the batch number of the 
administered product should be clearly recorded. 
 
Infections 
 
Patients taking TNF-antagonists are more susceptible to serious infections. Impaired lung function may 
increase the risk for developing infections. Patients must therefore be monitored closely for infections, 
including tuberculosis, before, during and after treatment with Humira.  Because the elimination of 
adalimumab may take up to four months, monitoring should be continued throughout this period. 
 
Treatment with Humira should not be initiated in patients with active infections including chronic or 
localised infections until infections are controlled. In patients who have been exposed to tuberculosis and 
patients who have travelled in areas of high risk of tuberculosis or endemic mycoses, such as 
histoplasmosis, coccidioidomycosis, or blastomycosis, the risk and benefits of treatment with Humira 
should be considered prior to initiating therapy (see Other opportunistic infections). 
 
Patients who develop a new infection while undergoing treatment with Humira should be monitored 
closely and undergo a complete diagnostic evaluation. Administration of Humira should be discontinued if 
a patient develops a new serious infection or sepsis, and appropriate antimicrobial or antifungal therapy 
should be initiated until the infection is controlled.  Physicians should exercise caution when considering 
the use of Humira in patients with a history of recurring infection or with underlying conditions which 
may predispose patients to infections, including the use of concomitant immunosuppressive medications. 
 



223 

Serious infections 
 
Serious infections, including sepsis, due to bacterial, mycobacterial, invasive fungal, parasitic, viral, or 
other opportunistic infections such as listeriosis, legionellosis and pneumocystis have been reported in 
patients receiving Humira.   
 
Other serious infections seen in clinical trials include pneumonia, pyelonephritis, septic arthritis and 
septicaemia. Hospitalisation or fatal outcomes associated with infections have been reported.  
 
Tuberculosis 
 
Tuberculosis, including reactivation and new onset of tuberculosis, has been reported in patients receiving 
Humira.  Reports included cases of pulmonary and extra-pulmonary (i.e. disseminated) tuberculosis.  
 
Before initiation of therapy with Humira, all patients must be evaluated for both active or inactive 
(“latent”) tuberculosis infection.  This evaluation should include a detailed medical assessment of patient 
history of tuberculosis or possible previous exposure to people with active tuberculosis and previous 
and/or current immunosuppressive therapy.  Appropriate screening tests (i.e. tuberculin skin test and chest 
X-ray) should be performed in all patients (local recommendations may apply).  It is recommended that 
the conduct and results of these tests are recorded in the Patient Reminder Card.  Prescribers are reminded 
of the risk of false negative tuberculin skin test results, especially in patients who are severely ill or 
immunocompromised.  
 
If active tuberculosis is diagnosed, Humira therapy must not be initiated (see section 4.3).  
 
In all situations described below, the benefit/risk balance of therapy should be very carefully considered. 
 
If latent tuberculosis is suspected, a physician with expertise in the treatment of tuberculosis should be 
consulted.   
 
If latent tuberculosis is diagnosed, appropriate treatment must be started with anti-tuberculosis prophylaxis 
treatment before the initiation of Humira, and in accordance with local recommendations.  
 
Use of anti-tuberculosis prophylaxis treatment should also be considered before the initiation of Humira in 
patients with several or significant risk factors for tuberculosis despite a negative test for tuberculosis and 
in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment 
cannot be confirmed.   
 
Despite prophylactic treatment for tuberculosis, cases of reactivated tuberculosis have occurred in patients 
treated with Humira. Some patients who have been successfully treated for active tuberculosis have 
redeveloped tuberculosis while being treated with Humira. 
 
Patients should be instructed to seek medical advice if signs/symptoms suggestive of a tuberculosis 
infection (e.g., persistent cough, wasting/weight loss, low grade fever, listlessness) occur during or after 
therapy with Humira.  
 
Other opportunistic infections 
 
Opportunistic infections, including invasive fungal infections have been observed in patients receiving 
Humira. These infections have not consistently been recognised in patients taking TNF-antagonists and 
this has resulted in delays in appropriate treatment, sometimes resulting in fatal outcomes.  
 



224 

For patients who develop the signs and symptoms such as fever, malaise, weight loss, sweats, cough, 
dyspnoea, and/or pulmonary infiltrates or other serious systemic illness with or without concomitant shock 
an invasive fungal infection should be suspected and administration of Humira should be promptly 
discontinued.  Diagnosis and administration of empiric antifungal therapy in these patients should be made 
in consultation with a physician with expertise in the care of patients with invasive fungal infections.  
 
Hepatitis B reactivation 
 
Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including Humira, who are 
chronic carriers of this virus (i.e. surface antigen positive).  Some cases have had a fatal outcome. Patients 
should be tested for HBV infection before initiating treatment with Humira. For patients who test positive 
for hepatitis B infection, consultation with a physician with expertise in the treatment of hepatitis B is 
recommended. 
 
Carriers of HBV who require treatment with Humira should be closely monitored for signs and symptoms 
of active HBV infection throughout therapy and for several months following termination of therapy. 
Adequate data from treating patients who are carriers of HBV with anti-viral therapy in conjunction with 
TNF-antagonist therapy to prevent HBV reactivation are not available. In patients who develop HBV 
reactivation, Humira should be stopped and effective anti-viral therapy with appropriate supportive 
treatment should be initiated.  
 
Neurological events  
 
TNF-antagonists including Humira have been associated in rare instances with new onset or exacerbation 
of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease 
including multiple sclerosis and optic neuritis, and peripheral demyelinating disease, including Guillain-
Barré syndrome. Prescribers should exercise caution in considering the use of Humira in patients with pre-
existing or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of 
Humira should be considered if any of these disorders develop. There is a known association between 
intermediate uveitis and central demyelinating disorders. Neurologic evaluation should be performed in 
patients with non-infectious intermediate uveitis prior to the initiation of Humira therapy and regularly 
during treatment to assess for pre-existing or developing central demyelinating disorders.  
 
Allergic reactions 
 
Serious allergic reactions associated with Humira were rare during clinical trials. Non-serious allergic 
reactions associated with Humira were uncommon during clinical trials. Reports of serious allergic 
reactions including anaphylaxis have been received following Humira administration. If an anaphylactic 
reaction or other serious allergic reaction occurs, administration of Humira should be discontinued 
immediately and appropriate therapy initiated.  
 
Immunosuppression 
 
In a study of 64 patients with rheumatoid arthritis that were treated with Humira, there was no evidence of 
depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or change in 
enumeration of effector T-, B-, NK-cells, monocyte/macrophages, and neutrophils. 
 
Malignancies and lymphoproliferative disorders 
 
In the controlled portions of clinical trials of TNF-antagonists, more cases of malignancies including 
lymphoma have been observed among patients receiving a TNF-antagonist compared with control 
patients. However, the occurrence was rare. In the post marketing setting, cases of leukaemia have been 
reported in patients treated with a TNF-antagonist. There is an increased background risk for lymphoma 



225 

and leukaemia in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, 
which complicates the risk estimation. With the current knowledge, a possible risk for the development of 
lymphomas, leukaemia, and other malignancies in patients treated with a TNF-antagonist cannot be 
excluded. 
 
Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 
22 years of age) treated with TNF-antagonists (initiation of therapy ≤ 18 years of age), including 
adalimumab in the post marketing setting. Approximately half the cases were lymphomas. The other cases 
represented a variety of different malignancies and included rare malignancies usually associated with 
immunosuppression. A risk for the development of malignancies in children and adolescents treated with 
TNF-antagonists cannot be excluded.  
 
Rare postmarketing cases of hepatosplenic T-cell lymphoma have been identified in patients treated with 
adalimumab. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. 
Some of these hepatosplenic T-cell lymphomas with Humira have occurred in young adult patients on 
concomitant treatment with azathioprine or 6-mercaptopurine used for inflammatory bowel disease. The 
potential risk with the combination of azathioprine or 6-mercaptopurine and Humira should be carefully 
considered. A risk for the development of hepatosplenic T-cell lymphoma in patients treated with Humira 
cannot be excluded (see section 4.8). 
 
No studies have been conducted that include patients with a history of malignancy or in whom treatment 
with Humira is continued following development of malignancy.  Thus, additional caution should be 
exercised in considering Humira treatment of these patients (see section 4.8). 
 
All patients, and in particular patients with a medical history of extensive immunosuppressant therapy or 
psoriasis patients with a history of PUVA treatment should be examined for the presence of non-
melanoma skin cancer prior to and during treatment with Humira.  Melanoma and Merkel cell carcinoma 
have also been reported in patients treated with TNF-antagonists including adalimumab (see section 4.8). 
 
In an exploratory clinical trial evaluating the use of another TNF-antagonist, infliximab, in patients with 
moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, mostly in the lung 
or head and neck, were reported in infliximab-treated patients compared with control patients. All patients 
had a history of heavy smoking. Therefore, caution should be exercised when using any TNF-antagonist in 
COPD patients, as well as in patients with increased risk for malignancy due to heavy smoking. 
 
With current data it is not known if adalimumab treatment influences the risk for developing dysplasia or 
colon cancer.  All patients with ulcerative colitis who are at increased risk for dysplasia or colon 
carcinoma (for example, patients with long-standing ulcerative colitis or primary sclerosing cholangitis), 
or who had a prior history of dysplasia or colon carcinoma should be screened for dysplasia at regular 
intervals before therapy and throughout their disease course. This evaluation should include colonoscopy 
and biopsies per local recommendations. 
 
Haematologic reactions 
 
Rare reports of pancytopenia including aplastic anaemia have been reported with TNF-antagonists.  
Adverse events of the haematologic system, including medically significant cytopenia (e.g. 
thrombocytopenia, leukopenia) have been reported with Humira. All patients should be advised to seek 
immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias (e.g. 
persistent fever, bruising, bleeding, pallor) while on Humira. Discontinuation of Humira therapy should be 
considered in patients with confirmed significant haematologic abnormalities. 
 
Vaccinations  
 



226 

Similar antibody responses to the standard 23-valent pneumococcal vaccine and the influenza trivalent 
virus vaccination were observed in a study in 226 adult subjects with rheumatoid arthritis who were 
treated with adalimumab or placebo. No data are available on the secondary transmission of infection by 
live vaccines in patients receiving Humira.   
 
It is recommended that paediatric patients, if possible, be brought up to date with all immunisations in 
agreement with current immunisation guidelines prior to initiating Humira therapy. 
 
Patients on Humira may receive concurrent vaccinations, except for live vaccines. Administration of live 
vaccines (e.g., BCG vaccine) to infants exposed to adalimumab in utero is not recommended for 5 months 
following the mother’s last adalimumab injection during pregnancy. 
 
Congestive heart failure 
 
In a clinical trial with another TNF-antagonist worsening congestive heart failure and increased mortality 
due to congestive heart failure have been observed. Cases of worsening congestive heart failure have also 
been reported in patients receiving Humira. Humira should be used with caution in patients with mild 
heart failure (NYHA class I/II). Humira is contraindicated in moderate to severe heart failure (see section 
4.3). Treatment with Humira must be discontinued in patients who develop new or worsening symptoms 
of congestive heart failure. 
 
Autoimmune processes 
 
Treatment with Humira may result in the formation of autoimmune antibodies. The impact of long-term 
treatment with Humira on the development of autoimmune diseases is unknown. If a patient develops 
symptoms suggestive of a lupus-like syndrome following treatment with Humira and is positive for 
antibodies against double-stranded DNA, further treatment with Humira should not be given (see section 
4.8). 
 
Concurrent administration of biologic DMARDS or TNF-antagonists 
 
Serious infections were seen in clinical studies with concurrent use of anakinra and another 
TNF-antagonist, etanercept, with no added clinical benefit compared to etanercept alone. Because of the 
nature of the adverse events seen with the combination of etanercept and anakinra therapy, similar 
toxicities may also result from the combination of anakinra and other TNF-antagonists. Therefore, the 
combination of adalimumab and anakinra is not recommended. (See section 4.5). 
 
Concomitant administration of adalimumab with other biologic DMARDS (e.g, anakinra and abatacept) or 
other TNF-antagonists is not recommended based upon the possible increased risk for infections, 
including serious infections and other potential pharmacological interactions. (See section 4.5). 
 
Surgery 
 
There is limited safety experience of surgical procedures in patients treated with Humira. The long half-
life of adalimumab should be taken into consideration if a surgical procedure is planned.  A patient who 
requires surgery while on Humira should be closely monitored for infections, and appropriate actions 
should be taken. There is limited safety experience in patients undergoing arthroplasty while receiving 
Humira.  
 



227 

Small bowel obstruction 
 
Failure to respond to treatment for Crohn’s disease may indicate the presence of fixed fibrotic stricture 
that may require surgical treatment. Available data suggest that Humira does not worsen or cause 
strictures. 
 
Elderly 
 
The frequency of serious infections among Humira treated subjects over 65 years of age (3.7%) was 
higher than for those under 65 years of age (1.5%). Some of those had a fatal outcome. Particular attention 
regarding the risk for infection should be paid when treating the elderly. 
 
Paediatric population 
 
See Vaccinations above. 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
Humira has been studied in rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and psoriatic 
arthritis patients taking Humira as monotherapy and those taking concomitant methotrexate.  Antibody 
formation was lower when Humira was given together with methotrexate in comparison with use as 
monotherapy. Administration of Humira without methotrexate resulted in increased formation of 
antibodies, increased clearance and reduced efficacy of adalimumab (see section 5.1).  
 
The combination of Humira and anakinra is not recommended (see section 4.4 “Concurrent administration 
of biologic DMARDS or TNF-antagonists”).  
 
The combination of Humira and abatacept is not recommended (see section 4.4 “Concurrent 
administration of biologic DMARDS or TNF-antagonists”). 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential 
 
Women of childbearing potential should consider the use of adequate contraception to prevent pregnancy 
and continue its use for at least five months after the last Humira treatment. 
 
Pregnancy 
 
A large number (approximately 2100) of prospectively collected pregnancies exposed to adalimumab 
resulting in live birth with known outcomes, including more than 1500 exposed during the first trimester, 
does not indicate an increase in the rate of malformation in the newborn. 
 
In a prospective cohort registry, 257 women with rheumatoid arthritis (RA) or Crohn’s disease (CD) 
treated with adalimumab at least during the first trimester and 120 women with RA or CD not treated with 
adalimumab were enrolled.  The primary endpoint was the birth prevalence of major birth defects. The 
rate of pregnancies ending with at least one live born infant with a major birth defect was 6/69 (8.7%) in 
the adalimumab-treated women with RA and 5/74 (6.8%) in the untreated women with RA (unadjusted 
OR 1.31, 95% CI 0.38-4.52) and 16/152 (10.5%) in the adalimumab-treated women with CD and 3/32 
(9.4%) in the untreated women with CD (unadjusted OR 1.14, 95% CI 0.31-4.16). The adjusted OR 
(accounting for baseline differences) was 1.10 (95% CI 0.45-2.73) with RA and CD combined. There were 
no distinct differences between adalimumab-treated and untreated women for the secondary endpoints 
spontaneous abortions, minor birth defects, preterm delivery, birth size and serious or opportunistic 



228 

infections and no stillbirths or malignancies were reported. The interpretation of data may be impacted due 
to methodological limitations of the study, including small sample size and non-randomized design. 
 
In a developmental toxicity study conducted in monkeys, there was no indication of maternal toxicity, 
embryotoxicity or teratogenicity. Preclinical data on postnatal toxicity of adalimumab are not available 
(see section 5.3). 
 
Due to its inhibition of TNF, adalimumab administered during pregnancy could affect normal immune 
responses in the newborn.  Adalimumab should only be used during pregnancy if clearly needed. 
 
Adalimumab may cross the placenta into the serum of infants born to women treated with adalimumab 
during pregnancy. Consequently, these infants may be at increased risk for infection. Administration of 
live vaccines (e.g., BCG vaccine) to infants exposed to adalimumab in utero is not recommended for 
5 months following the mother’s last adalimumab injection during pregnancy. 
 
Breast-feeding 
 
Limited information from the published literature indicates that adalimumab is excreted in breast milk at 
very low concentrations with the presence of adalimumab in human milk at concentrations of 0.1% to 1% 
of the maternal serum level. Given orally, immunoglobulin G proteins undergo intestinal proteolysis and 
have poor bioavailability. No effects on the breastfed newborns/infants are anticipated. Consequently, 
Humira can be used during breastfeeding. 
 
Fertility 
 
Preclinical data on fertility effects of adalimumab are not available. 
 
4.7 Effects on ability to drive and use machines  
 
Humira may have a minor influence on the ability to drive and use machines. Vertigo and visual 
impairment may occur following administration of Humira (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Humira was studied in 9,506 patients in pivotal controlled and open label trials for up to 60 months or 
more.  These trials included rheumatoid arthritis patients with short term and long standing disease, 
juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis) as 
well as axial spondyloarthritis (ankylosing spondylitis and axial spondyloarthritis without radiographic 
evidence of AS), psoriatic arthritis, Crohn’s disease, ulcerative colitis, psoriasis, hidradenitis suppurativa 
and uveitis patients. The pivotal controlled studies involved 6,089 patients receiving Humira and 3,801 
patients receiving placebo or active comparator during the controlled period. 
 
The proportion of patients who discontinued treatment due to adverse events during the double-blind, 
controlled portion of pivotal studies was 5.9% for patients taking Humira and 5.4% for control treated 
patients. 
 
The most commonly reported adverse reactions are infections (such as nasopharyngitis, upper respiratory 
tract infection and sinusitis), injection site reactions (erythema, itching, haemorrhage, pain or swelling), 
headache and musculoskeletal pain. 
 



229 

Serious adverse reactions have been reported for Humira. TNF-antagonists, such as Humira affect the 
immune system and their use may affect the body’s defence against infection and cancer. 
Fatal and life-threatening infections (including sepsis, opportunistic infections and TB), HBV reactivation 
and various malignancies (including leukaemia, lymphoma and HSTCL) have also been reported with use 
of Humira. 
 
Serious haematological, neurological and autoimmune reactions have also been reported. These include 
rare reports of pancytopenia, aplastic anaemia, central and peripheral demyelinating events and reports of 
lupus, lupus-related conditions and Stevens-Johnson syndrome. 
 
Paediatric population 
 
In general, the adverse events in paediatric patients were similar in frequency and type to those seen in 
adult patients. 
 
Tabulated list of adverse reactions 
 
The following list of adverse reactions is based on experience from clinical trials and on postmarketing 
experience and are displayed by system organ class and frequency in Table 4 below: very common 
( 1/10); common ( 1/100 to < 1/10); uncommon ( 1/1,000 to < 1/100); rare ( 1/10,000 to < 1/1,000); 
and not known (cannot be estimated from the available data). Within each frequency grouping, 
undesirable effects are presented in order of decreasing seriousness. The highest frequency seen among the 
various indications has been included. An asterisk (*) appears in the SOC column if further information is 
found elsewhere in sections 4.3, 4.4 and 4.8. 
 

Table 4 
Undesirable Effects 

 

System Organ Class Frequency Adverse Reaction 

Infections and 
infestations* 

 

Very common Respiratory tract infections (including lower and 
upper respiratory tract infection, pneumonia, 
sinusitis, pharyngitis, nasopharyngitis and 
pneumonia herpes viral) 

Common 

 

Systemic infections (including sepsis, candidiasis 
and influenza), 
intestinal infections (including gastroenteritis 
viral), 
skin and soft tissue infections (including 
paronychia, cellulitis, impetigo, necrotising 
fasciitis and herpes zoster), 
ear infections, 
oral infections (including herpes simplex, oral 
herpes and tooth infections),  
reproductive tract infections (including 
vulvovaginal mycotic infection),  

urinary tract infections (including 
pyelonephritis), 

fungal infections, 

joint infections 



230 

System Organ Class Frequency Adverse Reaction 

Uncommon 
 

Neurological infections (including viral 
meningitis), 
opportunistic infections and tuberculosis 
(including coccidioidomycosis, histoplasmosis 
and mycobacterium avium complex infection),  
bacterial infections, 
eye infections, 
diverticulitis1)  

Neoplasms benign, 
malignant and unspecified 
(including cysts and 
polyps)* 

Common 

 

Skin cancer excluding melanoma (including 
basal cell carcinoma and squamous cell 
carcinoma), 

benign neoplasm 

Uncommon 
 

Lymphoma**,  
solid organ neoplasm (including breast cancer, 
lung neoplasm and thyroid neoplasm),  
melanoma** 

 Rare Leukaemia1) 

Not known Hepatosplenic T-cell lymphoma1) 

Merkel cell carcinoma (neuroendocrine 
carcinoma of the skin)1), 

Kaposi’s sarcoma 

Blood and the lymphatic 
system disorders* 

Very common 

 

Leukopenia (including neutropenia and 
agranulocytosis),  

anaemia 

 
Common Leucocytosis, 

thrombocytopenia 

Uncommon Idiopathic thrombocytopenic purpura 

Rare 
 

Pancytopenia 

Immune system disorders* Common 

 

Hypersensitivity, 

allergies (including seasonal allergy) 

Uncommon Sarcoidosis1), 

vasculitis 

Rare Anaphylaxis1) 

Metabolism and nutrition Very common Lipids increased



231 

System Organ Class Frequency Adverse Reaction 

disorders  

Common Hypokalaemia,  

uric acid increased,  

blood sodium abnormal, 

hypocalcaemia, 

hyperglycaemia, 

hypophosphatemia, 

dehydration 

Psychiatric disorders Common 

 

Mood alterations (including depression),  

anxiety, 

insomnia 

Nervous system disorders* Very common 

 

Headache 

Common 

 

Paraesthesias (including hypoesthesia), 

migraine, 

nerve root compression 

Uncommon 
 

Cerebrovascular accident1), 
tremor, 
neuropathy   

Rare 
 

Multiple sclerosis, 

demyelinating disorders (e.g. optic neuritis, 
Guillain-Barré syndrome) 1) 

Eye disorders Common 

 

Visual impairment, 

conjunctivitis, 

blepharitis, 

eye swelling 

Uncommon Diplopia 

Ear and labyrinth 
disorders  

 

Common 

 

Vertigo 

Uncommon 
 

Deafness,  
tinnitus 

Cardiac disorders*  Common Tachycardia 

Uncommon Myocardial infarction1),



232 

System Organ Class Frequency Adverse Reaction 

 arrhythmia, 

congestive heart failure 

Rare 
 

Cardiac arrest 

Vascular disorders Common 

 

Hypertension,  

flushing,  

haematoma 

Uncommon Aortic aneurysm, 
vascular arterial occlusion, 
thrombophlebitis    

Respiratory, thoracic and 
mediastinal disorders* 

Common 

 

Asthma, 

dyspnoea, 

cough 

Uncommon 
 

Pulmonary embolism1), 
interstitial lung disease,  
chronic obstructive pulmonary disease, 
pneumonitis, 
pleural effusion1) 

Rare Pulmonary fibrosis1)

Gastrointestinal disorders Very common 

 

Abdominal pain,  

nausea and vomiting 

Common 
 

GI haemorrhage,  
dyspepsia,  
gastroesophageal reflux disease, 
sicca syndrome 

Uncommon 
 

Pancreatitis,  
dysphagia, 
face oedema 

Rare Intestinal perforation1) 

Hepato-biliary disorders* Very Common 

 

Elevated liver enzymes 

Uncommon 
 

Cholecystitis and cholelithiasis, 
hepatic steatosis, 
bilirubin increased 

Rare Hepatitis



233 

System Organ Class Frequency Adverse Reaction 

 reactivation of hepatitis B1)  

autoimmune hepatitis1) 

Not known 

 

Liver failure1) 

Skin and subcutaneous 
tissue disorders 

Very Common 

 

Rash (including exfoliative rash) 

Common 
 

Worsening or new onset of psoriasis (including 
palmoplantar pustular psoriasis)1), 
urticaria, 
bruising (including purpura),  
dermatitis (including eczema), 
onychoclasis,  
hyperhidrosis, 
alopecia1), 
pruritus  

Uncommon 
 

Night sweats, 
scar 

Rare Erythema multiforme1), 

Stevens-Johnson syndrome1), 

angioedema1), 

cutaneous vasculitis1) 

lichenoid skin reaction1) 

Not known Worsening of symptoms of dermatomyositis1) 

Musculoskeletal and 
connective tissue disorders 

Very common 

 

Musculoskeletal pain 

Common Muscle spasms (including blood creatine 
phosphokinase increased) 

Uncommon Rhabdomyolysis, 
systemic lupus erythematosus 

Rare 
 

Lupus-like syndrome1)

Renal and urinary 
disorders  

Common 

 

Renal impairment, 

haematuria 

Uncommon 
 

Nocturia 

Reproductive system and 
breast disorders 

Uncommon Erectile dysfunction 



234 

System Organ Class Frequency Adverse Reaction 

General disorders and 
administration site 
conditions* 

Very Common 

 

Injection site reaction (including injection site 
erythema) 

Common 
 

Chest pain,  
oedema, 
pyrexia1) 

Uncommon 
 

Inflammation 

Investigations* Common Coagulation and bleeding disorders (including 
activated partial thromboplastin time prolonged), 

autoantibody test positive (including double 
stranded DNA antibody),  

blood lactate dehydrogenase increased 

Injury, poisoning and 
procedural complications 

Common Impaired healing 

 
* further information is found elsewhere in sections 4.3, 4.4 and 4.8 
** including open label extension studies 
1) including spontaneous reporting data 
 
Hidradenitis suppurativa 
 
The safety profile for patients with HS treated with Humira weekly was consistent with the known safety 
profile of Humira. 
 
Uveitis 
 
The safety profile for patients with uveitis treated with Humira every other week was consistent with the 
known safety profile of Humira. 
 
Description of selected adverse reactions 
 
Injection site reactions 
 
In the pivotal controlled trials in adults and children, 12.9% of patients treated with Humira developed 
injection site reactions (erythema and/or itching, haemorrhage, pain or swelling), compared to 7.2% of 
patients receiving placebo or active control. Injection site reactions generally did not necessitate 
discontinuation of the medicinal product. 
 
Infections  
 
In the pivotal controlled trials in adults and children, the rate of infection was 1.51 per patient year in the 
Humira treated patients and 1.46 per patient year in the placebo and active control-treated patients. The 
infections consisted primarily of nasopharyngitis, upper respiratory tract infection, and sinusitis. Most 
patients continued on Humira after the infection resolved. 
 



235 

The incidence of serious infections was 0.04 per patient year in Humira treated patients and 0.03 per 
patient year in placebo and active control − treated patients. 
 
In controlled and open label adult and paediatric studies with Humira, serious infections (including fatal 
infections, which occurred rarely) have been reported, which include reports of tuberculosis (including 
miliary and extra-pulmonary locations) and invasive opportunistic infections (e.g. disseminated or 
extrapulmonary histoplasmosis, blastomycosis, coccidioidomycosis, pneumocystis, candidiasis, 
aspergillosis and listeriosis). Most of the cases of tuberculosis occurred within the first eight months after 
initiation of therapy and may reflect recrudescence of latent disease. 
 
Malignancies and lymphoproliferative disorders 
 
No malignancies were observed in 249 paediatric patients with an exposure of 655.6 patient years during 
Humira trials in patients with juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and 
enthesitis-related arthritis). In addition, no malignancies were observed in 192 paediatric patients with an 
exposure of 498.1 patient years during Humira trials in paediatric patients with Crohn’s disease. No 
malignancies were observed in 77 paediatric patients with an exposure of 80.0 patient years during a 
Humira trial in paediatric patients with chronic plaque psoriasis. No malignancies were observed in 93 
paediatric patients with an exposure of 65.3 patient years during a Humira trial in paediatric patients with 
ulcerative colitis. No malignancies were observed in 60 paediatric patients with an exposure of 58.4 
patient years during a Humira trial in paediatric patients with uveitis. 
 
During the controlled portions of pivotal Humira trials in adults of at least 12 weeks in duration in patients 
with moderately to severely active rheumatoid arthritis, ankylosing spondylitis, axial spondyloarthritis 
without radiographic evidence of AS,  psoriatic arthritis, psoriasis, hidradenitis suppurativa, Crohn’s 
disease, ulcerative colitis and uveitis, malignancies, other than lymphoma and non-melanoma skin cancer, 
were observed at a rate (95% confidence interval) of 6.8 (4.4, 10.5)  per 1,000 patient-years among 5,291 
Humira treated patients versus a rate of 6.3 (3.4, 11.8) per 1,000 patient-years among 3,444 control 
patients (median duration of treatment was 4.0 months for Humira and 3.8 months for control-treated 
patients). The rate (95% confidence interval) of non-melanoma skin cancers was 8.8 (6.0, 13.0) per 1,000 
patient-years among Humira-treated patients and 3.2 (1.3, 7.6) per 1,000 patient-years among control 
patients. Of these skin cancers, squamous cell carcinomas occurred at rates (95% confidence interval) of 
2.7 (1.4, 5.4) per 1,000 patient-years among Humira-treated patients and 0.6 (0.1, 4.5) per 1,000 patient-
years among control patients. The rate (95% confidence interval) of lymphomas was 0.7 (0.2, 2.7) per 
1,000 patient-years among Humira-treated patients and 0.6 (0.1, 4.5) per 1,000 patient-years among 
control patients. 
 
When combining controlled portions of these trials and ongoing and completed open label extension 
studies with a median duration of approximately 3.3 years including 6,427 patients and over 26,439 
patient-years of therapy, the observed rate of malignancies, other than lymphoma and non-melanoma skin 
cancers is approximately 8.5 per 1,000 patient years. The observed rate of non-melanoma skin cancers is 
approximately 9.6 per 1,000 patient years, and the observed rate of lymphomas is approximately 1.3 per 
1,000 patient years. 
 
In post-marketing experience from January 2003 to December 2010, predominantly in patients with 
rheumatoid arthritis, the reported rate of malignancies is approximately 2.7 per 1,000 patient treatment 
years. The reported rates for non-melanoma skin cancers and lymphomas are approximately 0.2 and 0.3 
per 1,000 patient treatment years, respectively (see section 4.4). 
 
Rare post-marketing cases of hepatosplenic T-cell lymphoma have been reported in patients treated with 
adalimumab (see section 4.4). 
 
Autoantibodies  



236 

 
Patients had serum samples tested for autoantibodies at multiple time points in rheumatoid arthritis studies 
I − V. In these trials, 11.9% of patients treated with Humira and 8.1% of placebo and active 
control − treated patients that had negative baseline anti-nuclear antibody titres reported positive titres at 
Week 24. Two patients out of 3,441 treated with Humira in all rheumatoid arthritis and psoriatic arthritis 
studies developed clinical signs suggestive of new-onset lupus-like syndrome. The patients improved 
following discontinuation of therapy. No patients developed lupus nephritis or central nervous system 
symptoms. 
 
Hepato-biliary events 
 
In controlled Phase 3 trials of Humira in patients with rheumatoid arthritis and psoriatic arthritis with a 
control period duration ranging from 4 to 104 weeks, ALT elevations ≥ 3 x ULN occurred in 3.7% of 
Humira-treated patients and 1.6% of control-treated patients.  
 
In controlled Phase 3 trials of Humira in patients with polyarticular juvenile idiopathic arthritis who were 
4 to 17 years and enthesitis-related arthritis who were 6 to 17 years, ALT elevations ≥ 3 x ULN occurred 
in 6.1% of Humira-treated patients and 1.3% of control-treated patients. Most ALT elevations occurred 
with concomitant methotrexate use. No ALT elevations ≥ 3 x ULN occurred in the Phase 3 trial of Humira 
in patients with polyarticular juvenile idiopathic arthritis who were 2 to < 4 years. 
 
In controlled Phase 3 trials of Humira in patients with Crohn’s disease and ulcerative colitis with a control 
period ranging from 4 to 52 weeks. ALT elevations ≥ 3 x ULN occurred in 0.9% of Humira-treated 
patients and 0.9% of controlled-treated patients.  
 
In the Phase 3 trial of Humira in patients with paediatric Crohn’s disease which evaluated efficacy and 
safety of two body weight adjusted maintenance dose regimens following body weight adjusted induction 
therapy up to 52 weeks of treatment, ALT elevations ≥ 3 x ULN occurred in 2.6%  (5/192) of patients of 
whom 4 were receiving concomitant immunosuppressants at baseline. 
 
In controlled Phase 3 trials of Humira in patients with plaque psoriasis with a control period duration 
ranging from 12 to 24 weeks, ALT elevations ≥ 3 x ULN occurred in 1.8% of Humira-treated patients and 
1.8% of control-treated patients.  
 
No ALT elevations ≥ 3 X ULN occurred in the Phase 3 trial of Humira in paediatric patients with plaque 
psoriasis. 
 
In controlled trials of Humira (initial doses of 160 mg at Week 0 and 80 mg at Week 2, followed by 40 mg 
every week starting at Week 4), in patients with hidradenitis suppurativa with a control period duration 
ranging from 12 to 16 weeks, ALT elevations ≥ 3 x ULN occurred in 0.3% of Humira-treated patients and 
0.6% of control-treated patients. 
 
In controlled trials of Humira (initial doses of 80 mg at Week 0 followed by 40 mg every other week 
starting at Week 1) in adult patients with uveitis up to 80 weeks with a median exposure of 166.5 days and 
105.0 days in Humira-treated and control-treated patients, respectively, ALT elevations ≥ 3 x ULN 
occurred in 2.4% of Humira-treated patients and 2.4% of control-treated patients.  
 
In the controlled Phase 3 trial of Humira in patients with paediatric ulcerative colitis (N=93) which 
evaluated efficacy and safety of a maintenance dose of 0.6 mg/kg (maximum of 40 mg) every other week 
(N=31) and a maintenance dose of 0.6 mg/kg (maximum of 40 mg) every Week (N=32), following body 
weight adjusted induction dosing of 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2 (N=63), or an induction dose of 2.4 mg/kg (maximum of 160 mg) 



237 

at Week 0, placebo at Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2 (N=30), ALT elevations ≥ 
3 X ULN occurred in 1.1% (1/93) of patients. 
 
Across all indications in clinical trials patients with raised ALT were asymptomatic and in most cases 
elevations were transient and resolved on continued treatment.  However, there have also been post-
marketing reports of liver failure as well as less severe liver disorders that may precede liver failure, such 
as hepatitis including autoimmune hepatitis in patients receiving adalimumab. 
 
Concurrent treatment with azathioprine/6-mercaptopurine 
 
In adult Crohn’s disease studies, higher incidences of malignant and serious infection-related adverse 
events were seen with the combination of Humira and azathioprine/6-mercaptopurine compared with 
Humira alone. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important.  It allows 
continued monitoring of the benefit/risk balance of the medicinal product.  Healthcare professionals are 
asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.  
 
4.9 Overdose 
 
No dose-limiting toxicity was observed during clinical trials. The highest dose level evaluated has been 
multiple intravenous doses of 10 mg/kg, which is approximately 15 times the recommended dose.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunosuppressants, Tumour Necrosis Factor alpha (TNF-α) inhibitors. 
ATC code: L04AB04 
 
Mechanism of action 
 
Adalimumab binds specifically to TNF and neutralises the biological function of TNF by blocking its 
interaction with the p55 and p75 cell surface TNF receptors.   
 
Adalimumab also modulates biological responses that are induced or regulated by TNF, including changes 
in the levels of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, and ICAM-1 
with an IC50 of 0.1-0.2 nM).  
 
Pharmacodynamic effects  
 
After treatment with Humira, a rapid decrease in levels of acute phase reactants of inflammation 
(C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) and serum cytokines (IL-6) was 
observed, compared to baseline in patients with rheumatoid arthritis. Serum levels of matrix 
metalloproteinases (MMP-1 and MMP-3) that produce tissue remodelling responsible for cartilage 
destruction were also decreased after Humira administration. Patients treated with Humira usually 
experienced improvement in haematological signs of chronic inflammation. 
 
A rapid decrease in CRP levels was also observed in patients with polyarticular juvenile idiopathic 
arthritis, Crohn’s disease, ulcerative colitis and hidradenitis suppurativa after treatment with Humira. In 



238 

patients with Crohn’s disease, a reduction of the number of cells expressing inflammatory markers in the 
colon including a significant reduction of expression of TNFα was seen. Endoscopic studies in intestinal 
mucosa have shown evidence of mucosal healing in adalimumab treated patients. 
 
Clinical efficacy and safety 
 
Rheumatoid arthritis 
 
Humira was evaluated in over 3,000 patients in all rheumatoid arthritis clinical trials. The efficacy and 
safety of Humira were assessed in five randomised, double-blind and well-controlled studies. Some 
patients were treated for up to 120 months duration. Injection site pain of Humira 40 mg/0.4 ml was 
assessed in two randomised, active control, single-blind, two-period crossover studies.  
 
RA study I evaluated 271 patients with moderately to severely active rheumatoid arthritis who were 
 18 years old, had failed therapy with at least one disease-modifying, anti rheumatic drug and had 
insufficient efficacy with methotrexate at doses of 12.5 to 25 mg (10 mg if methotrexate-intolerant) every 
week and whose methotrexate dose remained constant at 10 to 25 mg every week. Doses of 20, 40 or 
80 mg of Humira or placebo were given every other week for 24 weeks.  
 
RA study II evaluated 544 patients with moderately to severely active rheumatoid arthritis who were 
 18 years old and had failed therapy with at least one disease-modifying, anti-rheumatic drugs.  Doses of 
20 or 40 mg of Humira were given by subcutaneous injection every other week with placebo on alternative 
weeks or every week for 26 weeks; placebo was given every week for the same duration.  No other 
disease-modifying anti-rheumatic drugs were allowed. 
 
RA study III evaluated 619 patients with moderately to severely active rheumatoid arthritis who were 
 18 years old, and who had an ineffective response to methotrexate at doses of 12.5 to 25 mg or have 
been intolerant to 10 mg of methotrexate every week. There were three groups in this study.  The first 
received placebo injections every week for 52 weeks. The second received 20 mg of Humira every week 
for 52 weeks. The third group received 40 mg of Humira every other week with placebo injections on 
alternate weeks. Upon completion of the first 52 weeks, 457 patients enrolled in an open-label extension 
phase in which 40 mg of Humira/MTX was administered every other week up to 10 years. 
 
RA study IV primarily assessed safety in 636 patients with moderately to severely active rheumatoid 
arthritis who were  18 years old. Patients were permitted to be either disease-modifying, anti-rheumatic 
drug-naïve or to remain on their pre-existing rheumatologic therapy provided that therapy was stable for a 
minimum of 28 days. These therapies include methotrexate, leflunomide, hydroxychloroquine, 
sulfasalazine and/or gold salts. Patients were randomised to 40 mg of Humira or placebo every other week 
for 24 weeks.   
 
RA study V evaluated 799 methotrexate-naïve, adult patients with moderate to severely active early 
rheumatoid arthritis (mean disease duration less than 9 months). This study evaluated the efficacy of 
Humira 40 mg every other week/methotrexate combination therapy, Humira 40 mg every other week 
monotherapy and methotrexate monotherapy in reducing the signs and symptoms and rate of progression 
of joint damage in rheumatoid arthritis for 104 weeks. Upon completion of the first 104 weeks, 497 
patients enrolled in an open-label extension phase in which 40 mg of Humira was administered every 
other week up to 10 years. 
 
RA studies VI and VII each evaluated 60 patients with moderately to severely active rheumatoid arthritis 
who were ≥ 18 years old. Enrolled patients were either current users of Humira 40 mg/0.8 ml and rated 
their average injection site pain as at least 3 cm (on a 0-10 cm VAS) or were biologic-naïve subjects who 
were starting Humira 40 mg/0.8 ml. Patients were randomised to receive a single dose of Humira 



239 

40 mg/0.8 ml or Humira 40 mg/0.4 ml, followed by a single injection of the opposite treatment at their 
next dose.  
 
The primary end point in RA studies I, II and III and the secondary endpoint in RA study IV was the 
percent of patients who achieved an ACR 20 response at Week 24 or 26. The primary endpoint in RA 
study V was the percent of patients who achieved an ACR 50 response at Week 52. RA studies III and V 
had an additional primary endpoint at 52 weeks of retardation of disease progression (as detected by X-ray 
results). RA study III also had a primary endpoint of changes in quality of life. The primary endpoint in 
RA studies VI and VII was injection site pain immediately after injection as measured by a 0-10 cm VAS. 
 
ACR response 
 
The percent of Humira-treated patients achieving ACR 20, 50 and 70 responses was consistent across RA 
studies I, II and III. The results for the 40 mg every other week dose are summarised in Table 5.  
 

Table 5 
ACR Responses in Placebo-Controlled Trials 

(Percent of Patients) 
 

Response RA Study Ia** RA Study IIa** RA Study IIIa** 
 

 Placebo/ 
MTXc 
n=60 

Humirab/ MTXc

n=63 
Placebo 
n=110 

Humirab 
n=113 

Placebo/ 
MTXc 
n=200 

Humirab/ MTXc

n=207 

ACR 20    
 6 months 13.3% 65.1% 19.1% 46.0% 29.5% 63.3%
 12 months NA NA NA NA 24.0% 58.9%
ACR 50    
 6 months 6.7% 52.4% 8.2% 22.1% 9.5% 39.1%
 12 months NA NA NA NA 9.5% 41.5%
ACR 70    
 6 months 3.3% 23.8% 1.8% 12.4% 2.5% 20.8%
 12 months NA NA NA NA 4.5% 23.2%
a RA study I at 24 weeks, RA study II at 26 weeks , and RA study III at 24 and 52 weeks 
b 40 mg Humira administered every other week 
c MTX = methotrexate 
**p < 0.01, Humira versus placebo 

 
In RA studies I-IV, all individual components of the ACR response criteria (number of tender and swollen 
joints, physician and patient assessment of disease activity and pain, disability index (HAQ) scores and 
CRP (mg/dl) values) improved at 24 or 26 weeks compared to placebo. In RA study III, these 
improvements were maintained throughout 52 weeks.  
 
In the open-label extension for RA study III, most patients who were ACR responders maintained 
response when followed for up to 10 years. Of 207 patients who were randomised to Humira 40 mg every 
other week, 114 patients continued on Humira 40 mg every other week for 5 years. Among those, 86 
patients (75.4%) had ACR 20 responses; 72 patients (63.2%) had ACR 50 responses; and 41 patients 
(36%) had ACR 70 responses. Of 207 patients, 81 patients continued on Humira 40 mg every other week 
for 10 years. Among those, 64 patients (79.0%) had ACR 20 responses; 56 patients (69.1%) had ACR 50 
responses; and 43 patients (53.1%) had ACR 70 responses. 
 
In RA study IV, the ACR 20 response of patients treated with Humira plus standard of care was 
statistically significantly better than patients treated with placebo plus standard of care (p < 0.001).   



240 

 
In RA studies I-IV, Humira-treated patients achieved statistically significant ACR 20 and 50 responses 
compared to placebo as early as one to two weeks after initiation of treatment. 
 
In RA study V with early rheumatoid arthritis patients who were methotrexate naïve, combination therapy 
with Humira and methotrexate led to faster and significantly greater ACR responses than methotrexate 
monotherapy and Humira monotherapy at Week 52 and responses were sustained at Week 104 (see Table 
6). 
 

Table 6 
ACR Responses in RA Study V 

(percent of patients) 
 

Response 
MTX 
n=257 

Humira 
n=274 

Humira/MTX 
n=268 

p-valuea p-valueb p-valuec 

ACR 20   
 Week 
52 

62.6% 54.4% 72.8% 0.013 < 0.001 0.043 

 Week 
104 

56.0% 49.3% 69.4% 0.002 < 0.001 0.140 

ACR 50   
 Week 
52 

45.9% 41.2% 61.6% < 0.001 < 0.001 0.317 

 Week 
104 

42.8% 36.9% 59.0% < 0.001 < 0.001 0.162 

ACR 70   
 Week 
52 

27.2% 25.9% 45.5% < 0.001 < 0.001 0.656 

 Week 
104 

28.4% 28.1% 46.6% < 0.001 < 0.001 0.864 

a. p-value is from the pairwise comparison of methotrexate monotherapy and Humira/methotrexate 
combination therapy using the Mann-Whitney U test. 

b. p-value is from the pairwise comparison of Humira monotherapy and Humira/methotrexate 
combination therapy using the Mann-Whitney U test 

c.   p-value is from the pairwise comparison of Humira monotherapy and methotrexate monotherapy 
using the Mann-Whitney U test 

 
In the open-label extension for RA study V, ACR response rates were maintained when followed for up to 
10 years. Of 542 patients who were randomised to Humira 40 mg every other week, 170 patients 
continued on Humira 40 mg every other week for 10 years. Among those, 154 patients (90.6%) had ACR 
20 responses; 127 patients (74.7%) had ACR 50 responses; and 102 patients (60.0%) had ACR 70 
responses. 
 
At Week 52, 42.9% of patients who received Humira/methotrexate combination therapy achieved clinical 
remission (DAS28 (CRP) < 2.6) compared to 20.6% of patients receiving methotrexate monotherapy and 
23.4% of patients receiving Humira monotherapy. Humira/methotrexate combination therapy was 
clinically and statistically superior to methotrexate (p < 0.001) and Humira monotherapy (p < 0.001) in 
achieving a low disease state in patients with recently diagnosed moderate to severe rheumatoid arthritis. 
The response for the two monotherapy arms was similar (p = 0.447).  Of 342 subjects originally 
randomized to Humira monotherapy or Humira/methotrexate combination therapy who entered the open-
label extension study, 171 subjects completed 10 years of Humira treatment. Among those, 109 subjects 
(63.7%) were reported to be in remission at 10 years. 
 



241 

Radiographic response 
 
In RA study III, where Humira treated patients had a mean duration of rheumatoid arthritis of 
approximately 11 years, structural joint damage was assessed radiographically and expressed as change in 
modified Total Sharp Score (TSS) and its components, the erosion score and joint space narrowing score.  
Humira/methotrexate patients demonstrated significantly less radiographic progression than patients 
receiving methotrexate alone at 6 and 12 months (see Table 7). 
 
In the open-label extension of RA Study III, the reduction in rate of progression of structural damage is 
maintained for 8 and 10 years in a subset of patients. At 8 years, 81 of 207 patients originally treated with 
40 mg Humira every other week were evaluated radiographically. Among those, 48 patients showed no 
progression of structural damage defined by a change from baseline in the mTSS of 0.5 or less. At 
10 years, 79 of 207 patients originally treated with 40 mg Humira every other week were evaluated 
radiographically. Among those, 40 patients showed no progression of structural damage defined by a 
change from baseline in the mTSS of 0.5 or less. 
 

Table 7 
 Radiographic Mean Changes Over 12 Months in RA Study III 

 
 Placebo/ 

MTXa 
Humira/MTX 
40 mg every 
other week 

Placebo/MTX-
Humira/MTX (95% 

Confidence 
Intervalb)

p-value 

Total Sharp Score 2.7 0.1 2.6 (1.4, 3.8) < 0.001c 

Erosion score 1.6 0.0 1.6 (0.9, 2.2) < 0.001 
JSNd score 1.0 0.1 0.9 (0.3, 1.4)   0.002 

amethotrexate 
b95% confidence intervals for the differences in change scores between methotrexate and Humira.  
cBased on rank analysis  
dJoint Space Narrowing 
 
In RA study V, structural joint damage was assessed radiographically and expressed as change in modified 
Total Sharp Score (see Table 8). 
 

Table 8 
  Radiographic Mean Changes at Week 52 in RA Study V 

 

 

MTX 
n=257 
(95% 

confidence 
interval) 

Humira 
n=274 
(95% 

confidence 
interval)

Humira/MTX 
n=268 
(95% 

confidence 
interval)

p-valuea p-valueb p-valuec 

Total Sharp 
Score 

5.7 (4.2-7.3) 3.0 (1.7-4.3) 1.3 (0.5-2.1) < 0.001 0.0020 < 0.001 

Erosion score 3.7 (2.7-4.7) 1.7 (1.0-2.4) 0.8 (0.4-1.2) < 0.001 0.0082 < 0.001
JSN score 2.0 (1.2-2.8) 1.3 (0.5-2.1) 0.5 (0-1.0) < 0.001 0.0037 0.151

a p-value is from the pairwise comparison of methotrexate monotherapy and Humira/methotrexate 
combination therapy using the Mann-Whitney U test. 

b p-value is from the pairwise comparison of Humira monotherapy and Humira/methotrexate 
combination therapy using the Mann-Whitney U test  

c p-value is from the pairwise comparison of Humira monotherapy and methotrexate monotherapy 
using the Mann-Whitney U test 

 



242 

Following 52 weeks and 104 weeks of treatment, the percentage of patients without progression (change 
from baseline in modified Total Sharp Score  0.5) was significantly higher with Humira/methotrexate 
combination therapy (63.8% and 61.2% respectively) compared to methotrexate monotherapy (37.4% and 
33.5% respectively, p < 0.001) and Humira monotherapy (50.7%, p < 0.002 and 44.5%, p < 0.001 
respectively). 
 
In the open-label extension of RA study V, the mean change from baseline at Year 10 in the modified 
Total Sharp Score was 10.8, 9.2 and 3.9 in patients originally randomized to methotrexate monotherapy, 
Humira monotherapy and Humira/methotrexate combination therapy, respectively. The corresponding 
proportions of patients with no radiographic progression were 31.3%, 23.7% and 36.7% respectively. 
 
Quality of life and physical function  
 
Health-related quality of life and physical function were assessed using the disability index of the Health 
Assessment Questionnaire (HAQ) in the four original adequate and well-controlled trials, which was a 
pre-specified primary endpoint at Week 52 in RA study III. All doses/schedules of Humira in all four 
studies showed statistically significantly greater improvement in the disability index of the HAQ from 
baseline to Month 6 compared to placebo and in RA study III the same was seen at Week 52. Results from 
the Short Form Health Survey (SF 36) for all doses/schedules of Humira in all four studies support these 
findings, with statistically significant physical component summary (PCS) scores, as well as statistically 
significant pain and vitality domain scores for the 40 mg every other week dose. A statistically significant 
decrease in fatigue as measured by functional assessment of chronic illness therapy (FACIT) scores was 
seen in all three studies in which it was assessed (RA studies I, III, IV). 
 
In RA study III, most subjects who achieved improvement in physical function and continued treatment 
maintained improvement through Week 520 (120 months) of open-label treatment. Improvement in 
quality of life was measured up to Week 156 (36 months) and improvement was maintained through that 
time. 
 
In RA study V, the improvement in the HAQ disability index and the physical component of the SF 36 
showed greater improvement (p < 0.001) for Humira/methotrexate combination therapy versus 
methotrexate monotherapy and Humira monotherapy at Week 52, which was maintained through 
Week 104. Among the 250 subjects who completed the open-label extension study, improvements in 
physical function were maintained through 10 years of treatment. 
 
Injection site pain 
 
For the pooled crossover RA studies VI and VII, a statistically significant difference for injection site pain 
immediately after dosing was observed between Humira 40 mg/0.8 ml and Humira 40 mg/0.4 ml (mean 
VAS of 3.7 cm versus 1.2 cm, scale of 0-10 cm, P < 0.001).  This represented an 84% median reduction in 
injection site pain. 
 
Psoriasis  
 
The safety and efficacy of Humira were studied in adult patients with chronic plaque psoriasis ( 10% 
BSA involvement and Psoriasis Area and Severity Index (PASI)  12 or  10) who were candidates for 
systemic therapy or phototherapy in randomised, double-blind studies. 73% of patients enrolled in 
Psoriasis Studies I and II had received prior systemic therapy or phototherapy.  The safety and efficacy of 
Humira were also studied in adult patients with moderate to severe chronic plaque psoriasis with 
concomitant hand and/or foot psoriasis who were candidates for systemic therapy in a randomised double-
blind study (Psoriasis Study III).   
 



243 

Psoriasis Study I (REVEAL) evaluated 1,212 patients within three treatment periods.  In period A, patients 
received placebo or Humira at an initial dose of 80 mg followed by 40 mg every other week starting one 
week after the initial dose. After 16 weeks of therapy, patients who achieved at least a PASI 75 response 
(PASI score improvement of at least 75% relative to baseline), entered period B and received open-label 
40 mg Humira every other week. Patients who maintained PASI 75 response at Week 33 and were 
originally randomised to active therapy in Period A, were re-randomised in period C to receive 40 mg 
Humira every other week or placebo for an additional 19 weeks. Across all treatment groups, the mean 
baseline PASI score was 18.9 and the baseline Physician’s Global Assessment (PGA) score ranged from 
“moderate” (53% of subjects included) to “severe” (41%) to “very severe” (6%). 
 
Psoriasis Study II (CHAMPION) compared the efficacy and safety of Humira versus methotrexate and 
placebo in 271 patients. Patients received placebo, an initial dose of MTX 7.5 mg and thereafter dose 
increases up to Week 12, with a maximum dose of 25 mg or an initial dose of 80 mg Humira followed by 
40 mg every other week (starting one week after the initial dose) for 16 weeks. There are no data available 
comparing Humira and MTX beyond 16 weeks of therapy. Patients receiving MTX who achieved a 
PASI 50 response at Week 8 and/or 12 did not receive further dose increases. Across all treatment 
groups, the mean baseline PASI score was 19.7 and the baseline PGA score ranged from “mild” (<1%) to 
“moderate” (48%) to “severe” (46%) to “very severe” (6%). 
 
Patients participating in all Phase 2 and Phase 3 psoriasis studies were eligible to enrol into an open-label 
extension trial, where Humira was given for at least an additional 108 weeks. 
 
In Psoriasis Studies I and II, a primary endpoint was the proportion of patients who achieved a PASI 75 
response from baseline at Week 16 (see Tables 9 and 10). 
 

Table 9 
Ps Study I (REVEAL)  - Efficacy Results at 16 Weeks 

 
Placebo 
N=398 
n (%) 

Humira 40 mg eow 
N=814 
n (%) 

     PASI 75a 26 (6.5) 578 (70.9)b 
    PASI 100 3 (0.8) 163 (20.0)b 
    PGA: Clear/minimal 17 (4.3) 506 (62.2)b 
a Percent of patients achieving PASI75 response was calculated as centre-
adjusted rate 
b p < 0.001, Humira vs. Placebo

 
Table 10 

 Ps Study II (CHAMPION) Efficacy Results at 16 Weeks 

 Placebo 
N=53 
n (%) 

MTX 
N=110 
n (%) 

Humira 40 mg eow 
N=108 
n (%) 

     PASI 75 10 (18.9) 39 (35.5) 86 (79.6) a, b 
    PASI 100 1 (1.9) 8 (7.3) 18 (16.7) c, d 
    PGA: 
Clear/minimal 

6 (11.3) 33 (30.0) 79 (73.1) a, b 

a p < 0.001 Humira vs. placebo 
b p < 0.001 Humira vs. methotrexate 
c p < 0.01 Humira vs. placebo 
d p < 0.05 Humira vs. methotrexate

 



244 

In Psoriasis Study I, 28% of patients who were PASI 75 responders and were re-randomised to placebo at 
Week 33 compared to 5% continuing on Humira, p < 0.001, experienced “loss of adequate response” 
(PASI score after Week 33 and on or before Week 52 that resulted in a <PASI 50 response relative to 
baseline with a minimum of a 6-point increase in PASI score relative to Week 33). Of the patients who 
lost adequate response after re-randomisation to placebo who then enrolled into the open-label extension 
trial, 38% (25/66) and 55% (36/66) regained PASI 75 response after 12 and 24 weeks of re-treatment, 
respectively. 
 
A total of 233 PASI 75 responders at Week 16 and Week 33 received continuous Humira therapy for 
52 weeks in Psoriasis Study I, and continued Humira in the open-label extension trial.  PASI 75 and PGA 
of clear or minimal response rates in these patients were 74.7% and 59.0%, respectively, after an 
additional 108 weeks of open-label therapy (total of 160 weeks). In an analysis in which all patients who 
dropped out of the study for adverse events or lack of efficacy, or who dose-escalated, were considered 
non-responders, PASI 75 and PGA of clear or minimal response rates in these patients were 69.6% and 
55.7%, respectively, after an additional 108 weeks of open-label therapy (total of 160 weeks). 
 
A total of 347 stable responders participated in a withdrawal and retreatment evaluation in an open-label 
extension study. During the withdrawal period, symptoms of psoriasis returned over time with a median 
time to relapse (decline to PGA “moderate” or worse) of approximately 5 months. None of these patients 
experienced rebound during the withdrawal period. A total of 76.5% (218/285) of patients who entered the 
retreatment period had a response of PGA “clear” or “minimal” after 16 weeks of retreatment, irrespective 
of whether they relapsed during withdrawal (69.1%[123/178] and 88.8% [95/107] for patients who 
relapsed and who did not relapse during the withdrawal period, respectively).  A similar safety profile was 
observed during retreatment as before withdrawal. 
 
Significant improvements at Week 16 from baseline compared to placebo (Studies I and II) and MTX 
(Study II) were demonstrated in the DLQI (Dermatology Life Quality Index). In Study I, improvements in 
the physical and mental component summary scores of the SF-36 were also significant compared to 
placebo. 
 
In an open-label extension study, for patients who dose escalated from 40 mg every other week to 40 mg 
weekly due to a PASI response below 50%, 26.4% (92/349) and 37.8% (132/349) of patients achieved 
PASI 75 response at Week 12 and 24, respectively. 
 
Psoriasis Study III (REACH) compared the efficacy and safety of Humira versus placebo in 72 patients 
with moderate to severe chronic plaque psoriasis and hand and/or foot psoriasis. Patients received an 
initial dose of 80 mg Humira followed by 40 mg every other week (starting one week after the initial dose) 
or placebo for 16 weeks. At Week 16, a statistically significantly greater proportion of patients who 
received Humira achieved PGA of 'clear' or 'almost clear' for the hands and/or feet compared to patients 
who received placebo (30.6% versus 4.3%, respectively [P = 0.014]). 
 
Psoriasis Study IV compared efficacy and safety of Humira versus placebo in 217 adult patients with 
moderate to severe nail psoriasis. Patients received an initial dose of 80 mg Humira followed by 40 mg 
every other week (starting one week after the initial dose) or placebo for 26 weeks followed by open-label 
Humira treatment for an additional 26 weeks. Nail psoriasis assessments included the Modified Nail 
Psoriasis Severity Index (mNAPSI), the Physician’s Global Assessment of Fingernail Psoriasis (PGA-F) 
and the Nail Psoriasis Severity Index (NAPSI) (see Table 11). Humira demonstrated a treatment benefit in 
nail psoriasis patients with different extents of skin involvement (BSA≥10% (60% of patients) and 
BSA<10% and ≥5% (40% of patients)).     
 



245 

Table 11 
Ps Study IV Efficacy Results at 16, 26 and 52 Weeks 

Endpoint Week 16 
Placebo-Controlled

Week 26 
Placebo-Controlled

Week 52 
Open-label

Placebo 
N=108 

Humira 
40 mg eow 

N=109

Placebo
N=108 

Humira 
40 mg eow 

N=109

Humira 
40 mg eow  

N=80 
≥ mNAPSI 75 (%) 2.9 26.0a 3.4 46.6a 65.0 
PGA-F clear/minimal and 
≥2-grade improvement (%) 

2.9 29.7a 6.9 48.9a 61.3 

Percent Change in Total 
Fingernail NAPSI (%) 

-7.8 -44.2 a -11.5 -56.2a -72.2 

a p<0.001, Humira vs. placebo  
 
Humira treated patients showed statistically significant improvements at Week 26 compared with placebo 
in the DLQI.  
 
Hidradenitis suppurativa 
 
The safety and efficacy of Humira were assessed in randomised, double-blind, placebo-controlled studies 
and an open-label extension study in adult patients with moderate to severe hidradenitis suppurativa (HS) 
who were intolerant, had a contraindication or an inadequate response to at least a 3-month trial of 
systemic antibiotic therapy.  The patients in HS-I and HS-II had Hurley Stage II or III disease with at least 
3 abscesses or inflammatory nodules. 
 
Study HS-I (PIONEER I) evaluated 307 patients with 2 treatment periods.  In Period A, patients received 
placebo or Humira at an initial dose of 160 mg at Week 0, 80 mg at Week 2, and 40 mg every week 
starting at Week 4 to Week 11.  Concomitant antibiotic use was not allowed during the study.  After 
12 weeks of therapy, patients who had received Humira in Period A were re-randomised in Period B to 1 
of 3 treatment groups (Humira 40 mg every week, Humira 40 mg every other week, or placebo from Week 
12 to Week 35).  Patients who had been randomised to placebo in Period A were assigned to receive 
Humira 40 mg every week in Period B. 
 
Study HS-II (PIONEER II) evaluated 326 patients with 2 treatment periods.  In Period A, patients received 
placebo or Humira at an initial dose of 160 mg at Week 0 and 80 mg at Week 2 and 40 mg every week 
starting at Week 4 to Week 11.  19.3% of patients had continued baseline oral antibiotic therapy during the 
study.  After 12 weeks of therapy, patients who had received Humira in Period A were re-randomised in 
Period B to 1 of 3 treatment groups (Humira 40 mg every week, Humira 40 mg every other week, or 
placebo from Week 12 to Week 35).  Patients who had been randomised to placebo in Period A were 
assigned to receive placebo in Period B. 
 
Patients participating in Studies HS-I and HS-II were eligible to enrol into an open-label extension study 
in which Humira 40mg was administered every week. Mean exposure in all adalimumab population was 
762 days.  Throughout all 3 studies patients used topical antiseptic wash daily. 
 
Clinical Response 
 
Reduction of inflammatory lesions and prevention of worsening of abscesses and draining fistulas was 
assessed using Hidradenitis Suppurativa Clinical Response (HiSCR; at least a 50% reduction in total 
abscess and inflammatory nodule count with no increase in abscess count and no increase in draining 
fistula count relative to Baseline).  Reduction in HS-related skin pain was assessed using a Numeric 
Rating Scale in patients who entered the study with an initial baseline score of 3 or greater on a 11 point 
scale.  



246 

 
At Week 12, a significantly higher proportion of patients treated with Humira versus placebo achieved 
HiSCR.   At Week 12, a significantly higher proportion of patients in Study HS-II experienced a clinically 
relevant decrease in HS-related skin pain (see Table 12).  Patients treated with Humira had significantly 
reduced risk of disease flare during the initial 12 weeks of treatment. 
 

Table 12:  Efficacy Results at 12 Weeks, HS Studies I and II 

 

 

HS Study I HS Study II 

Placebo
Humira 40 mg 

Weekly Placebo  
Humira 40 mg 

Weekly 

Hidradenitis Suppurativa 
Clinical Response (HiSCR)a   

N = 154 
40 (26.0%) 

N = 153 
64 (41.8%) * 

N=163 
45 (27.6%) 

N=163 
96 (58.9%) *** 

≥30% Reduction in Skin 
Painb 

N = 109 
27 (24.8%)

N = 122 
34 (27.9%)

N=111 
23 (20.7%) 

N=105 
48 (45.7%) ***

* P < 0.05, ***P < 0.001, Humira versus placebo  
a Among all randomised patients. 
b Among patients with baseline HS-related skin pain assessment ≥ 3, based on Numeric Rating 

Scale 0 – 10; 0 = no skin pain, 10 = skin pain as bad as you can imagine.
 
Treatment with Humira 40 mg every week significantly reduced the risk of worsening of abscesses and 
draining fistulas.  Approximately twice the proportion of patients in the placebo group in the first 12 
weeks of Studies HS-I and HS-II, compared with those in the Humira group experienced worsening of 
abscesses (23.0% vs 11.4%, respectively) and draining fistulas (30.0% vs 13.9%, respectively). 
 
Greater improvements at Week 12 from baseline compared to placebo were demonstrated in skin-specific 
health-related quality of life, as measured by the Dermatology Life Quality Index (DLQI; Studies HS-I 
and HS-II), patient global satisfaction with medication treatment as measured by the Treatment 
Satisfaction Questionnaire - medication (TSQM; Studies HS-I and HS-II), and physical health as 
measured by the physical component summary score of the SF-36 (Study HS-I). 
 
In patients with at least a partial response to Humira 40 mg weekly at Week 12, the HiSCR rate at Week 
36 was higher in patients who continued weekly Humira than in patients in whom dosing frequency was 
reduced to every other week, or in whom treatment was withdrawn (see Table 13). 
 

Table 13:  Proportion of Patientsa Achieving HiSCRb at Weeks 24 and 36 After 
Treatment Reassignment from Weekly Humira at Week 12 

 

Placebo 
(treatment 

withdrawal) 
N = 73 

Humira 40 mg 
every other week 

N = 70 

Humira 40 mg 
weekly 
N = 70 

Week 24 24 (32.9%) 36 (51.4%) 40 (57.1%) 

Week 36 22 (30.1%) 28 (40.0%) 39 (55.7%) 
a Patients with at least a partial response to Humira 40 mg weekly after 12 

weeks of treatment. 
b Patients meeting protocol-specified criteria for loss of response or no 

improvement were required to discontinue from the studies and were 
counted as nonresponders.

 



247 

Among patients who were at least partial responders at Week 12, and who received continuous weekly 
Humira therapy, the HiSCR rate at Week 48 was 68.3% and at Week 96 was 65.1%. Longer term 
treatment with Humira 40 mg weekly for 96 weeks identified no new safety findings. 
 
Among patients whose Humira treatment was withdrawn at Week 12 in Studies HS-I and HS-II, the 
HiSCR rate 12 weeks after re-introduction of Humira 40 mg weekly returned to levels similar to that 
observed before withdrawal (56.0 %). 
 
Crohn’s disease 
 
The safety and efficacy of Humira were assessed in over 1500 patients with moderately to severely active 
Crohn’s disease (Crohn’s Disease Activity Index (CDAI)  220 and  450) in randomised, double-blind, 
placebo-controlled studies. Concomitant stable doses of aminosalicylates, corticosteroids, and/or 
immunomodulatory agents were permitted and 80% of patients continued to receive at least one of these 
medications.  
 
Induction of clinical remission (defined as CDAI < 150) was evaluated in two studies, CD Study I 
(CLASSIC I) and CD Study II (GAIN). In CD Study I, 299 TNF-antagonist naive patients were 
randomised to one of four treatment groups; placebo at Weeks 0 and 2, 160 mg Humira at Week 0 and 
80 mg at Week 2, 80 mg at Week 0 and 40 mg at Week 2, and 40 mg at Week 0 and 20 mg at Week 2. In 
CD Study II, 325 patients who had lost response or were intolerant to infliximab were randomised to 
receive either 160 mg Humira at Week 0 and 80 mg at Week 2 or placebo at Weeks 0 and 2. The primary 
non-responders were excluded from the studies and therefore these patients were not further evaluated. 
 
Maintenance of clinical remission was evaluated in CD study III (CHARM).  In CD Study III, 854 patients 
received open-label 80 mg at Week 0 and 40 mg at Week 2.  At Week 4 patients were randomised to 
40 mg every other week, 40 mg every week, or placebo with a total study duration of 56 weeks. Patients in 
clinical response (decrease in CDAI ≥ 70) at Week 4 were stratified and analysed separately from those 
not in clinical response at Week 4.  Corticosteroid taper was permitted after Week 8.  
 
CD study I and CD study II induction of remission and response rates are presented in Table 14. 
 

Table 14 
Induction of Clinical Remission and Response 

(Percent of Patients) 

 CD Study I: Infliximab Naive 
Patients 

CD Study II: Infliximab 
Experienced Patients 

 Placebo 
N=74 

Humira 
80/40 mg 

N = 75 

Humira  
160/80 mg 

N=76 

Placebo 
N=166 

Humira  
160/80 mg 

N=159 

Week 4      

Clinical remission 12% 24% 36%* 7% 21%* 

Clinical response (CR-
100) 

24% 37% 49%** 25% 38%** 

All p-values are pairwise comparisons of proportions for Humira versus placebo 
* p < 0.001 
** p < 0.01 

 
Similar remission rates were observed for the 160/80 mg and 80/40 mg induction regimens by Week 8 and 
adverse events were more frequently noted in the 160/80 mg group. 



248 

 
In CD Study III, at Week 4, 58% (499/854) of patients were in clinical response and were assessed in the 
primary analysis. Of those in clinical response at Week 4, 48% had been previously exposed to other TNF-
antagonists. Maintenance of remission and response rates are presented in Table 15.  Clinical remission 
results remained relatively constant irrespective of previous TNF-antagonist exposure. 
 
Disease-related hospitalisations and surgeries were statistically significantly reduced with adalimumab 
compared with placebo at Week 56. 
 

Table 15 
Maintenance of Clinical Remission and Response 

(Percent of Patients) 

 Placebo 40 mg Humira 
every other week 

40 mg Humira
every week 

Week 26 N=170 N=172 N=157 

Clinical remission 17% 40%* 47%* 

Clinical response (CR-100) 27% 52%* 52%* 

Patients in steroid-free remission  
for >=90 daysa 

3% (2/66) 19% (11/58)** 15% (11/74)** 

Week 56 N=170 N=172 N=157 

Clinical remission 12% 36%* 41%* 

Clinical response (CR-100) 17% 41%* 48%* 

Patients in steroid-free remission  
for > = 90 daysa 

5% (3/66) 29% (17/58)* 20% (15/74)** 

* p < 0.001 for Humira versus placebo pairwise comparisons of proportions 
** p < 0.02 for Humira versus placebo pairwise comparisons of proportions 
a Of those receiving corticosteroids at baseline 

 
Among patients who were not in response at Week 4, 43% of Humira maintenance patients responded by 
Week 12 compared to 30% of placebo maintenance patients. These results suggest that some patients who 
have not responded by Week 4 benefit from continued maintenance therapy through Week 12.  Therapy 
continued beyond 12 weeks did not result in significantly more responses (see section 4.2).   
 
117/276 patients from CD study I and 272/777 patients from CD studies II and III were followed through 
at least 3 years of open-label adalimumab therapy.  88 and 189 patients, respectively, continued to be in 
clinical remission.  Clinical response (CR-100) was maintained in 102 and 233 patients, respectively. 
 
Quality of life 
 
In CD Study I and CD Study II, statistically significant improvement in the disease-specific inflammatory 
bowel disease questionnaire (IBDQ) total score was achieved at Week 4 in patients randomised to Humira 
80/40 mg and 160/80 mg compared to placebo and was seen at Weeks 26 and 56 in CD Study III as well 
among the adalimumab treatment groups compared to the placebo group. 
 
Ulcerative colitis 
 
The safety and efficacy of multiple doses of Humira were assessed in adult patients with moderately to 
severely active ulcerative colitis (Mayo score 6 to 12 with endoscopy subscore of 2 to 3) in randomised, 
double-blind, placebo-controlled studies.  
 



249 

In study UC-I, 390 TNF-antagonist naïve patients were randomised to receive either placebo at Weeks 0 
and 2, 160 mg Humira at Week 0 followed by 80 mg at Week 2, or 80 mg Humira at Week 0 followed by 
40 mg at Week 2.  After Week 2, patients in both adalimumab arms received 40 mg eow.  Clinical 
remission (defined as Mayo score ≤ 2 with no subscore > 1) was assessed at Week 8.  
 
In study UC-II, 248 patients received 160 mg of Humira at Week 0, 80 mg at Week 2 and 40 mg eow 
thereafter, and 246 patients received placebo. Clinical results were assessed for induction of remission at 
Week 8 and for maintenance of remission at Week 52.  
 
Patients induced with 160/80 mg Humira achieved clinical remission versus placebo at Week 8 in 
statistically significantly greater percentages in study UC-I (18% vs. 9% respectively, p=0.031) and study 
UC-II (17% vs. 9% respectively, p=0.019). In study UC-II, among those treated with Humira who were in 
remission at Week 8, 21/41 (51%) were in remission at Week 52. 
 
Results from the overall UC-II study population are shown in Table 16. 
 

Table 16 
Response, Remission and Mucosal Healing in Study UC-II 

(Percent of Patients) 
 Placebo

 
Humira 40 mg  

eow 

Week 52 N=246 N=248 
  Clinical Response  18%   30%* 

  Clinical Remission 9%   17%* 
  Mucosal Healing  15%   25%* 
  Steroid-free remission for ≥ 90 days a  6%  

(N=140) 
     13% * 
(N=150) 

Week 8 and 52 
  Sustained Response  12%   24%** 
  Sustained Remission  4%   8%* 
  Sustained Mucosal Healing  11%  19%* 
Clinical remission is Mayo score  ≤ 2 with no subscore > 1; 
Clinical response is decrease from baseline in Mayo score ≥ 3 points and ≥ 30% plus a 
decrease in the rectal bleeding subscore [RBS] ≥ 1 or an absolute RBS of 0 or 1; 
*p < 0.05 for Humira vs. placebo pairwise comparison of proportions  
**p < 0.001 for Humira vs. placebo pairwise comparison of proportions 
a   Of those receiving corticosteroids at baseline 
 
Of those patients who had a response at Week 8, 47% were in response, 29% were in remission, 41% had 
mucosal healing, and 20% were in steroid-free remission for ≥ 90 days at Week 52. 
 
Approximately 40% of patients in study UC-II had failed prior anti-TNF treatment with infliximab. The 
efficacy of adalimumab in those patients was reduced compared to that in anti-TNF naïve patients.  
Among patients who had failed prior anti-TNF treatment, Week 52 remission was achieved by 3% on 
placebo and 10% on adalimumab. 
 
Patients from studies UC-I and UC-II had the option to roll over into an open-label long-term extension 
study (UC III). Following 3 years of adalimumab therapy, 75% (301/402) continued to be in clinical 
remission per partial Mayo score.  



250 

 
Hospitalisation rates 
 
During 52 weeks of studies UC-I and UC-II, lower rates of all-cause hospitalisations and UC-related 
hospitalisations were observed for the adalimumab-treated arm compared to the placebo arm. The number 
of all cause hospitalisations in the adalimumab treatment group was 0.18 per patient year vs. 0.26 per 
patient year in the placebo group and the corresponding figures for UC-related hospitalisations were 0.12 
per patient year vs. 0.22 per patient year. 
 
Quality of life 
 
In study UC-II, treatment with adalimumab resulted in improvements in the Inflammatory Bowel Disease 
Questionnaire (IBDQ) score.  
 
Uveitis 
 
The safety and efficacy of Humira were assessed in adult patients with non-infectious intermediate, 
posterior, and panuveitis, excluding patients with isolated anterior uveitis, in two randomised, double-
masked, placebo-controlled studies (UV I and II). Patients received placebo or Humira at an initial dose of 
80 mg followed by 40 mg every other week starting one week after the initial dose. Concomitant stable 
doses of one non-biologic immunosuppressant were permitted.  
 
Study UV I evaluated 217 patients with active uveitis despite treatment with corticosteroids (oral 
prednisone at a dose of 10 to 60 mg/day). All patients received a 2-week standardised dose of prednisone 
60 mg/day at study entry followed by a mandatory taper schedule, with complete corticosteroid 
discontinuation by Week 15.  
 
Study UV II evaluated 226 patients with inactive uveitis requiring chronic corticosteroid treatment (oral 
prednisone 10 to 35 mg/day) at baseline to control their disease. Patients subsequently underwent a 
mandatory taper schedule, with complete corticosteroid discontinuation by Week 19.  
 
The primary efficacy endpoint in both studies was ´time to treatment failure´. Treatment failure was 
defined by a multi-component outcome based on inflammatory chorioretinal and/or inflammatory retinal 
vascular lesions, anterior chamber (AC) cell grade, vitreous haze (VH) grade and best corrected visual 
acuity (BCVA).  
 
Patients who completed Studies UV I and UV II were eligible to enroll in an uncontrolled long-term 
extension study with an originally planned duration of 78 weeks. Patients were allowed to continue on 
study medication beyond Week 78 until they had access to Humira. 
 
Clinical Response 
 
Results from both studies demonstrated statistically significant reduction of the risk of treatment failure in 
patients treated with Humira versus patients receiving placebo (See Table 17). Both studies demonstrated 
an early and sustained effect of Humira on the treatment failure rate versus placebo (see Figure 1).  
 



251 

Table 17 
Time to Treatment Failure in Studies UV I and UV II 

 
Analysis 
 Treatment 

N Failure 
N (%) 

Median Time to 
Failure (months) 

HRa CI 95% 
for HRa 

P Value b 

Time to Treatment Failure At or After Week 6 in Study UV I   
Primary analysis (ITT)   
 Placebo 107 84 (78.5) 3.0 -- -- -- 
 Adalimumab 110 60 (54.5) 5.6 0.50 0.36, 0.70  < 0.001
Time to Treatment Failure At or After Week 2 in Study UV II 
Primary analysis (ITT)   
 Placebo 111 61 (55.0) 8.3 -- -- -- 
 Adalimumab 115 45 (39.1) NEc 0.57 0.39, 0.84 0.004 

Note:  Treatment failure at or after Week 6 (Study UV I), or at or after Week 2 (Study UV II), was 
counted as event. Drop outs due to reasons other than treatment failure were censored at the time of 
dropping out. 
a HR of adalimumab vs placebo from proportional hazards regression with treatment as factor. 
b 2-sided P value from log rank test. 
c NE = not estimable. Fewer than half of at-risk subjects had an event.  
 
Figure 1: Kaplan-Meier Curves Summarizing Time to Treatment Failure on or after Week 6 (Study 

UV I) or Week 2 (Study UV II) 
 

T
R

E
A

T
M

E
N

T
 F

A
IL

U
R

E
 R

A
T

E
 (

%
) 

 TIME (MONTHS) 
 Study UV I                        Treatment Placebo Adalimumab 



252 

T
R

E
A

T
M

E
N

T
 F

A
IL

U
R

E
 R

A
T

E
 (

%
) 

 TIME (MONTHS)
 Study UV II                       Treatment Placebo Adalimumab 

Note: P# = Placebo (Number of Events/Number at Risk); A# = HUMIRA (Number of 
Events/Number at Risk). 

 
In Study UV I statistically significant differences in favour of adalimumab versus placebo were observed 
for each component of treatment failure.  In Study UV II, statistically significant differences were 
observed for visual acuity only, but the other components were numerically in favour of adalimumab. 
 
Of the 424 subjects included in the uncontrolled long-term extension of Studies UV I and UV II, 60 
subjects were regarded ineligible (e.g. due to deviations or due to complications secondary to diabetic 
retinopathy, due to cataract surgery or vitrectomy) and were excluded from the primary analysis of 
efficacy. Of the 364 remaining patients, 269 evaluable patients (74%) reached 78 weeks of open-label 
adalimumab treatment. Based on the observed data approach, 216 (80.3%) were in quiescence (no active 
inflammatory lesions, AC cell grade ≤ 0.5+, VH grade ≤ 0.5+) with a concomitant steroid dose ≤ 7.5 mg 
per day, and 178 (66.2%) were in steroid-free quiescence. BCVA was either improved or maintained (< 5 
letters deterioration) in 88.6% of the eyes at week 78. Data beyond Week 78 were generally consistent 
with these results but the number of enrolled subjects declined after this time. Overall, among the patients 
who discontinued the study, 18% discontinued due to adverse events, and 8% due to insufficient response 
to adalimumab treatment. 
 
Quality of Life 
 
Patient reported outcomes regarding vision-related functioning were measured in both clinical studies, 
using the NEI VFQ-25. Humira was numerically favoured for the majority of subscores with statistically 
significant mean differences for general vision, ocular pain, near vision, mental health, and total score in 
Study UV I, and for general vision and mental health in Study UV II. Vision related effects were not 
numerically in favour of Humira for colour vision in Study UVI and for colour vision, peripheral vision 
and near vision in Study UV II. 
 
Immunogenicity 
 
Formation of anti-adalimumab antibodies is associated with increased clearance and reduced efficacy of 
adalimumab. There is no apparent correlation between the presence of anti-adalimumab antibodies and the 
occurrence of adverse events. 
 



253 

Patients in rheumatoid arthritis studies I, II and III were tested at multiple time points for anti-adalimumab 
antibodies during the 6 to 12 month period. In the pivotal trials, anti-adalimumab antibodies were 
identified in 5.5% (58/1053) of patients treated with adalimumab, compared to 0.5% (2/370) on placebo.  
In patients not given concomitant methotrexate, the incidence was 12.4%, compared to 0.6% when 
adalimumab was used as add-on to methotrexate.   
 
In patients with Crohn’s disease, anti-adalimumab antibodies were identified in 7/269 subjects (2.6%) and 
in 19/487 subjects (3.9%) with ulcerative colitis. 
 
In adult patients with psoriasis, anti-adalimumab antibodies were identified in 77/920 subjects (8.4%) 
treated with adalimumab monotherapy. 
 
In adult plaque psoriasis patients on long term adalimumab monotherapy who participated in a withdrawal 
and retreatment study, the rate of antibodies to adalimumab after retreatment (11 of 482 subjects, 2.3%) 
was similar to the rate observed prior to withdrawal (11 of 590 subjects, 1.9%). 
 
In patients with moderate to severe hidradenitis suppurativa, anti-adalimumab antibodies were identified 
in 10/99 subjects (10.1%) treated with adalimumab. 
 
In patients with moderately to severely active paediatric Crohn’s disease, the rate of anti-adalimumab 
antibody development in patients receiving adalimumab was 3.3%.  
 
In adult patients with non-infectious uveitis, anti-adalimumab antibodies were identified in 4.8% (12/249) 
of patients treated with adalimumab. 
 
In patients with moderately to severely active paediatric ulcerative colitis, the rate of anti-adalimumab 
antibody development in patients receiving adalimumab was 3%. 
 
Because immunogenicity analyses are product-specific, comparison of antibody rates with those from 
other products is not appropriate. 
 
Paediatric population 
 
Adolescent hidradenitis suppurativa 
 
There are no clinical trials with Humira in adolescent patients with HS.  Efficacy of adalimumab for the 
treatment of adolescent patients with HS is predicted based on the demonstrated efficacy and exposure-
response relationship in adult HS patients and the likelihood that the disease course, pathophysiology, and 
drug effects are substantially similar to that of adults at the same exposure levels. Safety of the 
recommended adalimumab dose in the adolescent HS population is based on cross-indication safety 
profile of adalimumab in both adults and paediatric patients at similar or more frequent doses (see section 
5.2). 
 
Paediatric Crohn’s disease  
 
Humira was assessed in a multicentre, randomised, double-blind clinical trial designed to evaluate the 
efficacy and safety of induction and maintenance treatment with doses dependent on body weight (< 40 kg 
or ≥ 40 kg) in 192 paediatric subjects between the ages of 6 and 17 (inclusive) years, with moderate to 
severe Crohn´s disease (CD) defined as Paediatric Crohn's Disease Activity Index (PCDAI) score > 30.  
Subjects had to have failed conventional therapy (including a corticosteroid and/or an immunomodulator) 
for CD. Subjects may also have previously lost response or been intolerant to infliximab.  
 



254 

All subjects received open-label induction therapy at a dose based on their Baseline body weight: 160 mg 
at Week 0 and 80 mg at Week 2 for subjects ≥ 40 kg, and 80 mg and 40 mg, respectively, for subjects 
< 40 kg. 
 
At Week 4, subjects were randomised 1:1 based on their body weight at the time to either the Low Dose or 
Standard Dose maintenance regimens as shown in Table 18. 
 

Table 18 
Maintenance regimen

Patient 
Weight 

Low dose Standard 
dose 

< 40 kg 10 mg eow 20 mg eow
≥ 40 kg 20 mg eow 40 mg eow

 
Efficacy results 
 
The primary endpoint of the study was clinical remission at Week 26, defined as PCDAI score  10. 
 
Clinical remission and clinical response (defined as reduction in PCDAI score of at least 15 points from 
Baseline) rates are presented in Table 19. Rates of discontinuation of corticosteroids or 
immunomodulators are presented in Table 20. 
 

Table 19 
Paediatric CD Study 

PCDAI Clinical Remission and Response 
 Standard Dose

40/20 mg eow 
N = 93 

Low Dose 
20/10 mg eow 

N = 95 

P value* 

Week 26    
   Clinical remission 38.7% 28.4% 0.075 
   Clinical response  59.1% 48.4% 0.073 
Week 52    
   Clinical remission 33.3% 23.2% 0.100 
   Clinical response 41.9% 28.4% 0.038 
* p value for Standard Dose versus Low Dose comparison.

 



255 

Table 20 
Paediatric CD Study 

Discontinuation of Corticosteroids or Immunomodulators and Fistula Remission 
 Standard Dose

40/20 mg eow  
Low Dose 

20/10 mg eow  
P value1 

Discontinued corticosteroids N= 33 N=38  
Week 26 84.8% 65.8% 0.066 
Week 52 69.7% 60.5% 0.420 
Discontinuation of Immunomodulators2 N=60 N=57  
Week 52 30.0% 29.8% 0.983 
Fistula remission3 N=15 N=21  
Week 26 46.7% 38.1% 0.608 
Week 52 40.0% 23.8% 0.303 
1  p value for Standard Dose versus Low Dose comparison. 
2  Immunosuppressant therapy could only be discontinued at or after Week 26 at the 
investigator's discretion if the subject met the clinical response criterion  
3 defined as a closure of all fistulas that were draining at Baseline for at least 2 consecutive 
post-Baseline visits

 
Statistically significant increases (improvement) from Baseline to Week 26 and 52 in Body Mass Index 
and height velocity were observed for both treatment groups. 
 
Statistically and clinically significant improvements from Baseline were also observed in both treatment 
groups for quality of life parameters (including IMPACT III). 
 
One hundred patients (n=100) from the Paediatric CD Study continued in an open-label long-term 
extension study.  After 5 years of adalimumab therapy, 74.0% (37/50) of the 50 patients remaining in the 
study continued to be in clinical remission, and 92.0% (46/50) of patients continued to be in clinical 
response per PCDAI. 
 
Paediatric ulcerative colitis 
 
The safety and efficacy of Humira was assessed in a multicenter, randomized, double-blind, trial in 93 
paediatric patients from 5 to 17 years of age with moderate to severe ulcerative colitis (Mayo score 6 to 12 
with endoscopy subscore of 2 to 3 points, confirmed by centrally read endoscopy) who had an inadequate 
response or intolerance to conventional therapy. Approximately 16% of patients in the study had failed 
prior anti-TNF treatment. Patients who received corticosteroids at enrollment were allowed to taper their 
corticosteroid therapy after Week 4. 
 
In the induction period of the study, 77 patients were randomized 3:2 to receive double-blind treatment 
with Humira at an induction dose of 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2; or an induction dose of 2.4 mg/kg (maximum of 160 mg) at Week 
0, placebo at Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2. Both groups received 0.6 mg/kg 
(maximum of 40 mg) at Week 4 and Week 6. Following an amendment to the study design, the remaining 
16 patients who enrolled in the induction period received open-label treatment with Humira at the 
induction dose of 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 mg/kg (maximum of 
80 mg) at Week 2.  
 
At Week 8, 62 patients who demonstrated clinical response per Partial Mayo Score (PMS; defined as a 
decrease in PMS ≥ 2 points and ≥ 30% from Baseline) were randomized equally to receive double-blind 
maintenance treatment with Humira at a dose of 0.6 mg/kg (maximum of 40 mg) every week (ew), or a 
maintenance dose of 0.6 mg/kg (maximum of 40 mg) every other week (eow). Prior to an amendment to 



256 

the study design, 12 additional patients who demonstrated clinical response per PMS were randomized to 
receive placebo but were not included in the confirmatory analysis of efficacy. 
 
Disease flare was defined as an increase in PMS of at least 3 points (for patients with PMS of 0 to 2 at 
Week 8), at least 2 points (for patients with PMS of 3 to 4 at Week 8), or at least 1 point (for patients with 
PMS of 5 to 6 at Week 8).  
 
Patients who met criteria for disease flare at or after Week 12 were randomized to receive a re-induction 
dose of 2.4 mg/kg (maximum of 160 mg) or a dose of 0.6 mg/kg (maximum of 40 mg) and continued to 
receive their respective maintenance dose regimen afterwards.  
 

Efficacy Results 

 

The co-primary endpoints of the study were clinical remission per PMS (defined as PMS ≤ 2 and no 
individual subscore > 1) at Week 8, and clinical remission per FMS (Full Mayo Score) (defined as a Mayo 
Score ≤ 2 and no individual subscore > 1) at Week 52 in patients who achieved clinical response per PMS 
at Week 8. 
 
Clinical remission rates per PMS at Week 8 for patients in each of the Humira double-
blind induction groups are presented in Table 21.  
 

Table 21: Clinical Remission per PMS at 8 Weeks  

 

Humiraa 
Maximum of 160 mg at Week 

0 / Placebo at Week 1  
N=30 

Humirab, c  
Maximum of 160 mg at Week 

0 and Week 1  
N=47 

Clinical remission 13/30 (43.3%) 28/47 (59.6%) 

a Humira 2.4 mg/kg (maximum of 160 mg) at Week 0, placebo at Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2  
b Humira 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2  
c Not including open-label Induction dose of Humira 2.4 mg/kg (maximum of 160 mg) at 
Week 0 and Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2 
Note 1: Both induction groups received 0.6 mg/kg (maximum of 40 mg) at Week 4 and 
Week 6  
Note 2: Patients with missing values at Week 8 were considered as not having met the 
endpoint  

 
At Week 52, clinical remission per FMS in Week 8 responders, clinical response per FMS (defined as a 
decrease in Mayo Score ≥ 3 points and ≥ 30% from Baseline) in Week 8 responders, mucosal healing per 
FMS (defined as an Mayo endoscopy score ≤ 1) in Week 8 responders, clinical remission per FMS in 
Week 8 remitters, and the proportion of subjects in corticosteroid-free remission per FMS in Week 8 
responders were assessed in patients who received Humira at the double-blind maximum 40 mg eow (0.6 
mg/kg) and maximum 40 mg ew (0.6 mg/kg) maintenance doses (Table 22). 
 
 
 



257 

Table 22: Efficacy Results at 52 Weeks   
Humiraa   

Maximum of 40 mg eow 
N=31 

Humirab   
Maximum of 40 mg ew  

N=31 

Clinical remission in Week 
8 PMS responders  

9/31 (29.0%)  14/31 (45.2%) 

Clinical response in Week 8 
PMS responders  

19/31 (61.3%)  21/31 (67.7%)  

Mucosal healing in 
Week 8 PMS responders  

12/31 (38.7%)  16/31 (51.6%)  

Clinical remission in Week 
8 PMS remitters  

9/21 (42.9%)  10/22 (45.5%)  

Corticosteroid-free 
remission in Week 8 
PMS respondersc  

4/13 (30.8%)  5/16 (31.3%)  

a Humira 0.6 mg/kg (maximum of 40 mg) every other week  
b Humira 0.6 mg/kg (maximum of 40 mg) every week  
c In patients receiving concomitant corticosteroids at baseline  
Note: Patients with missing values at Week 52 or who were randomized to receive 
re-induction or maintenance treatment were considered non-responders for Week 52 
endpoints  

 
Additional exploratory efficacy endpoints included clinical response per the Paediatric Ulcerative Colitis 
Activity Index (PUCAI) (defined as a decrease in PUCAI ≥ 20 points from Baseline) and clinical 
remission per PUCAI (defined as PUCAI < 10) at Week 8 and Week 52 (Table 23).  
 



258 

Table 23: Exploratory Endpoints Results per PUCAI 
 Week 8 

Humiraa

Maximum of 160 mg at 
Week 0 / Placebo at Week 1 

N=30 

Humirab,c 

Maximum of 160 mg at 
Week 0 and Week 1 

N=47 
Clinical remission per PUCAI 10/30 (33.3%) 22/47 (46.8%) 
Clinical response per PUCAI 15/30 (50.0%) 32/47 (68.1%) 
 Week 52 

Humirad

Maximum of 40 mg eow 
N=31

Humirae 

Maximum of 40 mg ew 
N=31 

Clinical remission per PUCAI 
in Week 8 PMS responders 

14/31 (45.2%) 18/31 (58.1%) 

Clinical response per PUCAI 
in Week 8 PMS responders 

18/31 (58.1%) 16/31 (51.6%) 

a Humira 2.4 mg/kg (maximum of 160 mg) at Week 0, placebo at Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2  
b  Humira 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 
mg/kg (maximum of 80 mg) at Week 2  
c Not including open-label Induction dose of Humira 2.4 mg/kg (maximum of 160 mg) at 
Week 0 and Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2 
d Humira 0.6 mg/kg (maximum of 40 mg) every other week 
e Humira 0.6 mg/kg (maximum of 40 mg) every week 
Note 1: Both induction groups received 0.6 mg/kg (maximum of 40 mg) at Week 4 and 
Week 6  
Note 2: Patients with missing values at Week 8 were considered as not having met the 
endpoints  
Note 3: Patients with missing values at Week 52 or who were randomized to receive re-
induction or maintenance treatment were considered non-responders for Week 52 
endpoints 

 
Of the Humira-treated patients who received re-induction treatment during the maintenance period, 2/6 
(33%) achieved clinical response per FMS at Week 52. 
 
Quality of life 
 
Clinically meaningful improvements from Baseline were observed in IMPACT III and the caregiver Work 
Productivity and Activity Impairment (WPAI) scores for the groups treated with Humira.  
 
Clinically meaningful increases (improvement) from Baseline in height velocity were observed for the 
groups treated with adalimumab, and clinically meaningful increases (improvement) from Baseline in 
Body Mass Index were observed for subjects on the high maintenance dose of maximum 40 mg (0.6 
mg/kg) ew.  
 
Paediatric Uveitis  
 
The safety and efficacy of Humira was assessed in a randomized, double-masked, controlled study of 90 
paediatric patients from 2 to < 18 years of age with active JIA-associated noninfectious anterior uveitis 
who were refractory to at least 12 weeks of methotrexate treatment.  Patients received either placebo or 
20 mg adalimumab (if < 30 kg) or 40 mg adalimumab (if ≥ 30 kg) every other week in combination with 
their baseline dose of methotrexate.  



259 

 
The primary endpoint was ‘time to treatment failure’. The criteria determining treatment failure were 
worsening or sustained non-improvement in ocular inflammation, partial improvement with development 
of sustained ocular co-morbidities or worsening of ocular co-morbidities, non-permitted use of 
concomitant medications, and suspension of treatment for an extended period of time. 
 
Clinical Response 
 
Adalimumab significantly delayed the time to treatment failure, as compared to placebo (See Figure 2, 
P < 0.0001 from log rank test).The median time to treatment failure was 24.1 weeks for subjects treated 
with placebo, whereas the median time to treatment failure was not estimable for subjects treated with 
adalimumab because less than one-half of these subjects experienced treatment failure.  Adalimumab 
significantly decreased the risk of treatment failure by 75% relative to placebo, as shown by the hazard 
ratio (HR = 0.25 [95% CI:  0.12, 0.49]). 
 

Figure 2: Kaplan-Meier Curves Summarizing Time to Treatment Failure in the Paediatric Uveitis 

Study 

 

P
R

O
B

A
B

IL
IT

Y
 O

F
 F

A
IL

IN
G

 T
R

E
A

T
M

E
N

T
 

 TIME (WEEKS) 
 Treatment Placebo  Adalimumab 
 Note: P = Placebo (Number at Risk); H = HUMIRA (Number at Risk).

 
 
 



260 

5.2 Pharmacokinetic properties 
 
Absorption and distribution 
 
After subcutaneous administration of a single 40 mg dose, absorption and distribution of adalimumab was 
slow, with peak serum concentrations being reached about 5 days after administration. The average 
absolute bioavailability of adalimumab estimated from three studies following a single 40 mg 
subcutaneous dose was 64%. After single intravenous doses ranging from 0.25 to 10 mg/kg, 
concentrations were dose proportional. After doses of 0.5 mg/kg (~40 mg), clearances ranged from 11 to 
15 ml/hour, the distribution volume (Vss) ranged from 5 to 6 litres and the mean terminal phase half-life 
was approximately two weeks. Adalimumab concentrations in the synovial fluid from several rheumatoid 
arthritis patients ranged from 31-96% of those in serum. 
 
Following subcutaneous administration of 40 mg of adalimumab every other week in adult rheumatoid 
arthritis (RA) patients the mean steady-state trough concentrations were approximately 5 g/ml (without 
concomitant methotrexate) and 8 to 9 g/ml (with concomitant methotrexate), respectively.  The serum 
adalimumab trough levels at steady-state increased roughly proportionally with dose following 20, 40 and 
80 mg subcutaneous dosing every other week and every week. 
 
In adult patients with psoriasis, the mean steady-state trough concentration was 5 g/ml during 
adalimumab 40 mg every other week monotherapy treatment. 
 
In adult patients with hidradenitis suppurativa, a dose of 160 mg Humira on Week 0 followed by 80 mg on 
Week 2 achieved serum adalimumab trough concentrations of approximately 7 to 8 μg/ml at Week 2 and 
Week 4.  The mean steady-state trough concentration at Week 12 through Week 36 were approximately 8 
to 10 μg/ml during adalimumab 40 mg every week treatment.   
 
Adalimumab exposure in adolescent HS patients was predicted using population pharmacokinetic 
modelling and simulation based on cross-indication pharmacokinetics in other paediatric patients 
(paediatric psoriasis, juvenile idiopathic arthritis, paediatric Crohn’s disease, and enthesitis-related 
arthritis). The recommended adolescent HS dosing schedule is 40 mg every other week. Since exposure to 
adalimumab can be affected by body size, adolescents with higher body weight and inadequate response 
may benefit from receiving the recommended adult dose of 40 mg every week. 
 
In patients with Crohn’s disease, the loading dose of 80 mg Humira on Week 0 followed by 40 mg Humira 
on Week 2 achieves serum adalimumab trough concentrations of approximately 5.5 g/ml during the 
induction period. A loading dose of 160 mg Humira on Week 0 followed by 80 mg Humira on Week 2 
achieves serum adalimumab trough concentrations of approximately 12 g/ml during the induction period. 
Mean steady-state trough levels of approximately 7 g/ml were observed in Crohn’s disease patients who 
received a maintenance dose of 40 mg Humira every other week. 
 
In paediatric patients with moderate to severe CD, the open-label adalimumab induction dose was 
160/80 mg or 80/40 mg at Weeks 0 and 2, respectively, dependent on a body weight cut-off of 40 kg.  At 
Week 4, patients were randomised 1:1 to either the Standard Dose (40/20 mg eow) or Low Dose 
(20/10 mg eow) maintenance treatment groups based on their body weight. The mean (±SD) serum 
adalimumab trough concentrations achieved at Week 4 were 15.7 ± 6.6 g/ml for patients ≥ 40 kg 
(160/80 mg) and 10.6 ± 6.1 g/ml for patients < 40 kg (80/40 mg).  
 
For patients who stayed on their randomised therapy, the mean (±SD) adalimumab trough concentrations 
at Week 52 were 9.5 ± 5.6 g/ml for the Standard Dose group and 3.5 ± 2.2 g/ml for the Low Dose 
group.  The mean trough concentrations were maintained in patients who continued to receive adalimumab 
treatment eow for 52 weeks. For patients who dose escalated from eow to weekly regimen, the mean 



261 

(±SD) serum concentrations of adalimumab at Week 52 were 15.3 ± 11.4 μg/ml (40/20 mg, weekly) and 
6.7 ± 3.5 μg/ml (20/10 mg, weekly). 
 
In patients with ulcerative colitis, a loading dose of 160 mg Humira on Week 0 followed by 80 mg Humira 
on Week 2 achieves serum adalimumab trough concentrations of approximately 12 g/ml during the 
induction period.  Mean steady-state trough levels of approximately 8 g/ml were observed in ulcerative 
colitis patients who received a maintenance dose of 40 mg Humira every other week.  
 
Following the subcutaneous administration of body weight-based dosing of 0.6 mg/kg (maximum of 
40 mg) every other week to paediatric patients with ulcerative colitis, the mean trough steady-state serum 
adalimumab concentration was 5.01±3.28 µg/ml at Week 52. For patients who received 0.6 mg/kg 
(maximum of 40 mg) every week, the mean (±SD) trough steady-state serum adalimumab concentration 
was 15.7±5.60 μg/ml at Week 52. 
 
In adult patients with uveitis, a loading dose of 80 mg adalimumab on Week 0 followed by 40 mg 
adalimumab every other week starting at Week 1, resulted in mean steady-state concentrations of 
approximately 8 to 10 g/ml. 
 
Adalimumab exposure in paediatric uveitis patients was predicted using population pharmacokinetic 
modelling and simulation based on cross-indication pharmacokinetics in other paediatric patients 
(paediatric psoriasis, juvenile idiopathic arthritis, paediatric Crohn’s disease, and enthesitis-related 
arthritis). No clinical exposure data are available on the use of a loading dose in children < 6 years. The 
predicted exposures indicate that in the absence of methotrexate, a loading dose may lead to an initial 
increase in systemic exposure. 
 
Population pharmacokinetic and pharmacokinetic/pharmacodynamic modelling and simulation predicted 
comparable adalimumab exposure and efficacy in patients treated with 80 mg every other week when 
compared with 40 mg every week (including adult patients with RA, HS, UC, CD or Ps, patients with 
adolescent HS, and paediatric patients ≥ 40 kg with CD and UC). 
 
Exposure-response relationship in paediatric population 
On the basis of clinical trial data in patients with JIA (pJIA and ERA), an exposure-response relationship 
was established between plasma concentrations and PedACR 50 response. The apparent adalimumab 
plasma concentration that produces half the maximum probability of PedACR 50 response (EC50) was 
3 μg/ml (95% CI: 1-6 μg/ml).  
 
Exposure-response relationships between adalimumab concentration and efficacy in paediatric patients 
with severe chronic plaque psoriasis were established for PASI 75 and PGA clear or minimal, 
respectively. PASI 75 and PGA clear or minimal increased with increasing adalimumab concentrations, 
both with a similar apparent EC50 of approximately 4.5 μg/ml (95% CI 0.4-47.6 and 1.9-10.5, 
respectively).   
 
Elimination 
 
Population pharmacokinetic analyses with data from over 1,300 RA patients revealed a trend toward 
higher apparent clearance of adalimumab with increasing body weight. After adjustment for weight 
differences, gender and age appeared to have a minimal effect on adalimumab clearance.  The serum 
levels of free adalimumab (not bound to anti-adalimumab antibodies, AAA) were observed to be lower in 
patients with measurable AAA. 
 
Hepatic or renal impairment 
 
Humira has not been studied in patients with hepatic or renal impairment. 



262 

 
5.3 Preclinical safety data  
 
Non-clinical data reveal no special hazard for humans based on studies of single dose toxicity, repeated 
dose toxicity, and genotoxicity.   
 
An embryo-foetal developmental toxicity/perinatal developmental study has been performed in 
cynomolgus monkeys at 0, 30 and 100 mg/kg (9-17 monkeys/group) and has revealed no evidence of harm 
to the foetuses due to adalimumab. Neither carcinogenicity studies, nor a standard assessment of fertility 
and postnatal toxicity, were performed with adalimumab due to the lack of appropriate models for an 
antibody with limited cross-reactivity to rodent TNF and to the development of neutralising antibodies in 
rodents.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients  
 
Mannitol 
Polysorbate 80 
Water for injections 
 
6.2 Incompatibilities  
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life  
 
2 years 
 
6.4 Special precautions for storage  
 
Store in a refrigerator (2C – 8C). Do not freeze. Keep the pre-filled syringe or pre-filled pen in its outer 
carton in order to protect from light.   
 
A single Humira pre-filled syringe or pre-filled pen may be stored at temperatures up to a maximum of 
25°C for a period of up to 14 days. The syringe or pen must be protected from light, and discarded if not 
used within the 14-day period. 
 
6.5 Nature and contents of container 
 
Humira 80 mg solution for injection in pre-filled syringe 
Humira 80 mg solution for injection in single-use pre-filled syringe (type I glass) with a plunger stopper 
(bromobutyl rubber) and a needle with a needle shield (thermoplastic elastomer).  
 
Packs of: 
 1 pre-filled syringe (0.8 ml sterile solution) with 1 alcohol pad in a blister. 
 
Humira 80 mg solution for injection in pre-filled syringe with automatic needle guard 
Humira 80 mg solution for injection in single-use pre-filled syringe with automatic needle guard. The 
syringe is made from type I glass with a plunger stopper (bromobutyl rubber) and a needle with a needle 



263 

shield (thermoplastic elastomer).  
 
Packs of: 
 1 pre-filled syringe with automatic needle guard (0.8 ml sterile solution) with 1 alcohol pad in a 

blister.  
 
Humira 80 mg solution for injection in pre-filled pen 
Humira 80 mg solution for injection in single-use pre-filled pen for patient use containing a pre-filled 
syringe. The syringe inside the pen is made from type 1 glass with a plunger stopper (bromobutyl rubber) 
and a needle with a needle shield (thermoplastic elastomer). 
 
Packs of: 

 1 pre-filled pen (0.8 ml sterile solution), with 2 alcohol pads in a blister. 
 3 pre-filled pens (0.8 ml sterile solution), with 4 alcohol pads in a blister. 

 
 
Not all presentations or pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER  
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
8. MARKETING AUTHORISATION NUMBERS  
 
Humira 80 mg solution for injection in pre-filled syringe 
EU/1/03/256/020 
 
Humira 80 mg solution for injection in pre-filled syringe with automatic needle guard 
EU/1/03/256/026 
 
Humira 80 mg solution for injection in pre-filled pen 
EU/1/03/256/021 
EU/1/03/256/027 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 08 September 2003 
Date of latest renewal: 08 September 2008  
 
 



264 

10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 
  



265 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE 

SUBSTANCE AND MANUFACTURERS RESPONSIBLE FOR 
BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C.  OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 

SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 



266 

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturers of the biological active substance 
 
AbbVie Bioresearch Center 
100 Research Drive 
Worcester 
MA 01605 
USA 
 
and 
 
AbbVie Biotechnology Ltd. 
Road No. 2, Km. 59.2 
Barceloneta 
Puerto Rico 00617 
 
and 
 
Lonza Biologics Porriño,S.L 
A Relva s/n 
36400 O Porriño 
Pontevedra, Spain 
 
and 
 
Lonza Biologics Tuas PTE Ltd 
35 Tuas South Ave 6 
Singapore 637377 
 
and 
 
AbbVie Operations Singapore PTE Ltd 
23 Tuas South Avenue 6 
Singapore 637022 
 
Name and address of the manufacturers responsible for batch release 
 
AbbVie Biotechnology GmbH 
Max-Planck-Ring 2 
D-65205 Wiesbaden 
Germany 
 
and 
 
AbbVie Biotechnology GmbH 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 
The printed package leaflet of the medicinal product must state the name and address of the manufacturer 
responsible for the release of the concerned batch. 



267 

 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 

 Periodic safety update reports (PSURs) 
The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 

USE OF THE MEDICINAL PRODUCT 
 
 Risk management plan (RMP) 
 
The marketing authorization holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing 
authorisation and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 

 At the request of the European Medicines Agency;  
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of an 
important (pharmacovigilance or risk minimisation) milestone being reached. 

 
 Additional risk minimisation measures 

   
The Patient Reminder Cards (adult and paediatric) contain the following key elements 
 
- infections, including tuberculosis 
- cancer 
- nervous system problems 
- vaccinations 
 
  



268 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 

  



269 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
A. LABELLING 

 



270 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 20 mg solution for injection in pre-filled syringe 
adalimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One 0.2 ml pre-filled syringe contains 20 mg adalimumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: mannitol, polysorbate 80, and water for injections. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
2 pre-filled syringes 
2 alcohol pads  
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Subcutaneous use 
 
Read the package leaflet before use. 
 
For single use only. 
 
For paediatric use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 



271 

 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze.  
Refer to package leaflet for alternative storage details. 
 
Keep the syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/03/256/022 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Humira 20 mg 
 
 
17.  UNIQUE INDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



272 

18.  UNIQUE INDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 
  



273 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY BACKING TEXT 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 20 mg solution for injection in pre-filled syringe  
adalimumab 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie (as logo) 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
For storage information, see package leaflet. 
 
For single use only. 
 
For paediatric use 
 
 
 



274 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SYRINGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Humira 20 mg injection 
adalimumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
20 mg/0.2 ml 
 
 
6. OTHER 



275 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 40 mg/0.8 ml solution for injection 
adalimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One 0.8 ml vial contains 40 mg adalimumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen phosphate dihydrate, 
disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and water for 
injections. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
Contains 2 cartons each for a single injection only 
Each carton contains: 
1 vial  
1 sterile injection syringe  
1 sterile needle 
1 sterile vial adapter 
2 alcohol pads  
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Subcutaneous use 
 
Read the package leaflet before use. 
 
For paediatric use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING, IF NECESSARY 



276 

 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze. 
Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/03/256/001 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Humira 40 mg 
 
 
17.  UNIQUE INDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 



277 

 
18.  UNIQUE INDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 



278 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
INNER CARTON		
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 40 mg/0.8 ml solution for injection 
adalimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One 0.8 ml vial contains 40 mg adalimumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen phosphate dihydrate, 
disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and water for 
injections. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 vial  
1 sterile injection syringe  
1 sterile needle 
1 sterile vial adapter 
2 alcohol pads  
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Subcutaneous use 
 
Read the package leaflet before use. 
 
For single use only.  
 
For paediatric use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING, IF NECESSARY 



279 

 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze. 
Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/03/256/001 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Humira 40 mg 
 
 
17.  UNIQUE INDENTIFIER – 2D BARCODE 
 
 



280 

18.  UNIQUE INDENTIFIER – HUMAN READABLE DATA 
 



281 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Humira 40 mg/0.8 ml injection 
adalimumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
40 mg/0.8 ml 
 
 

6. OTHER 
 
For single use only 
 



282 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 40 mg solution for injection in pre-filled syringe  
adalimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One 0.8 ml pre-filled syringe contains 40 mg adalimumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients:  mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen phosphate dihydrate, 
disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and water for 
injections. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 pre-filled syringe 
1 alcohol pad 
 
2 pre-filled syringes 
2 alcohol pads  
 
4 pre-filled syringes 
4 alcohol pads  
 
6 pre-filled syringes 
6 alcohol pads  
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Subcutaneous use 
 
Read the package leaflet before use. 
 
For single use only. 
 
 



283 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 
THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze. 
Refer to package leaflet for alternative storage details. 
 
Keep the syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/03/256/002 
EU/1/03/256/003 
EU/1/03/256/004 
EU/1/03/256/005 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 



284 

15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Humira 40 mg 
 
 
17.  UNIQUE INDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18.  UNIQUE INDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 

  



285 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY BACKING TEXT 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 40 mg solution for injection in pre-filled syringe 
adalimumab 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie (as logo) 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. OTHER 
 
For storage information, see package leaflet. 
 
For single use only. 
 



286 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SYRINGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Humira 40 mg injection 
adalimumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
40 mg/0.8 ml 
 
 
6. OTHER 
 
 



287 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING OR, WHERE THERE IS NO 
OUTER PACKAGING, ON THE IMMEDIATE PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 40 mg solution for injection in pre-filled syringe 
adalimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One 0.8 ml pre-filled syringe with needle guard contains 40 mg adalimumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen phosphate dihydrate, 
disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and water for 
injections. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 pre-filled syringe 
1 alcohol pad 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Subcutaneous use 
 
Read the package leaflet before use. 
 
For single use only. 
 
With needle guard. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING, IF NECESSARY 
 
 



288 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze.  
Refer to package leaflet for alternative storage details. 
 
Keep the syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/03/256/006 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Humira 40 mg 
 
 
17.  UNIQUE INDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 



289 

 
18.  UNIQUE INDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



290 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY BACKING TEXT 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 40 mg solution for injection in pre-filled syringe 
adalimumab 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie (as logo) 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. OTHER 
 
For storage information, see package leaflet. 
 
For single use only. 
 
With needle guard. 



291 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SYRINGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Humira 40 mg injection  
adalimumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
40 mg/0.8 ml 
 
 
6. OTHER 
 
 



292 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 40 mg solution for injection in pre-filled pen 
adalimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One 0.8 ml pre-filled pen contains 40 mg adalimumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen phosphate dihydrate, 
disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and water for 
injections. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 pre-filled pen 
2 alcohol pads  
 
2 pre-filled pens 
2 alcohol pads  
 
4 pre-filled pens 
4 alcohol pads  
 
6 pre-filled pens 
6 alcohol pads  
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Subcutaneous use 
 
Read the package leaflet before use. 
 
For single use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 



293 

 
 
7. OTHER SPECIAL WARNING, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze.  
Refer to package leaflet for alternative storage details. 
 
Keep the pre-filled pen in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/03/256/007 
EU/1/03/256/008 
EU/1/03/256/009 
EU/1/03/256/010 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 



294 

16. INFORMATION IN BRAILLE 
 
Humira 40 mg 
 
 
17.  UNIQUE INDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18.  UNIQUE INDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 
 

  



295 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY BACKING TEXT 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 40 mg solution for injection in pre-filled pen 
adalimumab 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie (as logo) 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. OTHER 
 
For storage information, see package leaflet. 
 
For single use only. 
 



296 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PEN LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Humira 40 mg injection 
adalimumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
40 mg/0.8 ml 
 
 
6. OTHER 
 
 



297 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 40 mg solution for injection in pre-filled syringe  
adalimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One 0.4 ml pre-filled syringe contains 40 mg adalimumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: mannitol, polysorbate 80, and water for injections. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 pre-filled syringe 
1 alcohol pad 
 
2 pre-filled syringes 
2 alcohol pads  
 
4 pre-filled syringes 
4 alcohol pads 
 
6 pre-filled syringes 
6 alcohol pads  
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Subcutaneous use 
 
Read the package leaflet before use. 
 
For single use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 



298 

 
7. OTHER SPECIAL WARNING, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze. 
Refer to package leaflet for alternative storage details. 
 
Keep the syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/03/256/012 
EU/1/03/256/013 
EU/1/03/256/014 
EU/1/03/256/015 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 



299 

16. INFORMATION IN BRAILLE 
 
Humira 40 mg 
 
 
17.  UNIQUE INDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18.  UNIQUE INDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



300 

  
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY BACKING TEXT 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 40 mg solution for injection in pre-filled syringe 
adalimumab 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie (as logo) 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
For storage information, see package leaflet. 
 
For single use only. 
 
40 mg/0.4 ml 
 
 
 
 
 
 



301 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SYRINGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Humira 40 mg injection 
adalimumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
40 mg/0.4 ml 
 
 
6. OTHER 
 
 
  



302 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING OR, WHERE THERE IS NO 
OUTER PACKAGING, ON THE IMMEDIATE PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 40 mg solution for injection in pre-filled syringe 
adalimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One 0.4 ml pre-filled syringe with automatic needle guard contains 40 mg adalimumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: mannitol, polysorbate 80, and water for injections. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 pre-filled syringe 
1 alcohol pad 
 
2 pre-filled syringes 
2 alcohol pads 
 
6 pre-filled syringes 
6 alcohol pads 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Subcutaneous use 
 
Read the package leaflet before use. 
 
For single use only. 
 
With automatic needle guard 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 



303 

7. OTHER SPECIAL WARNING, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze.  
Refer to package leaflet for alternative storage details. 
 
Keep the syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/03/256/023 
EU/1/03/256/024 
EU/1/03/256/025 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Humira 40 mg 
 



304 

 
17.  UNIQUE INDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18.  UNIQUE INDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



305 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY BACKING TEXT 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 40 mg solution for injection in pre-filled syringe 
adalimumab 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie (as logo) 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. OTHER 
 
For storage information, see package leaflet. 
 
For single use only. 
 
With automatic needle guard. 
 
 
 
 



306 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SYRINGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Humira 40 mg injection  
adalimumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
40 mg/0.4 ml 
 
 
6. OTHER 
 
 



307 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 40 mg solution for injection in pre-filled pen 
adalimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One 0.4 ml pre-filled pen contains 40 mg adalimumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: mannitol, polysorbate 80 and water for injections. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 pre-filled pen 
2 alcohol pads 
 
2 pre-filled pens 
2 alcohol pads  
 
4 pre-filled pens 
4 alcohol pads  
 
6 pre-filled pens 
6 alcohol pads  
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Subcutaneous use 
 
Read the package leaflet before use. 
 
For single use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 



308 

 
7. OTHER SPECIAL WARNING, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze.  
Refer to package leaflet for alternative storage details. 
 
Keep the pre-filled pen in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/03/256/016 
EU/1/03/256/017 
EU/1/03/256/018 
EU/1/03/256/019 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 



309 

16. INFORMATION IN BRAILLE 
 
Humira 40 mg 
 
 
17.  UNIQUE INDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18.  UNIQUE INDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 
 

  



310 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY BACKING TEXT 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 40 mg solution for injection in pre-filled pen 
adalimumab 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie (as logo) 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. OTHER 
 
For storage information, see package leaflet. 
 
For single use only. 
 
40 mg/0.4 ml 
 
 
 
 
 



311 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PEN LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Humira 40 mg injection 
adalimumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
40 mg/0.4 ml 
 
 
6. OTHER 
 
 



312 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 80 mg solution for injection in pre-filled syringe  
adalimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One 0.8 ml pre-filled syringe contains 80 mg adalimumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: mannitol, polysorbate 80, and water for injections. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 pre-filled syringe 
1 alcohol pad 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Subcutaneous use 
 
Read the package leaflet before use. 
 
For single use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



313 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze. 
Refer to package leaflet for alternative storage details. 
 
Keep the syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/03/256/020 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Humira 80 mg 
 
 
17.  UNIQUE INDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18.  UNIQUE INDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 



314 

NN 
 



315 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY BACKING TEXT 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 80 mg solution for injection in pre-filled syringe 
adalimumab 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie (as logo) 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
For storage information, see package leaflet. 
 
For single use only. 
 
 
 
 
 



316 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SYRINGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Humira 80 mg injection 
adalimumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
80 mg/0.8 ml 
 
 
6. OTHER 
 
  



317 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 80 mg solution for injection in pre-filled syringe  
adalimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One 0.8 ml pre-filled syringe with automatic needle guard contains 80 mg adalimumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: mannitol, polysorbate 80, and water for injections. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 pre-filled syringe 
1 alcohol pad 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Subcutaneous use 
 
Read the package leaflet before use. 
 
For single use only. 
 
With automatic needle guard  
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING, IF NECESSARY 
 
 



318 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze. 
Refer to package leaflet for alternative storage details. 
 
Keep the syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany   
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/03/256/026 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Humira 80 mg 
 
 
17.  UNIQUE INDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 



319 

 
18.  UNIQUE INDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



320 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY BACKING TEXT 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 80 mg solution for injection in pre-filled syringe 
adalimumab 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie (as logo) 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
For storage information, see package leaflet. 
 
For single use only. 
 
With automatic needle guard. 
 
 
 
 



321 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SYRINGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Humira 80 mg injection 
adalimumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
80 mg/0.8 ml 
 
 
6. OTHER 
 



322 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 80 mg solution for injection in pre-filled pen 
adalimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One 0.8 ml pre-filled pen contains 80 mg adalimumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: mannitol, polysorbate 80 and water for injections. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 pre-filled pen 
2 alcohol pads 
 
3 pre-filled pens 
4 alcohol pads 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Subcutaneous use 
 
Read the package leaflet before use. 
 
For single use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING, IF NECESSARY 
 
 
8. EXPIRY DATE 
 



323 

EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze.  
Refer to package leaflet for alternative storage details. 
 
Keep the pre-filled pen in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/03/256/021 
EU/1/03/256/027 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Humira 80 mg 
 
 
17.  UNIQUE INDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



324 

18.  UNIQUE INDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



325 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY BACKING TEXT 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Humira 80 mg solution for injection in pre-filled pen 
adalimumab 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie (as logo) 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. OTHER 
 
For storage information, see package leaflet. 
 
For single use only. 
 
 
 
 
 



326 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PEN LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Humira 80 mg injection 
adalimumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
80 mg/0.8 ml 
 
 
6. OTHER 
 



327 

REMINDER STICKERS TEXT (included in pack) 
 
 
Humira  
 
Mark your calendar with the stickers provided to remind you of the date for your next dose. 
 
  



328 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 

 



329 

  
Package leaflet: Information for the patient 

 
Humira 20 mg solution for injection in pre-filled syringe 

adalimumab 
 

Read all of this leaflet carefully before your child starts using this medicine because it contains 
important information. 
 Keep this leaflet. You may need to read it again. 
 Your doctor will also give you a Patient Reminder Card, which contains important safety 

information that you need to be aware of before your child begins using Humira and during 
treatment with Humira. Keep this Patient Reminder Card with you or your child. 

 If you have any questions, ask your doctor or pharmacist. 
 This medicine has been prescribed for your child only. Do not pass it on to others. It may harm 

them, even if their signs of illness are the same as your child. 
 If your child gets any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet  
1. What Humira is and what it is used for 
2. What you need to know before your child uses Humira 
3. How to use Humira 
4. Possible side effects 
5 How to store Humira 
6. Contents of the pack and other information 
7. Injecting Humira 
 
 
1. What Humira is and what it is used for 
  
Humira contains the active substance adalimumab. 
 
Humira is intended for the treatment of the inflammatory diseases described below: 

 Polyarticular juvenile idiopathic arthritis 
 Enthesitis-related arthritis 
 Paediatric plaque psoriasis 
 Paediatric Crohn’s disease 
 Paediatric uveitis 

 
The active ingredient in Humira, adalimumab, is a human monoclonal antibody. Monoclonal antibodies 
are proteins that attach to a specific target. 
 
The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the 
immune (defence) system and is present at increased levels in the inflammatory diseases listed above. By 
attaching to TNFα, Humira decreases the process of inflammation in these diseases. 
 
Polyarticular juvenile idiopathic arthritis 
 
Polyarticular juvenile idiopathic arthritis is an inflammatory disease of the joints that usually first appears 
in childhood. 
 



330 

Humira is used to treat polyarticular juvenile idiopathic arthritis in patients from 2 years of age. Your child 
may first be given other disease-modifying medicines, such as methotrexate. If these medicines do not 
work well enough, your child will be given Humira to treat his/her polyarticular juvenile idiopathic 
arthritis. 
 
Your doctor will decide if Humira should be used with methotrexate or alone. 
 
Enthesitis-related arthritis 
 
Enthesitis-related arthritis is an inflammatory disease of the joints and the places where tendons join the 
bone. 
 
Humira is used to treat enthesitis-related arthritis in patients from 6 years of age. Your child may first be 
given other disease-modifying medicines, such as methotrexate. If these medicines do not work well 
enough, your child will be given Humira to treat his/her enthesitis-related arthritis. 
 
Paediatric plaque psoriasis  
 
Plaque psoriasis is a skin condition that causes red, flaky, crusty patches of skin covered with silvery 
scales. Plaque psoriasis can also affect the nails, causing them to crumble, become thickened and lift away 
from the nail bed which can be painful. Psoriasis is believed to be caused by a problem with the body’s 
immune system that leads to an increased production of skin cells. 
 
Humira is used to treat severe chronic plaque psoriasis in children and adolescents aged 4 to 17 years for 
whom topical therapy and phototherapies have either not worked very well or are not suitable. 
 

Paediatric Crohn’s disease 
 
Crohn’s disease is an inflammatory disease of the digestive tract. 
 
Humira is used to treat moderate to severe Crohn’s disease in children and adolescents aged 6 to 17 years. 
 
Your child may first be given other medicines. If these medicines do not work well enough, your child 
will be given Humira to reduce the signs and symptoms of his/her disease. 
 
Paediatric uveitis 
 
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. 
 
Humira is used to treat children with chronic non-infectious uveitis from 2 years of age with inflammation 
affecting the front of the eye  
 
This inflammation may lead to a decrease of vision and/or the presence of floaters in the eye (black dots or 
wispy lines that move across the field of vision). Humira works by reducing this inflammation. 
 
Your child may first be given other medicines. If these medicines do not work well enough, your child 
will be given Humira to reduce the signs and symptoms of his/her disease. 
 
 



331 

2. What you need to know before your child uses Humira 
 
Do not use Humira: 
 

 If your child is allergic to adalimumab or any of the other ingredients of this medicine (listed in 
section 6).  

 
 If your child has active tuberculosis or other severe infections (see “Warnings and precautions”). 

It is important that you tell your doctor if your child has symptoms of infections, for example, 
fever, wounds, feeling tired, dental problems. 

 
 If your child has moderate or severe heart failure. It is important to tell your doctor if your child 

has had or has a serious heart condition (see “Warnings and precautions”). 
 
Warnings and precautions 
 
Talk to your doctor or pharmacist before using Humira. 
 
Allergic reactions 
 

 If your child gets allergic reactions with symptoms such as chest tightness, wheezing, dizziness, 
swelling or rash do not inject more Humira and contact your doctor immediately since, in rare 
cases, these reactions can be life threatening. 

 
Infections 
 

 If your child has an infection, including long-term infection or an infection in one part of the body 
(for example, leg ulcer) consult your doctor before starting Humira. If you are unsure, contact 
your doctor.  

 
 Your child might get infections more easily while he/she is receiving Humira treatment. This risk 

may increase if your child has problems with his/her lungs. These infections may be serious and 
include:  

 tuberculosis 
 infections caused by viruses, fungi, parasites or bacteria 
 severe infection in the blood (sepsis) 

 
In rare cases, these infections can be life-threatening. It is important to tell your doctor if your 
child gets symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may tell 
you to stop using Humira for some time. 
 

 Tell your doctor if your child lives or travels in regions where fungal infections (for example, 
histoplasmosis, coccidioidomycosis or blastomycosis) are very common. 

 
 Tell your doctor if your child has had infections which keep coming back or other conditions that 

increase the risk of infections. 
 

 Your child and his/her doctor should pay special attention to signs of infection while your child is 
being treated with Humira. It is important to tell your doctor if your child gets symptoms of 
infections, such as fever, wounds, feeling tired or dental problems. 

 



332 

Tuberculosis 
 

 As cases of tuberculosis have been reported in patients treated with Humira, your doctor will 
check your child for signs and symptoms of tuberculosis before starting Humira. This will include 
a thorough medical evaluation including your child’s medical history and appropriate screening 
tests (for example, chest X-ray and a tuberculin test). The conduct and results of these tests should 
be recorded on your child’s Patient Reminder Card.  

 
 It is very important that you tell your doctor if your child has ever had tuberculosis, or if 

your child has been in close contact with someone who has had tuberculosis. If your child 
has active tuberculosis, do not use Humira. 

 Tuberculosis can develop during therapy even if your child has received treatment for the 
prevention of tuberculosis.  

 If symptoms of tuberculosis (for example, cough that does not go away, weight loss, lack 
of energy, mild fever), or any other infection appear during or after therapy tell your 
doctor immediately. 
 

Hepatitis B 
 

 Tell your doctor if your child is a carrier of the hepatitis B virus (HBV), if he/she has active HBV 
or if you think he/she might be at risk of getting HBV.  

 Your doctor should test your child for HBV. In people who carry HBV, Humira can cause 
the virus to become active again. 

 In some rare cases, especially if your child is taking other medicines that suppress the 
immune system, reactivation of HBV can be life-threatening.   

 
Surgery or dental procedure 
 

 If your child is about to have surgery or dental procedures please inform your doctor that your 
child is taking Humira. Your doctor may recommend temporary discontinuation of Humira.  

 
Demyelinating disease 
 

 If your child has or develops a demyelinating disease (a disease that affects the insulating layer 
around the nerves, such as multiple sclerosis), your doctor will decide if he/she should receive or 
continue to receive Humira. Tell your doctor immediately if your child experiences symptoms like 
changes in vision, weakness in arms or legs or numbness or tingling in any part of the body. 

 
Vaccinations 
 

 Certain vaccines may cause infections and should not be given while receiving Humira.  
 

 Check with your doctor before your child receives any vaccines.  
 It is recommended that children, if possible, be given all the scheduled vaccinations for 

their age before they start treatment with Humira. 
 If your child received Humira while she was pregnant, her baby may be at higher risk for 

getting such an infection for up to approximately five months after the last Humira dose 
she received during pregnancy. It is important that you tell her baby's doctors and other 
health care professionals about your child’s Humira use during her pregnancy so they can 
decide when her baby should receive any vaccine. 

 



333 

Heart failure 
 

 If your child has mild heart failure and is being treated with Humira, his/her heart failure status 
must be closely monitored by your doctor. It is important to tell your doctor if your child has had 
or has a serious heart condition. If he/she develops new or worsening symptoms of heart failure 
(e.g. shortness of breath, or swelling of your feet), you must contact your doctor immediately. 
Your doctor will decide if your child should receive Humira. 

 
Fever, bruising, bleeding or looking pale 
 

 In some patients the body may fail to produce enough of the blood cells that fight off infections or 
help your child to stop bleeding. Your doctor may decide to stop treatment. If your child develops 
a fever that does not go away, develops light bruises or bleeds very easily or looks very pale, call 
your doctor right away. 

 
Cancer 
 

 There have been very rare cases of certain kinds of cancer in children and adult patients taking 
Humira or other TNF blockers.   

 
 People with more serious rheumatoid arthritis that have had the disease for a long time 

may have a higher than average risk of getting lymphoma (a cancer that affects the lymph 
system) and leukaemia (a cancer that affects the blood and bone marrow).  

 If your child takes Humira the risk of getting lymphoma, leukaemia, or other cancers may 
increase. On rare occasions, an uncommon and severe type of lymphoma, has been seen in 
patients taking Humira. Some of those patients were also treated with azathioprine or 6-
mercaptopurine.  

 Tell your doctor if your child is taking azathioprine or 6-mercaptopurine with Humira.  
 Cases of non-melanoma skin cancer have been observed in patients taking Humira.  
 If new skin lesions appear during or after therapy or if existing lesions change appearance, 

tell your doctor. 
 

 There have been cases of cancers, other than lymphoma in patients with a specific type of lung 
disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another TNF blocker. 
If your child has COPD, or is a heavy smoker, you should discuss with your doctor whether 
treatment with a TNF blocker is appropriate for your child. 

 
Autoimmune disease 
 

 On rare occasions, treatment with Humira could result in lupus-like syndrome. Contact your 
doctor if symptoms such as persistent unexplained rash, fever, joint pain or tiredness occur. 
 

Other medicines and Humira 
 
Tell your doctor or pharmacist if your child is taking, has recently taken or might take any other 
medicines. 
 
Your child should not take Humira with medicines containing the following active substances due to 
increased risk of serious infection: 

 anakinra 
 abatacept. 

 



334 

Humira can be taken together with: 
 methotrexate 
 certain disease-modifying anti-rheumatic agents (for example, sulfasalazine, hydroxychloroquine, 

leflunomide and injectable gold preparations) 
 steroids or pain medications including non-steroidal anti-inflammatory drugs (NSAIDs). 

 
If you have questions, please ask your doctor. 
 
Pregnancy and breast-feeding 
 

 Your child should consider the use of adequate contraception to prevent pregnancy and continue 
its use for at least 5 months after the last Humira treatment. 

 If your child is pregnant, thinks she may be pregnant or is planning to have a baby, ask her doctor 
for advice about taking this medicine. 

 Humira should only be used during a pregnancy if needed. 
 According to a pregnancy study, there was no higher risk of birth defects when the mother had 

received Humira during pregnancy compared with mothers with the same disease who did not 
receive Humira. 

 Humira can be used during breast-feeding. 
 If your child received Humira during her pregnancy, her baby may have a higher risk for getting 

an infection. 
 It is important that you tell her baby’s doctor and other health care professionals about her Humira 

use during her pregnancy before the baby receives any vaccine. For more information on vaccines 
see the “Warnings and precautions” section. 
 

Driving and using machines 
 
Humira may have a small effect on your child’s ability to drive, cycle or use machines. Room spinning 
sensation and vision disturbances may occur after taking Humira. 
 
 
3. How to use Humira 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are not sure.  
 
The recommended doses for Humira in each of the approved uses are shown in the following table. Your 
doctor may prescribe another strength of Humira if your child needs a different dose. 
 

Polyarticular juvenile idiopathic arthritis
Age or body weight How much and how often to 

take?
Notes 

Children, adolescents and adults 
from 2 years of age weighing 30 
kg or more 

40 mg every other week Not applicable 

Children and adolescents from 2 
years of age weighing 10 kg to 
less than 30 kg 

20 mg every other week Not applicable 

 
Enthesitis-related arthritis 
Age or body weight How much and how often to 

take?
Notes 



335 

Children, adolescents and adults 
from 6 years of age weighing 30 
kg or more 

40 mg every other week Not applicable 

Children and adolescents from 6 
years of age weighing 15 kg to 
less than 30 kg 

20 mg every other week Not applicable 

 
Paediatric plaque psoriasis 
Age or body weight How much and how often to 

take?
Notes 

Children and adolescents from 4 
to 17 years of age weighing 30 
kg or more 

First dose of 40 mg, followed by 
40 mg one week later. 
 
Thereafter, the usual dose is 40 
mg every other week.

Not applicable 

Children and adolescents from 4 
to 17 years of age weighing 15 
kg to less than 30 kg 

First dose of 20 mg, followed by 
20 mg one week later. 
 
Thereafter, the usual dose is 20 
mg every other week.

Not applicable 

 
Paediatric Crohn’s disease 
Age or body weight How much and how often to 

take?
Notes 

Children and adolescents from 6 
to 17 years of age weighing 40 
kg or more 
 
 

First dose of 80 mg, followed by 
40 mg two weeks later. 
 
If a faster response is required, 
your child’s doctor may 
prescribe a first dose of 160 mg, 
followed by 80 mg two weeks 
later. 
 
Thereafter, the usual dose is 40 
mg every other week.

Your child’s doctor may 
increase the dosage to 40 mg 
every week or 80 mg every 
other week. 
 

Children and adolescents from 6 
to 17 years of age weighing less 
than 40 kg 

First dose of 40 mg, followed by 
20 mg two weeks later.  
 
If a faster response is required, 
the doctor may prescribe a first 
dose of 80 mg, followed by 40 
mg two weeks later. 
 
Thereafter, the usual dose is 20 
mg every other week.

Your child’s doctor may 
increase the dose frequency to 
20 mg every week. 
 

 



336 

Paediatric uveitis 
Age or body weight How much and how often to 

take?
Notes 

Children and adolescents from 
2 years of age weighing less 
than 30 kg 
 

20 mg every other week Your doctor may prescribe an 
initial dose of 40 mg to be 
administered one week prior to 
the start of the usual dose of 
20 mg every other week. 
Humira is recommended for use 
in combination with 
methotrexate. 

Children and adolescents from 
2 years of age weighing 30 kg 
or more 
 

40 mg every other week  Your doctor may prescribe an 
initial dose of 80 mg to be 
administered one week prior to 
the start of the usual dose of 
40 mg every other week. 
Humira is recommended for use 
in combination with 
methotrexate. 

 
Method and route of administration 
 
Humira is administered by injection under the skin (by subcutaneous injection). 
 
Detailed instructions on how to inject Humira are provided in section 7 ‘Injecting Humira’. 
 
If you use more Humira than you should 
 
If you accidentally inject Humira more frequently than told to by your doctor or pharmacist, call your 
doctor or pharmacist and tell them that your child has taken more. Always take the outer carton of the 
medicine with you, even if it is empty.  
 
If you forget to use Humira 
 
If you forget to give your child an injection, you should inject the next dose of Humira as soon as you 
remember. Then give your child’s next dose as you would have on the originally scheduled day, had you 
not forgotten a dose.  
 
If you stop using Humira 
 
The decision to stop using Humira should be discussed with your doctor. Your child’s symptoms may 
return if you stop using Humira. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side 
effects are mild to moderate. However, some may be serious and require treatment. Side effects may occur 
at least up to 4 months after the last Humira injection.  
 



337 

Tell your doctor immediately if you notice any of the following 
 
 severe rash, hives or other signs of allergic reaction  
 swollen face, hands, feet 
 trouble breathing, swallowing 
 shortness of breath with physical activity or upon lying down or swelling of the feet 
 
Tell your doctor as soon as possible if you notice any of the following 
 
 signs of infection such as fever, feeling sick, wounds, dental problems, burning on urination 
 feeling weak or tired 
 coughing 
 tingling 
 numbness 
 double vision 
 arm or leg weakness 
 a bump or open sore that doesn't heal 
 signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, 

paleness 
 
The symptoms described above can be signs of the below listed side effects, which have been observed 
with Humira. 
 
Very common (may affect more than 1 in 10 people)   
 
 injection site reactions (including pain, swelling, redness or itching) 
 respiratory tract infections (including cold, runny nose, sinus infection, pneumonia) 
 headache 
 abdominal pain 
 nausea and vomiting 
 rash 
 musculoskeletal pain 
 
Common (may affect up to 1 in 10 people)  
 
 serious infections (including blood poisoning and influenza) 
 intestinal infections (including gastroenteritis) 
 skin infections (including cellulitis and shingles) 
 ear infections 
 oral infections (including tooth infections and cold sores) 
 reproductive tract infections 
 urinary tract infection 
 fungal infections 
 joint infections 
 benign tumours 
 skin cancer 
 allergic reactions (including seasonal allergy) 
 dehydration 
 mood swings (including depression) 
 anxiety 
 difficulty sleeping 



338 

 sensation disorders such as tingling, prickling or numbness 
 migraine 
 nerve root compression (including low back pain and leg pain) 
 vision disturbances 
 eye inflammation 
 inflammation of the eye lid and eye swelling 
 vertigo (feeling of dizziness or spinning) 
 sensation of heart beating rapidly 
 high blood pressure 
 flushing 
 haematoma (collection of blood outside of blood vessels) 
 cough 
 asthma 
 shortness of breath 
 gastrointestinal bleeding 
 dyspepsia (indigestion, bloating, heart burn) 
 acid reflux disease 
 sicca syndrome (including dry eyes and dry mouth) 
 itching 
 itchy rash 
 bruising 
 inflammation of the skin (such as eczema) 
 breaking of finger nails and toe nails 
 increased sweating 
 hair loss 
 new onset or worsening of psoriasis 
 muscle spasms 
 blood in urine 
 kidney problems 
 chest pain 
 oedema (swelling) 
 fever 
 reduction in blood platelets which increases risk of bleeding or bruising 
 impaired healing 
 
Uncommon (may affect up to 1 in 100 people)   
 
 opportunistic infections (which include tuberculosis and other infections that occur when resistance 

to disease is lowered) 
 neurological infections (including viral meningitis) 
 eye infections 
 bacterial infections 
 diverticulitis (inflammation and infection of the large intestine) 
 cancer 
 cancer that affects the lymph system 
 melanoma 
 immune disorders that could affect the lungs, skin and lymph nodes (most commonly presenting as 

sarcoidosis) 
 vasculitis (inflammation of blood vessels) 
 tremor (shaking) 



339 

 neuropathy (disorder of the nerves) 
 stroke 
 hearing loss, buzzing 
 sensation of heart beating irregularly such as skipped beats 
 heart problems that can cause shortness of breath or ankle swelling 
 heart attack 
 a sac in the wall of a major artery, inflammation and clot of a vein, blockage of a blood vessel 
 lung diseases causing shortness of breath (including inflammation) 
 pulmonary embolism (blockage in an artery of the lung) 
 pleural effusion (abnormal collection of fluid in the pleural space) 
 inflammation of the pancreas which causes severe pain in the abdomen and back 
 difficulty in swallowing 
 facial oedema (swelling of the face) 
 gallbladder inflammation, gallbladder stones 
 fatty liver 
 night sweats 
 scar 
 abnormal muscle breakdown 
 systemic lupus erythematosus (including inflammation of skin, heart, lung, joints and other organ 

systems) 
 sleep interruptions 
 impotence 
 inflammations 
 
Rare (may affect up to 1 in 1,000 people) 
 
 leukaemia (cancer affecting the blood and bone marrow) 
 severe allergic reaction with shock 
 multiple sclerosis 
 nerve disorders (such as eye nerve inflammation and Guillain-Barré syndrome that may cause 

muscle weakness, abnormal sensations, tingling in the arms and upper body) 
 heart stops pumping 
 pulmonary fibrosis (scarring of the lung) 
 intestinal perforation (hole in the intestine) 
 hepatitis 
 reactivation of hepatitis B 
 autoimmune hepatitis (inflammation of the liver caused by the body's own immune system) 
 cutaneous vasculitis (inflammation of blood vessels in the skin) 
 Stevens-Johnson syndrome (early symptoms include malaise, fever, headache and rash) 
 facial oedema (swelling of the face) associated with allergic reactions 
 erythema multiforme (inflammatory skin rash) 
 lupus-like syndrome 
 angioedema (localized swelling of the skin) 
 lichenoid skin reaction (itchy reddish-purple skin rash) 
 
Not known (frequency cannot be estimated from the available data) 
 
 hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal) 
 Merkel cell carcinoma (a type of skin cancer) 



340 

 Kaposi’s sarcoma, a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma 
most commonly appears as purple lesions on the skin 

 liver failure 
 worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle        

weakness) 
 
Some side effects observed with Humira may not have symptoms and may only be discovered through 
blood tests. These include: 
 
Very common (may affect more than 1 in 10 people) 
 
 low blood measurements for white blood cells 
 low blood measurements for red blood cells 
 increased lipids in the blood 
 elevated liver enzymes 
 
Common (may affect up to 1 in 10 people) 
 
 high blood measurements for white blood cells 
 low blood measurements for platelets 
 increased uric acid in the blood 
 abnormal blood measurements for sodium 
 low blood measurements for calcium 
 low blood measurements for phosphate 
 high blood sugar 
 high blood measurements for lactate dehydrogenase 
 autoantibodies present in the blood 
 low blood potassium 
 
Uncommon (may affect up to 1 in 100 people)  
 
 elevated bilirubin measurement (liver blood test) 
 
Rare (may affect up to 1 in 1,000 people) 
 
 low blood measurements for white blood cells, red blood cells and platelet count 
 
Reporting of side effects 
If your child gets any side effects, talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects, you can help provide more information on the safety of 
this medicine.  
 
 
5. How to store Humira 
 
Keep this medicine out of the sight and reach of children.  
 
Do not use this medicine after the expiry date stated on the label/blister/carton after EXP.  
 
Store in a refrigerator (2C – 8C). Do not freeze.  
 



341 

Keep the pre-filled syringe in the outer carton in order to protect from light.   
 
Alternative Storage: 
 
When needed (for example, when you are travelling), a single Humira pre-filled syringe may be stored at 
room temperature (up to 25°C) for a maximum period of 14 days – be sure to protect it from light. Once 
removed from the refrigerator for room temperature storage, the syringe must be used within 14 days or 
discarded, even if it is returned to the refrigerator.   
 
You should record the date when the syringe is first removed from refrigerator and the date after which it 
should be discarded. 
 
Do not throw away any medicines via wastewater or household waste. Ask your doctor or pharmacist how 
to throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Humira contains 
 
The active substance is adalimumab. 
The other ingredients are mannitol, polysorbate 80 and water for injections. 
 
What the Humira pre-filled syringe looks like and contents of the pack 
 
Humira 20 mg solution for injection in pre-filled syringe for paediatric use is supplied as a sterile solution 
of 20 mg adalimumab dissolved in 0.2 ml solution. 
 
The Humira pre-filled syringe is a glass syringe containing a solution of adalimumab.   
 
The Humira pre-filled syringe is available in a pack containing 2 pre-filled syringes with 2 alcohol pads.   
 
Humira may be available as a vial, a pre-filled syringe and/or a pre-filled pen. 
 
Marketing Authorisation Holder 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
Manufacturer  
 
AbbVie Biotechnology GmbH 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
AbbVie SA 

Lietuva 
AbbVie UAB 



342 

Tél/Tel: +32 10  477811 Tel: +370 5 205 3023 
България 
АбВи ЕООД 
Тел.:+359 2 90 30 430 

Luxembourg/Luxemburg 
AbbVie SA 
Belgique/Belgien 
Tél/Tel: +32 10 477811

Česká republika 
AbbVie s.r.o.  
Tel: +420 233 098 111 

Magyarország 
AbbVie Kft. 
Tel.:+36 1 455 8600

Danmark 
AbbVie A/S 
Tlf: +45 72 30-20-28 

Malta 
V.J.Salomone Pharma Limited  
Tel: +356 22983201

Deutschland 
AbbVie Deutschland GmbH & Co. KG 
Tel: 00800 222843 33 (gebührenfrei) 
Tel: +49 (0) 611 / 1720-0

Nederland 
AbbVie B.V. 
Tel:  +31 (0)88 322 2843 

Eesti 
AbbVie Biopharmaceuticals GmbH Eesti filiaal  
Tel: +372 623 1011 

Norge 
AbbVie AS 
Tlf: +47 67 81 80 00

Ελλάδα 
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. 
Τηλ: +30 214 4165 555 

Österreich 
AbbVie GmbH  
Tel: +43 1 20589-0 

España 
AbbVie Spain, S.L.U. 
Tel:  +34 91 384 09 10 

Polska 
AbbVie Polska Sp. z o.o. 
Tel.: +48 22 372 78 00 

France 
AbbVie 
Tél: +33 (0) 1 45 60 13 00 

Portugal 
AbbVie, Lda.  
Tel: +351 (0)21 1908400

Hrvatska  
AbbVie d.o.o. 
Tel + 385 (0)1 5625 501

România 
AbbVie S.R.L. 
Tel: +40 21 529 30 35

Ireland 
AbbVie Limited  
Tel: +353 (0)1 4287900

Slovenija 
AbbVie Biofarmacevtska družba d.o.o. 
Tel: +386 (1)32 08 060

Ísland 
Vistor hf. 
Tel: +354 535 7000 

Slovenská republika 
AbbVie s.r.o. 
Tel: +421 2 5050 0777

Italia 
AbbVie S.r.l.  
Tel: +39 06 928921 

Suomi/Finland 
AbbVie Oy  
Puh/Tel:  +358 (0)10 2411 200 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Τηλ.: +357 22 34 74 40

Sverige 
AbbVie AB 
Tel:  +46 (0)8 684 44 600

Latvija 
AbbVie SIA  
Tel: +371 67605000 

United Kingdom 
AbbVie Ltd  
Tel: +44 (0)1628 561090

 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 



343 

To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the 
local representative of the Marketing Authorisation Holder. 
 
 
7. Injecting Humira 
 

 The following instructions explain how to give your child a subcutaneous injection of Humira 
using the pre-filled syringe. First read all the instructions carefully and then follow them step by 
step.  
 

 You will be instructed by your doctor, nurse or pharmacist on the technique of injection.  
 

 Do not attempt to inject your child until you are sure that you understand how to prepare and give 
the injection.  
 

 After proper training, the injection can be given by your child or given by another person, for 
example, a family member or friend.   
 

 Only use each pre-filled syringe for one injection. 
 
Humira Pre-filled Syringe 
 
           Plunger             Finger Grip         Needle Cover 

 
 

Do not use the pre-filled syringe and call your doctor or pharmacist if the 
 

 liquid is cloudy, discoloured, or has flakes or particles in it 
 expiry (EXP) date has passed 
 liquid has been frozen or left in direct sunlight 
 pre-filled syringe has been dropped or crushed 

 
Do not remove the needle cover until just before injection. Keep Humira out of the sight and reach 
of children. 
 

STEP 1 
 
Take Humira out of the refrigerator. 
 
Leave Humira at room temperature for 15 to 30 minutes before injecting. 
 

 Do not remove the needle cover while allowing Humira to reach room temperature 
 Do not warm Humira in any other way. For example, do not warm it in a microwave or in hot 

water 



344 

STEP 2  

           Syringe 

 
                 Pad 

Check the expiry (EXP) date. Do not use the pre-filled 
syringe if expiry (EXP) date has passed. 
 
Place the following on a clean, flat surface 
 

 1 single-use pre-filled syringe and  
 1 alcohol pad 

 
Wash and dry your hands. 

STEP 3 
 
Injectable Areas 

     Injectable Areas 

Choose an injection site: 
 

 On the front of your child’s thighs or 
 Your child’s belly (abdomen) at least 5 cm from 

his/her belly button (navel) 
 At least 3 cm from your child’s last injection site 

 
Wipe the injection site in a circular motion with the alcohol 
pad. 
 

 Do not inject through clothes 
 Do not inject into skin that is sore, bruised, red, 

hard, scarred, has stretch marks, or areas with 
psoriasis plaques 



345 

STEP 4 

 

Hold the pre-filled syringe in one hand. 
 
Check the liquid in the pre-filled syringe. 
 

 Make sure the liquid is clear and colourless 
 Do not use the pre-filled syringe if the liquid is 

cloudy or has particles 
 Do not use the pre-filled syringe if it has been 

dropped or crushed 
 

Gently pull the needle cover straight off with the other hand. 
Throw the needle cover away. Do not recap. 
 

 Do not touch the needle with your fingers or let the 
needle touch anything 

STEP 5 

 

Hold the pre-filled syringe with the needle facing up. 
 

 Hold the pre-filled syringe at eye level with one 
hand so you can see the air in the pre-filled syringe 

 
Slowly push the plunger in to push the air out through the 
needle.  
 

 It is normal to see a drop of liquid at the end of the 
needle 

 

STEP 6 Hold the body of the pre-filled syringe in one hand between 
the thumb and index fingers, like you would a pencil. 
 
Squeeze the skin at your child’s injection site with your 
other hand to make a raised area and hold it firmly. 

 



346 

STEP 7 

 

Insert the needle all the way into the skin at about a 
45-degree angle with one quick, short motion. 
 

 After the needle is in, let go of the skin you are 
holding  

 
Slowly push the plunger all the way in until all of the liquid 
is injected and the pre-filled syringe is empty. 
 

STEP 8 

 
              Cotton Ball 

When the injection is completed, slowly pull the needle out 
of the skin while keeping the pre-filled syringe at the same 
angle. 
 
After completing the injection, place a cotton ball or gauze 
pad on the skin over the injection site. 
 

 Do not rub 
 Slight bleeding at the injection site is normal 

 

 
STEP 9 
 
Throw away the used pre-filled syringe in a special disposal container as instructed by your doctor, 
nurse or pharmacist. Never recap a needle. 
 

 Do not recycle or throw the pre-filled syringe in the household waste 
 Always keep the pre-filled syringe and the special disposal container out of the sight and 

reach of children 
 

The needle cover, alcohol pad, cotton ball or gauze pad, blister and packaging may be put in your 
household waste. 

  



347 

Package leaflet: Information for the patient 
 

Humira 40 mg/0.8 ml solution for injection 
adalimumab 

 
Read all of this leaflet carefully before your child starts using this medicine because it contains 
important information. 
 Keep this leaflet. You may need to read it again. 
 Your doctor will also give you a Patient Reminder Card, which contains important safety 

information that you need to be aware of before your child is given Humira and during treatment 
with Humira. Keep this Patient Reminder Card with you or your child. 

 If you have any further questions, please ask your doctor or pharmacist. 
 This medicine has been prescribed for your child only. Do not pass it on to others. It may harm 

them, even if their signs of illness are the same as your child's. 
 If your child gets any side effects, talk to your child’s doctor or pharmacist. This includes any 

possible side effects not listed in this leaflet (see section 4). 
 
What is in this leaflet 
1. What Humira is and what it is used for 
2. What you need to know before your child uses Humira 
3. How to use Humira 
4. Possible side effects 
5. How to store Humira 
6. Contents of the pack and other information 
 
 
1. What Humira is and what it is used for 
Humira contains the active substance adalimumab. 
 
Humira is intended for the treatment of the inflammatory diseases described below: 

 Polyarticular juvenile idiopathic arthritis 
 Enthesitis-related arthritis 
 Paediatric plaque psoriasis 
 Adolescent hidradenitis suppurativa 
 Paediatric Crohn’s disease 
 Paediatric ulcerative colitis 
 Paediatric uveitis 

 
The active ingredient in Humira, adalimumab, is a human monoclonal antibody. Monoclonal antibodies 
are proteins that attach to a specific target. 
 
The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the 
immune (defence) system and is present at increased levels in the inflammatory diseases listed above. By 
attaching to TNFα, Humira decreases the process of inflammation in these diseases. 
 
Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis 
 
Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis are inflammatory diseases. 
 
Humira is used to treat polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis. Your child 
may first be given other disease-modifying medicines, such as methotrexate. If these medicines do not 



348 

work well enough, your child will be given Humira to treat his/her polyarticular juvenile idiopathic 
arthritis or enthesitis-related arthritis. 
 
Paediatric plaque psoriasis 
 
Plaque psoriasis is a skin condition that causes red, flaky, crusty patches of skin covered with silvery 
scales. Plaque psoriasis can also affect the nails, causing them to crumble, become thickened and lift away 
from the nail bed which can be painful. Psoriasis is believed to be caused by a problem with the body’s 
immune system that leads to an increased production of skin cells. 
 
Humira is used to treat severe plaque psoriasis in children and adolescents aged 4 to 17 years in whom 
topical therapy and phototherapies have either not worked very well or are not suitable.   
 
Adolescent hidradenitis suppurativa 
 
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic and often painful inflammatory skin 
disease. Symptoms may include tender nodules (lumps) and abscesses (boils) that may leak pus. It most 
commonly affects specific areas of the skin, such as under the breasts, the armpits, inner thighs, groin and 
buttocks. Scarring may also occur in affected areas. 
 
Humira is used to treat hidradenitis suppurativa in adolescents from 12 years of age. Humira can reduce 
the number of nodules and abscesses you have and the pain that is often associated with the disease. You 
may first be given other medicines. If you do not respond well enough to these medicines, you will be 
given Humira. 
 
Paediatric Crohn's disease  
 
Crohn’s disease is an inflammatory disease of the digestive tract. Humira is indicated for the treatment of 
Crohn's disease in children aged 6 to 17 years. Your child may first be given other medicines. If these 
medicines do not work well enough, your child will be given Humira to reduce the signs and symptoms of 
his/her disease. 
 
Paediatric ulcerative colitis  
 
Ulcerative colitis is an inflammatory disease of the large intestine. Humira is used to treat moderate to 
severe ulcerative colitis in children aged 6 to 17 years. Your child may first be given other medicines. If 
these medicines do not work well enough, your child will be given Humira to reduce the signs and 
symptoms of his/her disease. 
 
Paediatric uveitis 
 
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. 
 
Humira is used to treat children from 2 years of age with chronic non-infectious uveitis with inflammation 
affecting the front of the eye. This inflammation may lead to a decrease of vision and/or the presence of 
floaters in the eye (black dots or wispy lines that move across the field of vision). Humira works by 
reducing this inflammation. 
 
 
2. What you need to know before your child uses Humira 
 
Do not use Humira  
 



349 

 If your child is allergic to adalimumab or any of the other ingredients of this medicine (listed in 
section 6).  

 
 If your child has a severe infection, including active tuberculosis (see “Warnings and 

precautions”). It is important that you tell your doctor if your child has symptoms of infections, 
e.g. fever, wounds, feeling tired, dental problems. 
 

 If your child has moderate or severe heart failure. It is important to tell your doctor if your child 
has had or has a serious heart condition (see “Warnings and precautions”). 

 
Warnings and precautions 
 
Talk to your child’s doctor or pharmacist before using Humira 
 

 If your child experiences allergic reactions with symptoms such as chest tightness, wheezing, 
dizziness, swelling or rash do not inject more Humira and contact your doctor immediately since, 
in rare cases, these reactions can be life threatening. 
 

 If your child has an infection, including long-term or localized infection (for example, leg ulcer) 
consult your doctor before starting Humira. If you are unsure, contact your doctor.  
 

 Your child might get infections more easily while receiving Humira treatment. This risk may 
increase if his/her lung function is impaired. These infections may be serious and include 
tuberculosis, infections caused by viruses, fungi, parasites or bacteria, or other opportunistic 
infections and sepsis that may, in rare cases, be life-threatening. It is important to tell your doctor 
if your child gets symptoms such as fever, wounds, feeling tired or dental problems. Your doctor 
may recommend temporary discontinuation of Humira. 
 

 As cases of tuberculosis have been reported in patients treated with Humira, your doctor will 
check your child for signs and symptoms of tuberculosis before starting Humira. This will include 
a thorough medical evaluation including your child’s medical history and appropriate screening 
tests (for example chest X-ray and a tuberculin test). The conduct and results of these tests should 
be recorded on your child's Patient Reminder Card. It is very important that you tell your doctor 
if your child has ever had tuberculosis, or if he/she has been in close contact with someone who 
has had tuberculosis. Tuberculosis can develop during therapy even if your child has received 
preventative treatment for tuberculosis. If symptoms of tuberculosis (persistent cough, weight 
loss, listlessness, mild fever), or any other infection appear during or after therapy tell your doctor 
immediately. 

 
 Advise your doctor if your child resides or travels in regions where fungal infections such as 

histoplasmosis, coccidioidomycosis or blastomycosis are endemic. 
 

 Advise your doctor if your child has a history of recurrent infections or other conditions that 
increase the risk of infections. 

 
 Advise your doctor if your child is a carrier of the hepatitis B virus (HBV), if he/she has active 

HBV or if you think he/she might be at risk of contracting HBV. Your child’s doctor should test 
your child for HBV. Humira can cause reactivation of HBV in people who carry this virus. In 
some rare cases, especially if your child is taking other medicines that suppress the immune 
system, reactivation of HBV can be life-threatening.  
 



350 

 It is important to tell your doctor if your child gets symptoms of infections, such as fever, wounds, 
feeling tired or dental problems. 
 

 If your child is about to undergo surgery or dental procedures please inform your doctor that 
he/she is taking Humira. Your doctor may recommend temporary discontinuation. 
 

 If your child has or develops a demyelinating disease such as multiple sclerosis, your doctor will 
decide if he/she should receive or continue to receive Humira. Tell your doctor immediately if 
your child experiences symptoms like changes in vision, weakness in arms or legs or numbness or 
tingling in any part of the body. 

 
 Certain vaccines may cause infections and should not be given while receiving Humira.  Please 

check with your doctor before your child receives any vaccines. It is recommended that children, 
if possible, be brought up to date with all immunisations in agreement with current immunisation 
guidelines prior to initiating Humira therapy. If you received Humira while you were pregnant, 
your baby may be at higher risk for getting such an infection for up to approximately five months 
after the last dose you received during pregnancy. It is important that you tell your baby's doctors 
and other health care professionals about your Humira use during your pregnancy so they can 
decide when your baby should receive any vaccine. 
 

 If your child has mild heart failure and is being treated with Humira, his/her heart failure status 
must be closely monitored by your doctor.  It is important to tell your doctor if your child has had 
or has a serious heart condition.  If he/she develops new or worsening symptoms of heart failure 
(e.g. shortness of breath, or swelling of his/her feet), you must contact your doctor immediately. 
Your doctor will decide if your child should receive Humira.   
 

 In some patients the body may fail to produce enough of the blood cells that help your child's 
body fight infections or help him/her to stop bleeding.  If your child develops a fever that does not 
go away, bruises or bleeds very easily or looks very pale, call your doctor right away. Your doctor 
may decide to stop treatment. 

 
 There have been very rare cases of certain kinds of cancer in children and adult patients taking 

Humira or other TNF blockers. People with more serious rheumatoid arthritis that have had the 
disease for a long time may have a higher than average risk of getting lymphoma (a cancer that 
affects the lymph system) and leukemia (a cancer that affects the blood and bone marrow). If your 
child takes Humira the risk of getting lymphoma, leukemia, or other cancers may increase. On 
rare occasions, a specific and severe type of lymphoma, has been observed in patients taking 
Humira. Some of those patients were also treated with azathioprine or 6- mercaptopurine. Tell 
your doctor if your child is taking azathioprine or 6-mercaptopurine with Humira. In addition 
cases of non-melanoma skin cancer have been observed in patients taking Humira. If new skin 
lesions appear during or after therapy or if existing lesions change appearance, tell your doctor. 

 
 There have been cases of cancers, other than lymphoma in patients with a specific type of lung 

disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another TNF blocker. 
If your child has COPD, or is a heavy smoker, you should discuss with your doctor whether 
treatment with a TNF blocker is appropriate for your child. 
 

 On rare occasions, treatment with Humira could result in lupus-like syndrome. Contact your 
doctor if symptoms such as persistent unexplained rash, fever, joint pain or tiredness occur. 

 
Other medicines and Humira 
 



351 

Tell your child’s doctor or pharmacist if your child is taking, has recently taken or might take any other 
medicines. 
 
Humira can be taken together with methotrexate or certain disease-modifying anti-rheumatic agents 
(sulfasalazine, hydroxychloroquine, leflunomide and injectable gold preparations), steroids or pain 
medications including non-steroidal anti-inflammatory drugs (NSAIDs). 
 
Your child should not take Humira with medicines containing the active substances anakinra or abatacept 
due to increased risk of serious infection. If you have questions, please ask your doctor. 
 
Pregnancy and breast-feeding 
 

 Your child should consider the use of adequate contraception to prevent pregnancy and continue 
its use for at least 5 months after the last Humira treatment. 

 If your child is pregnant, thinks she may be pregnant or is planning to have a baby, ask her doctor 
for advice about taking this medicine. 

 Humira should only be used during a pregnancy if needed. 
 According to a pregnancy study, there was no higher risk of birth defects when the mother had 

received Humira during pregnancy compared with mothers with the same disease who did not 
receive Humira. 

 Humira can be used during breast-feeding. 
 If your child receives Humira during her pregnancy, her baby may have a higher risk for getting 

an infection. 
 It is important that you tell her baby’s doctor and other health care professionals about her Humira 

use during her pregnancy before the baby receives any vaccine. For more information on vaccines, 
see the “Warnings and precautions” section. 

 
Driving and using machines 
 
Humira may have a minor influence on the ability to drive, cycle or use machines. Room spinning 
sensation and vision disturbances may occur after taking Humira. 
 
Humira contains sodium 
 
This medicinal product contains less than 1 mmol of sodium (23 mg) per 0.8 ml dose, i.e. essentially 
‘sodium-free’. 
 
 
3. How to use Humira 
 
Always use this medicine exactly as your child’s doctor or pharmacist has instructed. Check with your 
child’s doctor or pharmacist if you are not sure about any of the instructions or if you have any questions. 
Your doctor may prescribe another strength of Humira if your child needs a different dose. 
 
Children and adolescents with polyarticular juvenile idiopathic arthritis 
 
Children and adolescents from 2 years of age weighing 10 kg to less than 30 kg 
 
The recommended dose of Humira is 20 mg every other week. 
 
Children and adolescents from 2 years of age weighing 30 kg or more 
 
The recommended dose of Humira is 40 mg every other week. 



352 

 
Children, adolescents and adults with enthesitis-related arthritis 
 
Children and adolescents from 6 years of age weighing 15 kg to less than 30 kg 
 
The recommended dose of Humira is 20 mg every other week. 
 
Children, adolescents and adults from 6 years of age weighing 30 kg or more 
 
The recommended dose of Humira is 40 mg every other week. 
 
Children and adolescents with psoriasis 
 
Children and adolescents from 4 to 17 years of age weighing 15 kg to less than 30 kg 
 
The recommended dose of Humira is an initial dose of 20 mg, followed by 20 mg one week later. 
Thereafter, the usual dose is 20 mg every other week. 
 
Children and adolescents from 4 to 17 years of age weighing 30 kg or more 
 
The recommended dose of Humira is an initial dose of 40 mg, followed by 40 mg one week later. 
Thereafter, the usual dose is 40 mg every other week. 
 
Adolescents with hidradenitis suppurativa from 12 to 17 years of age, weighing 30 kg or more 
 
The recommended dose of Humira is an initial dose of 80 mg (as two 40 mg injections in one day), 
followed by 40 mg every other week starting one week later. If you have an inadequate response to 
Humira 40 mg every other week, your doctor may increase the dosage to 40 mg every week or 80 mg 
every other week. 
 
It is recommended that you use an antiseptic wash daily on the affected areas. 
 
Children and adolescents with Crohn's disease 
 
Children and adolescents from 6 to 17 years of age weighing less than 40 kg   
 
The usual dose regimen is 40 mg initially followed by 20 mg two weeks later. If a faster response is 
required, your child’s doctor may prescribe an initial dose of 80 mg (as two 40 mg injections in one day) 
followed by 40 mg two weeks later. 
 
Thereafter, the usual dose is 20 mg every other week. Depending on your child’s response, your child’s 
doctor may increase the dose frequency to 20 mg every week.   
 
Children and adolescents from 6 to 17 years of age weighing 40 kg or more  
 
The usual dose regimen is 80 mg (as two 40 mg injections in one day) initially followed by 40 mg two 
weeks later. If a faster response is required, your child’s doctor may prescribe an initial dose of 160 mg 
initially (as four 40 mg injections in one day or two 40 mg injections per day for two consecutive days) 
followed by 80 mg (as two 40 mg injections in one day) two weeks later. 
 
Thereafter, the usual dose is 40 mg every other week. Depending on your child’s response, your child’s 
doctor may increase the dosage to 40 mg every week or 80 mg every other week. 
 



353 

Children and adolescents with ulcerative colitis 
 
Children and adolescents from 6 years of age weighing less than 40 kg 
 
The usual Humira dose is 80 mg (as two 40 mg injections in one day) initially followed by 40 mg (as one 
40 mg injection) two weeks later. Thereafter, the usual dose is 40 mg every other week.  
 
Patients who turn 18 years of age while on 40 mg every other week, should continue their prescribed dose. 
 
Children and adolescents from 6 years of age weighing 40 kg or more 
 
The usual Humira dose is 160 mg (as four 40 mg injections in one day or two 40 mg injections per day for 
two consecutive days) initially, followed by 80 mg (as two 40 mg injections in one day) two weeks later. 
Thereafter the usual dose is 80 mg every other week.  
 
Patients who turn 18 years of age while on 80 mg every other week, should continue their prescribed dose. 
 
Children and adolescents with chronic non-infectious uveitis from 2 years of age 
 
Children and adolescents from 2 years of age weighing less than 30 kg 
The usual dose of Humira is 20 mg every other week with methotrexate. 
 
Your child’s doctor may also prescribe an initial dose of 40 mg which may be administered one week 
prior to the start of the usual dose. 
 
Children and adolescents from 2 years of age weighing 30 kg or more 
 
The usual dose of Humira is 40 mg every other week with methotrexate. 
 
Your child’s doctor may also prescribe an initial dose of 80 mg which may be administered one week 
prior to the start of the usual dose. 
 
Method and route of administration 
 
Humira is administered by injection under the skin (by subcutaneous injection). 
 
Instructions for preparing and giving an injection of Humira 
 
The following instructions explain how to inject Humira. Please read the instructions carefully and follow 
them step by step. You will be instructed by your child's doctor or his/her assistant on the technique of 
injection and the amount to give to your child. Do not attempt to give your child an injection until you are 
sure that you understand how to prepare and give the injection. After proper training, the injection can be 
self-administered or given by another person, for example a family member or friend. 
 
Failure to perform the following steps as described may cause contamination which may lead to infection 
of your child. 
 
This injection should not be mixed in the same syringe or vial with any other medicine. 
 
1)  Setting up  
 
 Make sure you know the proper amount (volume) needed for dosing. If you don’t know the amount, 

STOP HERE and contact your doctor for further instruction. 



354 

 
 You will need a special container for waste, such as a sharps container or as instructed by your 

nurse, doctor or pharmacist. Place the container on your work surface. 
 
 Wash your hands thoroughly 

 
 Remove one box containing, one syringe, one vial adapter, one vial, two alcohol pads and one 

needle from the carton. If there is a second box in the carton for a future injection, place it back in 
the refrigerator immediately. 
 

 Look at the expiry date on the box to be used. DO NOT use any item after the date shown on the 
box. 
  

 Set up the following items on a clean surface, DO NOT take them out of their individual packaging 
yet. 

 
o One 1 ml syringe (1)  
o One vial adapter (2)  
o One vial for paediatric use of Humira for injection (3) 
o Two alcohol pads (4) 
o One needle (5) 

   

 
 

 Humira is a liquid that is clear and colourless. DO NOT use if the liquid is cloudy, discoloured or 
has flakes or particles in it. 

 
2)  Preparing the Humira dose for injection  
 
 General handling: DO NOT dispose of any waste items until after the injection is completed. 
 
 Prepare the needle by partially peeling the package open from the end closest to the yellow syringe 

connector. Peel the package just far enough to expose the yellow syringe connector.  
Set the package down with the clear side of the package facing up. 

 



355 

 
 

 
 Pop off the white plastic cap from the vial to see the top of the vial stopper. 
 

 
 
 Use one of the alcohol pads to wipe the vial stopper. DO NOT touch the vial stopper after wiping 

with the alcohol pad. 
 
 Peel the cover off the vial adapter package but do not take out the vial adapter.    
 

 
 
 Hold the vial with the vial stopper facing up. 
 
 With the vial adapter still in the clear package, attach it to the vial stopper by pushing down until the 

vial adapter snaps in place.   
 
 When you are sure the adapter is attached to the vial, lift off the package from the vial adapter.  
 



356 

 Gently set the vial with vial adapter down on your clean work surface. Be careful that it does not fall 
over. DO NOT touch the vial adapter.  

 

 
 

 Prepare the syringe by partially peeling the package open from the end closest to white plunger rod. 
 

 Peel the clear package just far enough to expose the white plunger rod, but do not take the syringe 
out of the package.   

 
 Hold the syringe package and SLOWLY pull the white plunger rod out to 0.1 ml beyond the 

prescribed dose (For example, if the prescribed dose is 0.5 ml, pull the white plunger rod to 0.6 ml). 
NEVER pull past the 0.9 ml position regardless of prescribed dose. 

 
 You will set the volume to the prescribed dose in a later step. 
 
 DO NOT pull the white plunger rod completely out of the syringe. 
 
NOTE:  
 
If the white plunger rod is pulled completely out of the syringe, discard the syringe and contact your 
Humira provider for a replacement. DO NOT try to reinsert the white plunger rod. 
 

 
 
 
 
 
 
 
 
Dose + 0.1 ml 

 
 DO NOT use the white plunger rod to remove the syringe from the package. Hold the syringe on 

the graduated area and pull the syringe from its package. DO NOT set the syringe down at any 
time. 

 
 While holding the vial adapter firmly, insert the syringe tip into the vial adapter and twist the 

syringe clockwise with one hand until firm. DO NOT over-tighten.  



357 

 

 
 
 While holding the vial, push the white plunger rod all the way down. This step is important to get 

the proper dose. Hold the white plunger rod in and turn the vial and syringe upside down. 
 

 
 

 SLOWLY pull the white plunger rod out to 0.1 ml beyond the prescribed dose. This is important to 
get the proper dose. You will set the volume to the prescribed dose in step 4, Dose Preparation. If 
the prescribed dose is 0.5 ml, pull the white plunger rod out to 0.6 ml. You will see the liquid 
medication from the vial go into the syringe. 

 

 
 

 Push the white plunger rod all the way back in to push the liquid medication back into the vial. 
Again, SLOWLY pull the white plunger rod out to 0.1 ml beyond the prescribed dose, this is 
important to get the proper dose and important in order to prevent air bubbles or air gaps in the 
liquid medication. You will set the volume to the prescribed dose in step 4, Dose Preparation. 

 



358 

 
 
 If you see remaining air bubbles or air gaps in the liquid medication in the syringe, you may repeat 

this process up to 3 times. DO NOT shake the syringe. 
 

 
NOTE:  
 
If the white plunger rod is pulled completely out of the syringe, discard the syringe and contact your 
Humira provider for a replacement. DO NOT try to reinsert the white plunger rod. 
 
 While still holding the syringe upright at the graduated area, remove the vial adapter with the vial by 

twisting the vial adapter off with the other hand. Be sure to remove the vial adapter with the vial 
from the syringe. DO NOT touch the tip of the syringe. 

 

 
 
 If a large air bubble or air gap can be seen near the syringe tip, SLOWLY push the white plunger 

rod into the syringe until fluid begins to enter the syringe tip. DO NOT push the white plunger rod 
past the dose position. 

 
 For example, if the prescribed dose is 0.5 ml, DO NOT push the white plunger rod past the 0.5 ml 

position. 
 
 Check to see that the fluid remaining in the syringe is at least the prescribed dose volume. If the 

remaining volume is less than the prescribed dose volume, DO NOT use the syringe and contact 
your healthcare provider. 

 
 With your free hand, pick up the needle package with the yellow syringe connector facing down. 
 
 Keeping the syringe up, insert the syringe tip into the yellow syringe connector and twist the syringe 

as indicated by the arrow in the picture until firm. The needle is now attached to the syringe. 



359 

 

 
 

 Pull the needle package off, but DO NOT remove the clear needle cap. 
 
 Place the syringe on your clean work surface. Continue with injection site and dose preparation 

immediately. 
 

3)  Choosing and preparing an injection site 
 
 Choose a site on your thigh or stomach. DO NOT use the same site that was used for the last 

injection. 
 The new injection site should be given at least 3 cm from the last injection site. 
 

 
 

 DO NOT inject in an area where the skin is reddened, bruised, or hard. This may mean there is an 
infection and therefore you should contact your doctor. 

 To reduce the chance of infection, wipe the injection site with the other alcohol pad. DO NOT touch 
the area again before injecting. 
 

4)  Dose Preparation  

 
 Pick up the syringe with the needle pointing up. 
 Use your other hand to flip the pink needle cover down toward the syringe. 



360 

 

  
 

 Remove the clear needle cap by pulling it straight up with your other hand. 
 

 
 

 The needle is clean. 
 DO NOT touch the needle. 
 DO NOT set the syringe down at any time after the clear needle cap is off. 
 DO NOT try to put the clear needle cap back on the needle. 
 
 Hold the syringe at eye-level with the needle pointing up to see the amount clearly. Be careful not 

to squirt the liquid medication into your eye. 
 Recheck the prescribed medication amount. 
 Push the white plunger rod gently into the syringe until the syringe contains the prescribed amount 

of liquid. Excess liquid may come out of the needle while the white plunger rod is being pushed. DO 
NOT wipe off the needle or the syringe. 

 
5)  Injecting Humira 
 
 With the free hand, gently grasp the cleaned area of skin and hold firmly.  
 With the other hand, hold syringe at 45-degree angle to skin.  
 With one quick, short motion, push needle all the way into skin. 
 Let go of the skin in your hand. 
 Push the white plunger rod to inject the liquid medication until the syringe is empty. 
 When the syringe is empty, remove the needle from skin, being careful to pull it out at the same 

angle as when it was inserted. 



361 

 
 
 Gently flip the pink needle cover up, over the needle and snap into place and set the syringe with 

needle on the work surface. DO NOT put the clear needle cap back on the needle. 
 

 
 
 Using a piece of gauze, apply pressure over the injection site for 10 seconds. A little bleeding may 

occur. DO NOT rub the injection site. Use a plaster if you want to.  
 
6)  Throwing away supplies 

 
 You will need a special container for waste, such as a sharps container or as instructed by your nurse, 

doctor or pharmacist. 
 Put the syringe with needle, vial and vial adapter into a special sharps container. DO NOT put these 

items into regular household waste. 
 The syringe, needle, vial and vial adapter MUST NEVER be reused. 
 Keep the special container out of the sight and reach of children at all times. 
 Throw away all other used items into your regular household waste. 
 
If you use more Humira than you should 
 
If you accidentally inject a larger amount of Humira liquid, or if you inject Humira more frequently than 
told to by your doctor, call your doctor and tell him/her that your child has taken more. Always take the 
outer carton or the vial of the medicine with you, even if it is empty.  
 
If you use less Humira than you should 
 
If you accidentally inject a smaller amount of Humira liquid, or if you inject Humira less frequently than 
told to by your child’s doctor or pharmacist, you should call your child’s doctor or pharmacist and tell 
him/her that your child has taken less. Always take the outer carton or the vial of the medicine with you, 
even if it is empty. 



362 

 
If you forget to use Humira 
 
If you forget to give your child a Humira injection, you should inject the Humira dose as soon as you 
remember. Then administer your child's next dose as you would have on the originally scheduled day, had 
you not forgotten a dose.  
 
If your child stops using Humira 
 
The decision to stop using Humira should be discussed with your child’s doctor. Your child’s symptoms 
may return upon discontinuation. 
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side 
effects are mild to moderate. However, some may be serious and require treatment. Side effects may occur 
at least up to 4 months after the last Humira injection.   
 
Tell your doctor immediately if you notice any of the following 
 
 severe rash, hives or other signs of allergic reaction;  
 swollen face, hands, feet; 
 trouble breathing, swallowing; 
 shortness of breath with exertion or upon lying down or swelling of the feet. 
 
Tell your doctor as soon as possible if you notice any of the following 
 
 signs of infection such as fever, feeling sick, wounds, dental problems, burning on urination; 
 feeling weak or tired; 
 coughing; 
 tingling; 
 numbness; 
 double vision; 
 arm or leg weakness; 
 a bump or open sore that doesn't heal; 
 signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, 

paleness. 
 
The symptoms described above can be signs of the below listed side effects, which have been observed 
with Humira. 
 
Very common (may affect more than 1 in 10 people) 
 
 injection site reactions (including pain, swelling, redness or itching); 
 respiratory tract infections (including cold, runny nose, sinus infection, pneumonia); 
 headache; 
 abdominal pain; 
 nausea and vomiting; 
 rash; 



363 

 musculoskeletal pain. 
 

Common (may affect up to 1 in 10 people)  
 
 serious infections (including blood poisoning and influenza); 
 intestinal infections (including gastroenteritis); 
 skin infections (including cellulitis and shingles); 
 ear infections; 
 oral infections (including tooth infections and cold sores); 
 reproductive tract infections; 
 urinary tract infection; 
 fungal infections; 
 joint infections, 
 benign tumours; 
 skin cancer; 
 allergic reactions (including seasonal allergy); 
 dehydration; 
 mood swings (including depression); 
 anxiety; 
 difficulty sleeping; 
 sensation disorders such as tingling, prickling or numbness; 
 migraine; 
 nerve root compression (including low back pain and leg pain); 
 vision disturbances;  
 eye inflammation; 
 inflammation of the eye lid and eye swelling; 
 vertigo; 
 sensation of heart beating rapidly; 
 high blood pressure; 
 flushing; 
 haematoma; 
 cough; 
 asthma; 
 shortness of breath; 
 gastrointestinal bleeding; 
 dyspepsia (indigestion, bloating, heart burn); 
 acid reflux disease; 
 sicca syndrome (including dry eyes and dry mouth); 
 itching; 
 itchy rash; 
 bruising; 
 inflammation of the skin (such as eczema); 
 breaking of finger nails and toe nails; 
 increased sweating; 
 hair loss; 
 new onset or worsening of psoriasis; 
 muscle spasms; 
 blood in urine; 
 kidney problems; 
 chest pain; 



364 

 oedema; 
 fever; 
 reduction in blood platelets which increases risk of bleeding or bruising; 
 impaired healing. 
 
Uncommon (may affect up to 1 in 100 people) 
 
 opportunistic infections (which include tuberculosis and other infections that occur when resistance 

to disease is lowered); 
 neurological infections (including viral meningitis); 
 eye infections; 
 bacterial infections; 
 diverticulitis (inflammation and infection of the large intestine); 
 cancer;  
 cancer that affects the lymph system; 
 melanoma; 
 immune disorders that could affect the lungs, skin and lymph nodes ( most commonly presenting as 

sarcoidosis); 
 vasculitis (inflammation of blood vessels); 
 tremor; 
 stroke; 
 neuropathy; 
 hearing loss, buzzing; 
 sensation of heart beating irregularly such as skipped beats; 
 heart problems that can cause shortness of breath or ankle swelling; 
 heart attack; 
 a sac in the wall of a major artery, inflammation and clot of a vein; blockage of a blood vessel; 
 lung diseases causing shortness of breath (including inflammation); 
 pulmonary embolism (blockage in an artery of the lung); 
 pleural effusion (abnormal collection of fluid on the pleural space); 
 inflammation of the pancreas which causes severe pain in the abdomen and back; 
 difficulty in swallowing; 
 facial oedema; 
 gallbladder inflammation, gallbladder stones; 
 fatty liver; 
 night sweats; 
 scar; 
 abnormal muscle breakdown; 
 systemic lupus erythematosus (including inflammation of skin, heart, lung, joints and other organ 

systems); 
 sleep interruptions; 
 impotence; 
 inflammations. 
 
Rare (may affect up to 1 in 1000 people) 
 
 leukemia (cancer affecting the blood and bone marrow); 
 severe allergic reaction with shock; 
 multiple sclerosis; 
 nerve disorders (such as eye nerve inflammation and Guillain-Barré syndrome that may cause 

muscle weakness, abnormal sensations, tingling in the arms and upper body); 



365 

 heart stops pumping; 
 pulmonary fibrosis (scarring of the lung); 
 intestinal perforation; 
 hepatitis; 
 reactivation of hepatitis B; 
 autoimmune hepatitis (inflammation of the liver caused by the body's own immune system); 
 cutaneous vasculitis (inflammation of blood vessels in the skin); 
 Stevens-Johnson syndrome (early symptoms include malaise, fever, headache and rash); 
 facial oedema associated with allergic reactions; 
 erythema multiforme (inflammatory skin rash); 
 lupus-like syndrome; 
 angioedema (localized swelling of the skin); 
 lichenoid skin reaction (itchy reddish-purple skin rash). 
 
Not known (frequency cannot be estimated from available data) 
 
 hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal); 
 Merkel cell carcinoma (a type of skin cancer); 
 Kaposi’s sarcoma, a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma 

most commonly appears as purple lesions on the skin; 
 liver failure; 
 worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle         

weakness). 
 
Some side effects observed with Humira may not have symptoms and may only be discovered through 
blood tests. These include: 
 
Very common (may affect more than 1 in 10 people) 
 
 low blood measurements for white blood cells; 
 low blood measurements for red blood cells; 
 increased lipids in the blood; 
 elevated liver enzymes. 
 
Common (may affect up to 1 in 10 people) 
 
 high blood measurements for white blood cells;   
 low blood measurements for platelets; 
 increased uric acid in the blood; 
 abnormal blood measurements for sodium; 
 low blood measurements for calcium; 
 low blood measurements for phosphate; 
 high blood sugar; 
 high blood measurements for lactate dehydrogenase; 
 autoantibodies present in the blood; 
 low blood potassium. 
 
Uncommon (may affect up to 1 in 100 people)  
 
 elevated bilirubin measurement (liver blood test). 
 



366 

Rare (may affect up to 1 in 1,000 people) 
 
 low blood measurements for white blood cells, red blood cells and platelet count. 

 
Reporting of side effects 
If your child gets any side effects, talk to your child’s doctor or pharmacist. This includes any possible 
side effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects, you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Humira 
 
Keep this medicine out of the sight and reach of children.  
 
Do not use this medicine after the expiry date stated on the label/blister/carton after EXP.  
 
Store in a refrigerator (2C – 8C). Do not freeze.  
 
Keep the vial in the outer carton in order to protect from light. 
 
Do not throw away any medicines via wastewater or household waste. Ask your doctor or pharmacist how 
to throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Humira contains 
 
The active substance is adalimumab. 
The other ingredients are mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen phosphate 
dihydrate, disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and water 
for injections. 
 
What the Humira vial looks like and contents of the pack 
 
Humira 40 mg solution for injection in vials is supplied as a sterile solution of 40 mg adalimumab 
dissolved in 0.8 ml solution. 
 
The Humira vial is a glass vial containing a solution of adalimumab. One pack contains 2 boxes, each 
containing 1 vial, 1 empty sterile syringe, 1 needle, 1 vial adapter and 2 alcohol pads. 
 
Humira may be available as a vial, a pre-filled syringe and/or a pre-filled pen. 
 
Marketing Authorisation Holder 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 



367 

Manufacturer  
 
AbbVie Biotechnology GmbH 
Max-Planck-Ring 2 
D – 65205 Wiesbaden 
Germany 
 
and 
 
AbbVie Biotechnology GmbH 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder. 
 
België/Belgique/Belgien 
AbbVie SA 
Tél/Tel: +32 10  477811 

Lietuva 
AbbVie UAB  
Tel: +370 5 205 3023 

България 
АбВи ЕООД 
Тел.:+359 2 90 30 430 

Luxembourg/Luxemburg 
AbbVie SA 
Belgique/Belgien 
Tél/Tel: +32 10 477811

Česká republika 
AbbVie s.r.o.  
Tel: +420 233 098 111 

Magyarország 
AbbVie Kft. 
Tel.:+36 1 455 8600

Danmark 
AbbVie A/S 
Tlf: +45 72 30-20-28 

Malta 
V.J.Salomone Pharma Limited  
Tel: +356 22983201

Deutschland 
AbbVie Deutschland GmbH & Co. KG 
Tel: 00800 222843 33 (gebührenfrei) 
Tel: +49 (0) 611 / 1720-0

Nederland 
AbbVie B.V. 
Tel:  +31 (0)88 322 2843 

Eesti 
AbbVie Biopharmaceuticals GmbH Eesti filiaal  
Tel: +372 623 1011 

Norge 
AbbVie AS 
Tlf: +47 67 81 80 00

Ελλάδα 
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. 
Τηλ: +30 214 4165 555 

Österreich 
AbbVie GmbH  
Tel: +43 1 20589-0 

España 
AbbVie Spain, S.L.U. 
Tel:  +34 91 384 09 10 

Polska 
AbbVie Polska Sp. z o.o. 
Tel.: +48 22 372 78 00 

France 
AbbVie 
Tél: +33 (0) 1 45 60 13 00 

Portugal 
AbbVie, Lda.  
Tel: +351 (0)21 1908400 

Hrvatska  
AbbVie d.o.o. 
Tel + 385 (0)1 5625 501

România 
AbbVie S.R.L. 
Tel: +40 21 529 30 35

Ireland 
AbbVie Limited  
Tel: +353 (0)1 4287900

Slovenija 
AbbVie Biofarmacevtska družba d.o.o. 
Tel: +386 (1)32 08 060



368 

Ísland 
Vistor hf. 
Tel: +354 535 7000 

Slovenská republika 
AbbVie s.r.o. 
Tel: +421 2 5050 0777

Italia 
AbbVie S.r.l.  
Tel: +39 06 928921 

Suomi/Finland 
AbbVie Oy  
Puh/Tel:  +358 (0)10 2411 200 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Τηλ.: +357 22 34 74 40

Sverige 
AbbVie AB 
Tel:  +46 (0)8 684 44 600

Latvija 
AbbVie SIA  
Tel: +371 67605000 

United Kingdom 
AbbVie Ltd  
Tel: +44 (0)1628 561090

 
This leaflet was last revised in  
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 

 
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the 
local representative of the Marketing Authorisation Holder. 

  



369 

Package leaflet: Information for the patient 
 

Humira 40 mg solution for injection in pre-filled syringe 
adalimumab 

 
Read all of this leaflet carefully before you start using this medicine because it contains important 
information for you. 
 Keep this leaflet. You may need to read it again. 
 Your doctor will also give you a Patient Reminder Card, which contains important safety 

information that you need to be aware of before you are given Humira and during treatment with 
Humira. Keep this Patient Reminder Card with you.  

 If you have any further questions, please ask your doctor or pharmacist. 
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even 

if their signs of illness are the same as yours. 
 If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet (see section 4). 
 
What is in this leaflet  
1. What Humira is and what it is used for 
2. What you need to know before you use Humira 
3. How to use Humira 
4. Possible side effects 
5 How to store Humira 
6. Contents of the pack and other information 
 
 
1. What Humira is and what it is used for 
 
Humira contains the active substance adalimumab.  
 
Humira is intended for the treatment of the inflammatory diseases described below: 
 Rheumatoid arthritis,  
 Polyarticular juvenile idiopathic arthritis,  
 Enthesitis-related arthritis,  
 Ankylosing spondylitis,  
 Axial spondyloarthritis without radiographic evidence of ankylosing spondylitis,  
 Psoriatic arthritis,  
 Psoriasis, 
 Hidradenitis suppurativa,  
 Crohn’s disease,  
 Ulcerative colitis and  
 Non-infectious uveitis 
 
The active ingredient in Humira, adalimumab, is a human monoclonal antibody. Monoclonal antibodies 
are proteins that attach to a specific target. 
 
The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the 
immune (defence) system and is present at increased levels in the inflammatory diseases listed above. By 
attaching to TNFα, Humira decreases the process of inflammation in these diseases. 
 



370 

Rheumatoid arthritis 
 
Rheumatoid arthritis is an inflammatory disease of the joints. 
 
Humira is used to treat rheumatoid arthritis in adults. If you have moderate to severe active rheumatoid 
arthritis, you may first be given other disease-modifying medicines, such as methotrexate. If you do not 
respond well enough to these medicines, you will be given Humira to treat your rheumatoid arthritis.   
 
Humira can also be used to treat severe, active and progressive rheumatoid arthritis without previous 
methotrexate treatment. 
 
Humira has been shown to slow down the damage to the cartilage and bone of the joints caused by the 
disease and to improve physical function. 
 
Usually, Humira is used with methotrexate. If your doctor determines that methotrexate is inappropriate, 
Humira can be given alone. 
 
Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis 
 
Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis are inflammatory diseases. 
 
Humira is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged 2 to 17 
years and enthesitis-related arthritis in children and adolescents aged 6 to 17 years. You may first be given 
other disease-modifying medicines, such as methotrexate. If you do not respond well enough to these 
medicines, you will be given Humira to treat your polyarticular juvenile idiopathic arthritis or enthesitis-
related arthritis. 
 
Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing 
spondylitis 
 
Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing 
spondylitis, are inflammatory diseases of the spine. 
 
Humira is used to treat ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of 
ankylosing spondylitis in adults. If you have ankylosing spondylitis or axial spondyloarthritis without 
radiographic evidence of ankylosing spondylitis, you will first be given other medicines. If you do not 
respond well enough to these medicines, you will be given Humira to reduce the signs and symptoms of 
your disease. 
 
Psoriatic arthritis 
 
Psoriatic arthritis is an inflammation of the joints associated with psoriasis. 
 
Humira is used to treat psoriatic arthritis in adults. Humira has been shown to slow down the damage to 
the cartilage and bone of the joints caused by the disease and to improve physical function. 
 
Plaque psoriasis in adults and children  
 
Plaque psoriasis is a skin condition that causes red, flaky, crusty patches of skin covered with silvery 
scales. Plaque psoriasis can also affect the nails, causing them to crumble, become thickened and lift away 
from the nail bed which can be painful. Psoriasis is believed to be caused by a problem with the body’s 
immune system that leads to an increased production of skin cells. 
 



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Humira is used to treat moderate to severe plaque psoriasis in adults. Humira is also used to treat severe 
plaque psoriasis in children and adolescents aged 4 to 17 years for whom topical therapy and 
phototherapies have either not worked very well or are not suitable. 
 
Hidradenitis suppurativa in adults and adolescents 
 
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic and often painful inflammatory skin 
disease. Symptoms may include tender nodules (lumps) and abscesses (boils) that may leak pus. It most 
commonly affects specific areas of the skin, such as under the breasts, the armpits, inner thighs, groin and 
buttocks. Scarring may also occur in affected areas. 
 
Humira is used to treat hidradenitis suppurativa in adults and adolescents from 12 years of age. Humira 
can reduce the number of nodules and abscesses you have and the pain that is often associated with the 
disease. You may first be given other medicines. If you do not respond well enough to these medicines, 
you will be given Humira. 
 
Crohn’s disease in adults and children 
 
Crohn’s disease is an inflammatory disease of the digestive tract. 
 
Humira is used to treat Crohn’s disease in adults and children aged 6 to 17 years. If you have Crohn’s 
disease you will first be given other medicines. If you do not respond well enough to these medicines, you 
will be given Humira to reduce the signs and symptoms of your Crohn’s disease. 
 
Ulcerative colitis in adults and children 
 
Ulcerative colitis is an inflammatory disease of the large intestine. 
 
Humira is used to treat moderate to severe ulcerative colitis in adults and children aged 6 to 17 years. If 
you have ulcerative colitis you may first be given other medicines. If you do not respond well enough to 
these medicines, you will be given Humira to reduce the signs and symptoms of your disease. 
 
Non-infectious uveitis in adults and children 
 
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. 
 
Humira is used to treat  

 Adults with non-infectious uveitis with inflammation affecting the back of the eye 
 Children from 2 years of age with chronic non-infectious uveitis with inflammation affecting the 

front of the eye  
 
This inflammation may lead to a decrease of vision and/or the presence of floaters in the eye (black dots or 
wispy lines that move across the field of vision). Humira works by reducing this inflammation. 
 
 
2. What you need to know before you use Humira 
 
Do not use Humira 
 

 If you are allergic to adalimumab or any of the other ingredients of this medicine (listed in section 
6).  

 



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 If you have a severe infection, including active tuberculosis (see Warnings and precautions”). It is 
important that you tell your doctor if you have symptoms of infections, e.g. fever, wounds, feeling 
tired, dental problems. 

 
 If you have moderate or severe heart failure. It is important to tell your doctor if you have had or 

have a serious heart condition (see “Warnings and precautions”). 
 
Warnings and precautions 
 
Talk to your doctor or pharmacist before using Humira 
 

 If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, 
swelling or rash do not inject more Humira and contact your doctor immediately since, in rare 
cases, these reactions can be life threatening.  
 

 If you have an infection, including long-term or localized infection (for example, leg ulcer) 
consult your doctor before starting Humira. If you are unsure, contact your doctor.  
 

 You might get infections more easily while you are receiving Humira treatment. This risk may 
increase if your lung function is impaired. These infections may be serious and include 
tuberculosis, infections caused by viruses, fungi, parasites or bacteria, or other opportunistic 
infections and sepsis that may, in rare cases, be life-threatening. It is important to tell your doctor 
if you get symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may 
recommend temporary discontinuation of Humira. 

 
 As cases of tuberculosis have been reported in patients treated with Humira, your doctor will 

check you for signs and symptoms of tuberculosis before starting Humira. This will include a 
thorough medical evaluation including your medical history and appropriate screening tests (for 
example chest X-ray and a tuberculin test). The conduct and results of these tests should be 
recorded on your Patient Reminder Card. It is very important that you tell your doctor if you 
have ever had tuberculosis, or if you have been in close contact with someone who has had 
tuberculosis. Tuberculosis can develop during therapy even if you have received preventative 
treatment for tuberculosis. If symptoms of tuberculosis (persistent cough, weight loss, listlessness, 
mild fever), or any other infection appear during or after therapy tell your doctor immediately.  
 

 Advise your doctor if you reside or travel in regions where fungal infections such as 
histoplasmosis, coccidioidomycosis or blastomycosis are endemic. 

 
 Advise your doctor if you have a history of recurrent infections or other conditions that increase 

the risk of infections. 
 

 Advise your doctor if you are a carrier of the hepatitis B virus (HBV), if you have active HBV or 
if you think you might be at risk of contracting HBV. Your doctor should test you for HBV. 
Humira can cause reactivation of HBV in people who carry this virus. In some rare cases, 
especially if you are taking other medicines that suppress the immune system, reactivation of 
HBV can be life-threatening.  

 
 If you are over 65 years you may be more susceptible to infections while taking Humira. You and 

your doctor should pay special attention to signs of infection while you are being treated with 
Humira. It is important to tell your doctor if you get symptoms of infections, such as fever, 
wounds, feeling tired or dental problems. 

 



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 If you are about to undergo surgery or dental procedures, please inform your doctor that you are 
taking Humira. Your doctor may recommend temporary discontinuation of Humira. 

 
 If you have or develop demyelinating disease such as multiple sclerosis, your doctor will decide if 

you should receive or continue to receive Humira. Tell your doctor immediately if you experience 
symptoms like changes in your vision, weakness in your arms or legs or numbness or tingling in 
any part of your body. 

 
 Certain vaccines may cause infections and should not be given while receiving Humira. Please 

check with your doctor before you receive any vaccines. It is recommended that children, if 
possible, be brought up to date with all immunisations in agreement with current immunisation 
guidelines prior to initiating Humira therapy. If you received Humira while you were pregnant, 
your baby may be at higher risk for getting such an infection for up to approximately five months 
after the last dose you received during pregnancy. It is important that you tell your baby's doctors 
and other health care professionals about your Humira use during your pregnancy so they can 
decide when your baby should receive any vaccine. 

 
 If you have mild heart failure and you are being treated with Humira, your heart failure status 

must be closely monitored by your doctor. It is important to tell your doctor if you have had or 
have a serious heart condition. If you develop new or worsening symptoms of heart failure (e.g. 
shortness of breath, or swelling of your feet), you must contact your doctor immediately. Your 
doctor will decide if you should receive Humira. 

 
 In some patients the body may fail to produce enough of the blood cells that help your body fight 

infections or help you to stop bleeding. If you develop a fever that does not go away, bruise or 
bleed very easily or look very pale, call your doctor right away. Your doctor may decide to stop 
treatment. 

 
 There have been very rare cases of certain kinds of cancer in children and adult patients taking 

Humira or other TNF blockers. People with more serious rheumatoid arthritis that have had the 
disease for a long time may have a higher than average risk of getting lymphoma (a cancer that 
affects the lymph system) and leukemia (a cancer that affects the blood and bone marrow). If you 
take Humira the risk of getting lymphoma, leukemia, or other cancers may increase. On rare 
occasions, a specific and severe type of lymphoma has been observed in patients taking Humira. 
Some of those patients were also treated with azathioprine or 6- mercaptopurine. Tell your doctor 
if you are taking azathioprine or 6-mercaptopurine with Humira. In addition, cases of non-
melanoma skin cancer have been observed in patients taking Humira. If new skin lesions appear 
during or after therapy or if existing lesions change appearance, tell your doctor. 

 
 There have been cases of cancers, other than lymphoma in patients with a specific type of lung 

disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another TNF blocker. 
If you have COPD, or are a heavy smoker, you should discuss with your doctor whether treatment 
with a TNF blocker is appropriate for you.  
 

 On rare occasions, treatment with Humira could result in lupus-like syndrome. Contact your 
doctor if symptoms such as persistent unexplained rash, fever, joint pain or tiredness occur. 

 
Children and adolescents 
 

 Vaccinations: if possible, children should be up to date with all vaccinations before using Humira. 
 Do not give Humira to children with polyarticular juvenile idiopathic arthritis below the age of 2 

years. 
 



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Other medicines and Humira 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 
 
Humira can be taken together with methotrexate or certain disease-modifying anti-rheumatic agents 
(sulfasalazine, hydroxychloroquine, leflunomide and injectable gold preparations), steroids or pain 
medications including non-steroidal anti-inflammatory drugs (NSAIDs). 
 
You should not take Humira with medicines containing the active substances anakinra or abatacept due to 
increased risk of serious infection. If you have questions, please ask your doctor.  
 
Pregnancy and breast-feeding 
 

 You should consider the use of adequate contraception to prevent pregnancy and continue its use 
for at least 5 months after the last Humira treatment. 

 If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for 
advice about taking this medicine. 

 Humira should only be used during a pregnancy if needed. 
 According to a pregnancy study, there was no higher risk of birth defects when the mother had 

received Humira during pregnancy compared with mothers with the same disease who did not 
receive Humira. 

 Humira can be used during breast-feeding 
 If you receive Humira during your pregnancy, your baby may have a higher risk for getting an 

infection. 
 It is important that you tell your baby’s doctors and other health care professionals about your 

Humira use during your pregnancy before the baby receives any vaccine (for more information on 
vaccines see the “Warnings and precautions” section). 

 
Driving and using machines 
 
Humira may have a minor influence on your ability to drive, cycle or use machines. Room spinning 
sensation and vision disturbances may occur after taking Humira. 
 
Humira contains sodium 
 
This medicinal product contains less than 1 mmol of sodium (23 mg) per 0.8 ml dose, i.e. essentially 
‘sodium-free’. 
 
 
3. How to use Humira 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are not sure. Your doctor may prescribe another strength of Humira if you need a 
different dose. 
 
Adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or axial spondyloarthritis 
without radiographic evidence of ankylosing spondylitis 
 
Humira is injected under the skin (subcutaneous use). The usual dose for adults with rheumatoid arthritis, 
ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of ankylosing spondylitis 
and for patients with psoriatic arthritis is 40 mg adalimumab given every other week as a single dose.   
 



375 

In rheumatoid arthritis, methotrexate is continued while using Humira. If your doctor determines that 
methotrexate is inappropriate, Humira can be given alone.  
 
If you have rheumatoid arthritis and you do not receive methotrexate with your Humira therapy, your 
doctor may decide to give 40 mg adalimumab every week or 80 mg every other week. 
 
Children, adolescents and adults with polyarticular juvenile idiopathic arthritis 
 
Children and adolescents from 2 years of age weighing 10 kg to less than 30 kg 
 
The recommended dose of Humira is 20 mg every other week. 
 
Children, adolescents and adults from 2 years of age weighing 30 kg or more 
 
The recommended dose of Humira is 40 mg every other week. 
 
Children, adolescents and adults with enthesitis-related arthritis 
 
Children and adolescents from 6 years of age weighing 15 kg to less than 30 kg 
 
The recommended dose of Humira is 20 mg every other week. 
 
Children, adolescents and adults from 6 years of age weighing 30 kg or more 
 
The recommended dose of Humira is 40 mg every other week. 
 
Adults with psoriasis 
 
The usual dose for adults with psoriasis is an initial dose of 80 mg (as two 40 mg injections in one day), 
followed by 40 mg given every other week starting one week after the initial dose. You should continue to 
inject Humira for as long as your doctor has told you. Depending on your response, your doctor may 
increase the dosage to 40 mg every week or 80 mg every other week. 
 
Children and adolescents with plaque psoriasis 
 
Children and adolescents from 4 to 17 years of age weighing 15 kg to less than 30 kg 
 
The recommended dose of Humira is an initial dose of 20 mg, followed by 20 mg one week later. 
Thereafter, the usual dose is 20 mg every other week. 
 
Children and adolescents from 4 to 17 years of age weighing 30 kg or more 
 
The recommended dose of Humira is an initial dose of 40 mg, followed by 40 mg one week later. 
Thereafter, the usual dose is 40 mg every other week. 
 
Adults with hidradenitis suppurativa 
 
The usual dose regimen for hidradenitis suppurativa is an initial dose of 160 mg (as four 40 mg injections 
in one day or two 40 mg injections per day for two consecutive days), followed by an 80 mg dose (as two 
40 mg injections in one day) two weeks later. After two further weeks, continue with a dose of 40 mg 
every week or 80 mg every other week, as prescribed by your doctor. It is recommended that you use an 
antiseptic wash daily on the affected areas. 
 



376 

Adolescents with hidradenitis suppurativa from 12 to 17 years of age weighing 30 kg or more 
 
The recommended dose of Humira is an initial dose of 80 mg (as two 40 mg injections in one day), 
followed by 40 mg every other week starting one week later. If you have an inadequate response to 
Humira 40 mg every other week, your doctor may increase the dosage to 40 mg every week or 80 mg 
every other week. 
 
It is recommended that you use an antiseptic wash daily on the affected areas. 
 
Adults with Crohn’s disease 
 
The usual dose regimen for Crohn’s disease is 80 mg (as two 40 mg injections in one day) initially 
followed by 40 mg every other week two weeks later. If  a faster response is required your doctor may 
prescribe an initial dose of 160 mg (as four 40 mg injections in one day or two 40 mg injections per day 
for two consecutive days), followed by 80 mg (as two 40 mg injections in one day) two weeks later and 
thereafter as 40 mg every other week. Depending on your response, your doctor may increase the dosage 
to 40 mg every week or 80 mg every other week. 
 
Children and adolescents with Crohn's disease 
 
Children and adolescents from 6 to 17 years of age weighing less than 40 kg   
 
The usual dose regimen is 40 mg initially followed by 20 mg two weeks later. If a faster response is 
required, your doctor may prescribe an initial dose of 80 mg (as two 40 mg injections in one day) 
followed by 40 mg two weeks later. 
 
Thereafter, the usual dose is 20 mg every other week. Depending on your response, your doctor may 
increase the dose frequency to 20 mg every week.   
 
Children and adolescents from 6 to 17 years of age weighing 40 kg or more 
The usual dose regimen is 80 mg (as two 40 mg injections in one day) initially followed by 40 mg two 
weeks later. If a faster response is required, your doctor may prescribe an initial dose of 160 mg (as four 
40 mg injections in one day or as two 40 mg injections per day for two consecutive days) followed by 
80 mg (as two 40 mg injections in one day) two weeks later. 
 
Thereafter, the usual dose is 40 mg every other week. Depending on your response, your doctor may 
increase the dosage to 40 mg every week or 80 mg every other week. 
 
Adults with ulcerative colitis 
 
The usual Humira dose for adults with ulcerative colitis is 160 mg (as four 40 mg injections in one day or 
two 40 mg injections per day for two consecutive days) at Week 0 and 80 mg (as two 40 mg injections in 
one day) at Week 2 and thereafter 40 mg every other week. Depending on your response, your doctor may 
increase the dosage to 40 mg every week or 80 mg every other week.  
 
Children and adolescents with ulcerative colitis 
 
Children and adolescents from 6 years of age weighing less than 40 kg 
 
The usual Humira dose is 80 mg (as two 40 mg injections in one day) initially followed by 40 mg (as one 
40 mg injection) two weeks later. Thereafter, the usual dose is 40 mg every other week.  
 
Patients who turn 18 years of age while on 40 mg every other week, should continue their prescribed dose. 



377 

 
Children and adolescents from 6 years of age weighing 40 kg or more 
 
The usual Humira dose is 160 mg (as four 40 mg injections in one day or two 40 mg injections per day for 
two consecutive days) initially, followed by 80 mg (as two 40 mg injections in one day) two weeks later. 
Thereafter the usual dose is 80 mg every other week.  
 
Patients who turn 18 years of age while on 80 mg every other week, should continue their prescribed dose. 
 
Adults with non-infectious uveitis 
 
The usual dose for adults with non-infectious uveitis is an initial dose of 80 mg (as two injections in one 
day), followed by 40 mg given every other week starting one week after the initial dose. You should 
continue to inject Humira for as long as your doctor has told you. 
 
In non-infectious uveitis, corticosteroids or other medicines that influence the immune system may be 
continued while using Humira. Humira can also be given alone. 
 
Children and adolescents with chronic non-infectious uveitis from 2 years of age 
 
Children and adolescents from 2 years of age weighing less than 30 kg 
 
The usual dose of Humira is 20 mg every other week with methotrexate. 
 
Your doctor may also prescribe an initial dose of 40 mg which may be administered one week prior to the 
start of the usual dose. 
 
Children and adolescents from 2 years of age weighing 30 kg or more 
 
The usual dose of Humira is 40 mg every other week with methotrexate. 
 
Your doctor may also prescribe an initial dose of 80 mg which may be administered one week prior to the 
start of the usual dose. 
 
Method and route of administration 
 
Humira is administered by injection under the skin (by subcutaneous injection). 
 
Instructions for preparing and giving an injection of Humira 
 
The following instructions explain how to inject Humira. Please read the instructions carefully and follow 
them step by step. You will be instructed by your doctor or his/her assistant on the technique of self-
injection. Do not attempt to self-inject until you are sure that you understand how to prepare and give the 
injection. After proper training, the injection can be self-administered or given by another person, for 
example a family member or friend.   
 
This injection should not be mixed in the same syringe or vial with any other medicine. 
 
1)  Setting up 
 
Wash your hands thoroughly  
Set up the following items on a clean surface 
 



378 

o One pre-filled syringe of Humira for injection      
o One alcohol pad 

 

 
 
Look at the expiry date on the syringe. Do not use the product after the month and year shown. 
 
2) Choosing and preparing an injection site  
 
Choose a site on your thigh or stomach 
 

 
 

Each new injection should be given at least 3 cm from the last injection site.  
o Do not inject in an area where the skin is reddened, bruised, or hard. This may mean there is 

an infection. 
o Wipe the injection site with the enclosed alcohol pad, using a circular motion. 
o Do not touch the area again before injecting. 

 
3)  Injecting Humira  
 
• Do NOT shake the syringe. 
• Remove cap from needle syringe, being careful not to touch the needle or let it touch any surface. 
• With one hand, gently grasp the cleaned areas of skin and hold firmly 
 



379 

 
 
 With the other hand, hold syringe at 45-degree angle to skin, with the grooved side up. 
 With one quick, short motion, push needle all the way into skin 
 Release the skin with the first hand 
 Push plunger to inject solution – it can take from 2 to 5 seconds to empty the syringe 
 When the syringe is empty, remove the needle from skin, being careful to keep it at the same angle 

as when it was inserted 
 Using your thumb or a piece of gauze, apply pressure over the injection site for 10 seconds.  A little 

bleeding may occur. Do not rub the injection site. Use a plaster if you want to. 
 
4)  Throwing away supplies 
 
 The Humira syringe should NEVER be reused. NEVER recap a needle. 
 After injecting Humira, immediately throw away the used syringe in a special container as 

instructed by your doctor, nurse or pharmacist. 
 Keep this container out of the sight and reach of children 
 
Instructions for preparing and giving an injection of Humira 
 
The following instructions explain how to inject Humira. Please read the instructions carefully and follow 
them step by step. You will be instructed by your doctor or his/her assistant on the technique of self-
injection. Do not attempt to self-inject until you are sure that you understand how to prepare and give the 
injection. After proper training, the injection can be self-administered or given by another person, for 
example a family member or friend. 
 
This injection should not be mixed in the same syringe or vial with any other medicine. 
 
1)  Setting up 
 
Wash your hands thoroughly  
Set up the following items on a clean surface 
 

o One pre-filled syringe of Humira for injection 
o One alcohol pad 

 



380 

 
 

Look at the expiry date on the syringe. Do not use the product after the month and year shown.  
 
2)  Choosing and preparing an injection site  
 
Choose a site on your thigh or stomach 
 

 
 
Each new injection should be given at least 3 cm from the last injection site.  

o Do not inject in an area where the skin is reddened, bruised, or hard. This may mean there is 
an infection. 

o Wipe the injection site with the enclosed alcohol pad, using a circular motion. 
o Do not touch the area again before injecting. 

 
3)  Injecting Humira  
 
 Do NOT shake the syringe. 
 Remove cap from needle syringe, being careful not to touch the needle or let it touch any surface. 
 With one hand, gently grasp the cleaned areas of skin and hold firmly 
 

 
 
 With the other hand, hold syringe at 45-degree angle to skin, with the grooved side up. 
 With one quick, short motion, push needle all the way into skin 



381 

 Release the skin with the first hand 
 Push plunger to inject solution – it can take from 2 to 5 seconds to empty the syringe 
 When the syringe is empty, remove the needle from skin, being careful to keep it at the same angle 

as when it was inserted 
 Hold the syringe in one hand and with the other hand slide the outer protective shield over the 

exposed needle until it locks in place 
 Using your thumb or a piece of gauze, apply pressure over the injection site for 10 seconds.  A little 

bleeding may occur. Do not rub the injection site. Use a plaster if you want to. 
 
4) Throwing away supplies 
 
 The Humira syringe should NEVER be reused. NEVER recap a needle 
 After injecting Humira, immediately throw away the used syringe in a special container as 

instructed by your doctor, nurse or pharmacist. 
Keep this container out of the sight and reach of children 
 
If you use more Humira than you should 
 
If you accidentally inject Humira more frequently than told to by your doctor or pharmacist, call your 
doctor or pharmacist and tell him/her that you have taken more. Always take the outer carton of the 
medicine with you, even if it is empty.  
 
If you forget to use Humira 
 
If you forget to give yourself an injection, you should inject the next dose of Humira as soon as you 
remember. Then take your next dose as you would have on your originally scheduled day, had you not 
forgotten a dose.  
 
If you stop using Humira 
 
The decision to stop using Humira should be discussed with your doctor. Your symptoms may return upon 
discontinuation. 
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side 
effects are mild to moderate. However, some may be serious and require treatment. Side effects may occur 
at least up to 4 months after the last Humira injection.   
 
Tell your doctor immediately if you notice any of the following  
 severe rash, hives or other signs of allergic reaction;  
 swollen face, hands, feet; 
 trouble breathing, swallowing; 
 shortness of breath with exertion or upon lying down or swelling of the feet. 
 
Tell your doctor as soon as possible if you notice any of the following  
 signs of infection such as fever, feeling sick, wounds, dental problems, burning on urination; 
 feeling weak or tired; 
 coughing; 



382 

 tingling; 
 numbness; 
 double vision; 
 arm or leg weakness; 
 a bump or open sore that doesn't heal; 
 signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, 

paleness. 
 
The symptoms described above can be signs of the below listed side effects, which have been observed 
with Humira. 
 
Very common (may affect more than 1 in 10 people)   
 
 injection site reactions (including pain, swelling, redness or itching); 
 respiratory tract infections (including cold, runny nose, sinus infection, pneumonia); 
 headache; 
 abdominal pain; 
 nausea and vomiting; 
 rash; 
 musculoskeletal pain. 
 
Common (may affect up to 1 in 10 people) 
 
 serious infections (including blood poisoning and influenza); 
 intestinal infections (including gastroenteritis); 
 skin infections (including cellulitis and shingles); 
 ear infections; 
 oral infections (including tooth infections and cold sores); 
 reproductive tract infections; 
 urinary tract infection; 
 fungal infections; 
 joint infections; 
 benign tumours; 
 skin cancer; 
 allergic reactions (including seasonal allergy); 
 dehydration; 
 mood swings (including depression); 
 anxiety; 
 difficulty sleeping; 
 sensation disorders such as tingling, prickling or numbness; 
 migraine; 
 nerve root compression (including low back pain and leg pain); 
 vision disturbances;  
 eye inflammation; 
 inflammation of the eye lid and eye swelling; 
 vertigo; 
 sensation of heart beating rapidly; 
 high blood pressure; 
 flushing; 
 haematoma; 
 cough; 



383 

 asthma; 
 shortness of breath; 
 gastrointestinal bleeding; 
 dyspepsia (indigestion, bloating, heart burn); 
 acid reflux disease; 
 sicca syndrome (including dry eyes and dry mouth); 
 itching; 
 itchy rash; 
 bruising; 
 inflammation of the skin (such as eczema); 
 breaking of finger nails and toe nails; 
 increased sweating; 
 hair loss; 
 new onset or worsening of psoriasis; 
 muscle spasms; 
 blood in urine; 
 kidney problems; 
 chest pain; 
 oedema; 
 fever; 
 reduction in blood platelets which increases risk of bleeding or bruising; 
 impaired healing. 
 
Uncommon (may affect up to 1 in 100 people) 
 
 opportunistic infections (which include tuberculosis and other infections that occur when resistance 

to disease is lowered); 
 neurological infections (including viral meningitis); 
 eye infections; 
 bacterial infections; 
 diverticulitis (inflammation and infection of the large intestine); 
 cancer; 
 cancer that affects the lymph system; 
 melanoma; 
 immune disorders that could affect the lungs, skin and lymph nodes (most commonly presenting as 

sarcoidosis); 
 vasculitis (inflammation of blood vessels); 
 tremor; 
 neuropathy; 
 stroke; 
 hearing loss, buzzing; 
 sensation of heart beating irregularly such as skipped beats; 
 heart problems that can cause shortness of breath or ankle swelling; 
 heart attack; 
 a sac in the wall of a major artery, inflammation and clot of a vein; blockage of a blood vessel; 
 lung diseases causing shortness of breath (including inflammation); 
 pulmonary embolism (blockage in an artery of the lung); 
 pleural effusion (abnormal collection of fluid in the pleural space); 
 inflammation of the pancreas which causes severe pain in the abdomen and back; 
 difficulty in swallowing; 



384 

 facial oedema; 
 gallbladder inflammation, gallbladder stones; 
 fatty liver; 
 night sweats; 
 scar; 
 abnormal muscle breakdown; 
 systemic lupus erythematosus (including inflammation of skin, heart, lung, joints and other organ 

systems); 
 sleep interruptions; 
 impotence; 
 inflammations. 
 
Rare (may affect up to 1 in 1,000 people) 
 
 leukaemia (cancer affecting the blood and bone marrow); 
 Severe allergic reaction with shock; 
 multiple sclerosis; 
 nerve disorders (such as eye nerve inflammation and Guillain-Barré syndrome that may cause 

muscle weakness, abnormal sensations, tingling in the arms and upper body); 
 heart stops pumping;  
 pulmonary fibrosis (scarring of the lung); 
 intestinal perforation; 
 hepatitis; 
 reactivation of hepatitis B; 
 autoimmune hepatitis (inflammation of the liver caused by the body's own immune system); 
 cutaneous vasculitis (inflammation of blood vessels in the skin); 
 Stevens-Johnson syndrome (early symptoms include malaise, fever, headache and rash); 
 facial oedema associated with allergic reactions; 
 erythema multiforme (inflammatory skin rash); 
 lupus-like syndrome; 
 angioedema (localized swelling of the skin); 
 lichenoid skin reaction (itchy reddish-purple skin rash). 
 
Not known (frequency cannot be estimated from available data) 
 
 hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal); 
 Merkel cell carcinoma (a type of skin cancer); 
 Kaposi’s sarcoma, a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma 

most commonly appears as purple lesions on the skin; 
 liver failure; 
 worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle         

weakness). 
 
Some side effects observed with Humira may not have symptoms and may only be discovered through 
blood tests. These include: 
 
Very common (may affect more than 1 in 10 people)  
 
 low blood measurements for white blood cells; 
 low blood measurements for red blood cells; 
 increased lipids in the blood; 



385 

 elevated liver enzymes. 
 
Common (may affect up to 1 in 10 people) 
 
 high blood measurements for white blood cells;   
 low blood measurements for platelets; 
 increased uric acid in the blood; 
 abnormal blood measurements for sodium; 
 low blood measurements for calcium; 
 low blood measurements for phosphate; 
 high blood sugar; 
 high blood measurements for lactate dehydrogenase; 
 autoantibodies present in the blood; 
 low blood potassium. 
 
Uncommon (may affect up to 1 in 100 people)  
  
 elevated bilirubin measurement (liver blood test). 
 
Rare (may affect up to 1 in 1,000 people) 
 
 low blood measurements for white blood cells, red blood cells and platelet count. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects, you can help provide more information on the safety of this 
medicine. 
 
 
5. How to store Humira 
 
Keep this medicine out of the sight and reach of children.  
 
Do not use this medicine after the expiry date stated on the label/blister/carton after EXP.  
 
Store in a refrigerator (2C – 8C). Do not freeze.  
 
Keep the pre-filled syringe in the outer carton in order to protect from light.   
 
Alternative Storage: 
 
When needed (for example when you are travelling), a single Humira pre-filled syringe may be stored at 
room temperature (up to 25°C) for a maximum period of 14 days – be sure to protect it from light. Once 
removed from the refrigerator for room temperature storage, the syringe must be used within 14 days or 
discarded, even if it is returned to the refrigerator.   
 
You should record the date when the syringe is first removed from refrigerator and the date after which it 
should be discarded.   
 
Do not throw away any medicines via wastewater or household waste. Ask your doctor or pharmacist how 
to throw away medicines you no longer use. These measures will help protect the environment. 



386 

 
 
6. Contents of the pack and other information 
 
What Humira contains 
 
The active substance is adalimumab. 
The other ingredients are mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen phosphate 
dihydrate, disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and water 
for injections. 
 
What the Humira pre-filled syringe looks like and contents of the pack 
 
Humira 40 mg solution for injection in pre-filled syringe is supplied as a sterile solution of 40 mg 
adalimumab dissolved in 0.8 ml solution. 
 
The Humira pre-filled syringe is a glass syringe containing a solution of adalimumab. Each pack contains 
1, 2, 4 or 6 pre-filled syringes for patient use with 1, 2, 4 or 6 alcohol pads, respectively.   
 
Not all pack sizes may be marketed. 
 
Humira may be available as a vial, a pre-filled syringe and/or a pre-filled pen. 
 
Marketing Authorisation Holder 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
Manufacturer 
 
AbbVie Biotechnology GmbH  
Max-Planck-Ring 2 
D - 65205 Wiesbaden 
Germany 
 
and 
 
AbbVie Biotechnology GmbH 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder. 
 
België/Belgique/Belgien 
AbbVie SA 
Tél/Tel: +32 10  477811 

Lietuva 
AbbVie UAB  
Tel: +370 5 205 3023 

България 
АбВи ЕООД 
Тел.:+359 2 90 30 430 

Luxembourg/Luxemburg 
AbbVie SA 
Belgique/Belgien



387 

Tél/Tel: +32 10 477811
Česká republika 
AbbVie s.r.o.  
Tel: +420 233 098 111 

Magyarország 
AbbVie Kft. 
Tel.:+36 1 455 8600

Danmark 
AbbVie A/S 
Tlf: +45 72 30-20-28 

Malta 
V.J.Salomone Pharma Limited  
Tel: +356 22983201

Deutschland 
AbbVie Deutschland GmbH & Co. KG 
Tel: 00800 222843 33 (gebührenfrei) 
Tel: +49 (0) 611 / 1720-0

Nederland 
AbbVie B.V. 
Tel:  +31 (0)88 322 2843 

Eesti 
AbbVie Biopharmaceuticals GmbH Eesti filiaal  
Tel: +372 623 1011 

Norge 
AbbVie AS 
Tlf: +47 67 81 80 00

Ελλάδα 
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. 
Τηλ: +30 214 4165 555 

Österreich 
AbbVie GmbH  
Tel: +43 1 20589-0 

España 
AbbVie Spain, S.L.U. 
Tel:  +34 91 384 09 10 

Polska 
AbbVie Polska Sp. z o.o. 
Tel.: +48 22 372 78 00 

France 
AbbVie 
Tél: +33 (0) 1 45 60 13 00 

Portugal 
AbbVie, Lda.  
Tel: +351 (0)21 1908400

Hrvatska  
AbbVie d.o.o. 
Tel + 385 (0)1 5625 501

România 
AbbVie S.R.L. 
Tel: +40 21 529 30 35

Ireland 
AbbVie Limited  
Tel: +353 (0)1 4287900

Slovenija 
AbbVie Biofarmacevtska družba d.o.o. 
Tel: +386 (1)32 08 060

Ísland 
Vistor hf. 
Tel: +354 535 7000 

Slovenská republika 
AbbVie s.r.o. 
Tel: +421 2 5050 0777

Italia 
AbbVie S.r.l.  
Tel: +39 06 928921 

Suomi/Finland 
AbbVie Oy  
Puh/Tel:  +358 (0)10 2411 200 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Τηλ.: +357 22 34 74 40

Sverige 
AbbVie AB 
Tel:  +46 (0)8 684 44 600

Latvija 
AbbVie SIA  
Tel: +371 67605000 

United Kingdom 
AbbVie Ltd  
Tel: +44 (0)1628 561090

 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the 
local representative of the Marketing Authorisation Holder. 
  



388 

Package leaflet: Information for the patient 
 

Humira 40 mg solution for injection in pre-filled pen 
adalimumab 

 
Read all of this leaflet carefully before you start using this medicine because it contains important 
information for you. 
 Keep this leaflet. You may need to read it again. 
 Your doctor will also give you a Patient Reminder Card, which contains important safety 

information that you need to be aware of before you are given Humira and during treatment with 
Humira. Keep this Patient Reminder Card with you. 

 If you have any further questions, ask your doctor or pharmacist. 
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even 

if their signs of illness are the same as yours. 
 If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet (see section 4). 
 
What is in this leaflet  
1. What Humira is and what it is used for 
2. What you need to know before you use Humira 
3. How to use Humira 
4. Possible side effects 
5 How to store Humira 
6. Contents of the pack and other information 
 
 
1. What Humira is and what it is used for 
 
Humira contains the active substance adalimumab.  
 
Humira is intended for the treatment of the inflammatory diseases described below: 
 Rheumatoid arthritis,  
 Polyarticular juvenile idiopathic arthritis,  
 Enthesitis-related arthritis,  
 Ankylosing spondylitis,  
 Axial spondyloarthritis without radiographic evidence of ankylosing spondylitis,  
 Psoriatic arthritis,  
 Psoriasis, 
 Hidradenitis suppurativa,  
 Crohn’s disease,  
 Ulcerative colitis and  
 Non-infectious uveitis 
 
The active ingredient in Humira, adalimumab, is a human monoclonal antibody. Monoclonal antibodies 
are proteins that attach to a specific target. 
 
The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the 
immune (defence) system and is present at increased levels in the inflammatory diseases listed above. By 
attaching to TNFα, Humira decreases the process of inflammation in these diseases. 
 



389 

Rheumatoid arthritis 
 
Rheumatoid arthritis is an inflammatory disease of the joints. 
 
Humira is used to treat rheumatoid arthritis in adults. If you have moderate to severe active rheumatoid 
arthritis, you may first be given other disease-modifying medicines, such as methotrexate. If you do not 
respond well enough to these medicines, you will be given Humira to treat your rheumatoid arthritis.   
 
Humira can also be used to treat severe, active and progressive rheumatoid arthritis without previous 
methotrexate treatment. 
 
Humira has been shown to slow down the damage to the cartilage and bone of the joints caused by the 
disease and to improve physical function.  
Usually, Humira is used with methotrexate. If your doctor determines that methotrexate is inappropriate, 
Humira can be given alone.  
 
Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis 
 
Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis are inflammatory diseases. 
 
Humira is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged 2 to 17 
years and enthesitis-related arthritis in children and adolescents aged 6 to 17 years. You may first be given 
other disease-modifying medicines, such as methotrexate. If you do not respond well enough to these 
medicines, you will be given Humira to treat your polyarticular juvenile idiopathic arthritis or enthesitis-
related arthritis. 
 
Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing 
spondylitis 
 
Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing 
spondylitis, are inflammatory diseases of the spine. 
 
Humira is used to treat ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of 
ankylosing spondylitis in adults. If you have ankylosing spondylitis or axial spondyloarthritis without 
radiographic evidence of ankylosing spondylitis, you will first be given other medicines. If you do not 
respond well enough to these medicines, you will be given Humira to reduce the signs and symptoms of 
your disease. 
 
Psoriatic arthritis 
 
Psoriatic arthritis is an inflammation of the joints associated with psoriasis. 
 
Humira is used to treat psoriatic arthritis in adults. Humira has been shown to slow down the damage to 
the cartilage and bone of the joints caused by the disease and to improve physical function. 
 
Plaque psoriasis in adults and children  
 
Plaque psoriasis is a skin condition that causes red, flaky, crusty patches of skin covered with silvery 
scales. Plaque psoriasis can also affect the nails, causing them to crumble, become thickened and lift away 
from the nail bed which can be painful. Psoriasis is believed to be caused by a problem with the body’s 
immune system that leads to an increased production of skin cells. 
 



390 

Humira is used to treat moderate to severe plaque psoriasis in adults. Humira is also used to treat severe 
plaque psoriasis in children and adolescents aged 4 to 17 years for whom topical therapy and 
phototherapies have either not worked very well or are not suitable. 
 
Hidradenitis suppurativa in adults and adolescents 
 
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic and often painful inflammatory skin 
disease. Symptoms may include tender nodules (lumps) and abscesses (boils) that may leak pus. It most 
commonly affects specific areas of the skin, such as under the breasts, the armpits, inner thighs, groin and 
buttocks. Scarring may also occur in affected areas. 
 
Humira is used to treat hidradenitis suppurativa in adults and adolescents from 12 years of age.  Humira 
can reduce the number of nodules and abscesses you have and the pain that is often associated with the 
disease. You may first be given other medicines. If you do not respond well enough to these medicines, 
you will be given Humira. 
 
Crohn’s disease in adults and children 
 
Crohn’s disease is an inflammatory disease of the digestive tract. 
 
Humira is used to treat Crohn’s disease in adults and children aged 6 to 17 years. If you have Crohn’s 
disease you will first be given other medicines. If you do not respond well enough to these medicines, you 
will be given Humira to reduce the signs and symptoms of your Crohn’s disease. 
 
Ulcerative colitis in adults and children 
 
Ulcerative colitis is an inflammatory disease of the large intestine. 
 
Humira is used to treat moderate to severe ulcerative colitis in adults and children aged 6 to 17 years. If 
you have ulcerative colitis you may first be given other medicines. If you do not respond well enough to 
these medicines, you will be given Humira to reduce the signs and symptoms of your disease. 
 
Non-infectious uveitis in adults and children 
 
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. 
 
Humira is used to treat  

 Adults with non-infectious uveitis with inflammation affecting the back of the eye  
 Children from 2 years of age with chronic non-infectious uveitis with inflammation affecting the 

front of the eye 
 
This inflammation may lead to a decrease of vision and/or the presence of floaters in the eye (black dots or 
wispy lines that move across the field of vision). Humira works by reducing this inflammation. 
 
 
2. What you need to know before you use Humira 
 
Do not use Humira 
 

 If you are allergic to adalimumab or any of the other ingredients of this medicine (listed in section 
6).  

 



391 

 If you have a severe infection, including active tuberculosis (see “Warnings and precautions”). It 
is important that you tell your doctor if you have symptoms of infections, e.g. fever, wounds, 
feeling tired, dental problems. 

 
 If you have moderate or severe heart failure. It is important to tell your doctor if you have had or 

have a serious heart condition (see “Warnings and precautions”). 
 
Warnings and precautions 
 
Talk to your doctor or pharmacist before using Humira 
 

 If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, 
swelling or rash do not inject more Humira and contact your doctor immediately since, in rare 
cases, these reactions can be life threatening. 
 

 If you have an infection, including long-term or localized infection (for example, leg ulcer) 
consult your doctor before starting Humira. If you are unsure, contact your doctor.  
 

 You might get infections more easily while you are receiving Humira treatment. This risk may 
increase if your lung function is impaired. These infections may be serious and include 
tuberculosis, infections caused by viruses, fungi, parasites or bacteria, or other opportunistic 
infections and sepsis that may, in rare cases, be life-threatening. It is important to tell your doctor 
if you get symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may 
recommend temporary discontinuation of Humira. 

 
 As cases of tuberculosis have been reported in patients treated with Humira, your doctor will 

check you for signs and symptoms of tuberculosis before starting Humira. This will include a 
thorough medical evaluation including your medical history and appropriate screening tests (for 
example chest X-ray and a tuberculin test). The conduct and results of these tests should be 
recorded on your Patient Reminder Card. It is very important that you tell your doctor if you 
have ever had tuberculosis, or if you have been in close contact with someone who has had 
tuberculosis. Tuberculosis can develop during therapy even if you have received preventative 
treatment for tuberculosis. If symptoms of tuberculosis (persistent cough, weight loss, listlessness, 
mild fever), or any other infection appear during or after therapy tell your doctor immediately. 

 
 Advise your doctor if you reside or travel in regions where fungal infections such as 

histoplasmosis, coccidioidomycosis or blastomycosis are endemic. 
 

 Advise your doctor if you have a history of recurrent infections or other conditions that increase 
the risk of infections. 
 

 Advise your doctor if you are a carrier of the hepatitis B virus (HBV), if you have active HBV or 
if you think you might be at risk of contracting HBV. Your doctor should test you for HBV. 
Humira can cause reactivation of HBV in people who carry this virus. In some rare cases, 
especially if you are taking other medicines that suppress the immune system, reactivation of 
HBV can be life-threatening.   

 
 If you are over 65 years you may be more susceptible to infections while taking Humira. You and 

your doctor should pay special attention to signs of infection while you are being treated with 
Humira. It is important to tell your doctor if you get symptoms of infections, such as fever, 
wounds, feeling tired or dental problems. 
 



392 

 If you are about to undergo surgery or dental procedures, please inform your doctor that you are 
taking Humira. Your doctor may recommend temporary discontinuation of Humira.  
 

 If you have or develop demyelinating disease such as multiple sclerosis, your doctor will decide if 
you should receive or continue to receive Humira. Tell your doctor immediately if you experience 
symptoms like changes in your vision, weakness in your arms or legs or numbness or tingling in 
any part of your body. 
 

 Certain vaccines may cause infections and should not be given while receiving Humira. Please 
check with your doctor before you receive any vaccines. It is recommended that children, if 
possible, be brought up to date with all immunisations in agreement with current immunisation 
guidelines prior to initiating Humira therapy. If you received Humira while you were pregnant, 
your baby may be at higher risk for getting such an infection for up to approximately five months 
after the last dose you received during pregnancy. It is important that you tell your baby's doctors 
and other health care professionals about your Humira use during your pregnancy so they can 
decide when your baby should receive any vaccine. 
 

 If you have mild heart failure and you are being treated with Humira, your heart failure status 
must be closely monitored by your doctor. It is important to tell your doctor if you have had or 
have a serious heart condition. If you develop new or worsening symptoms of heart failure (e.g. 
shortness of breath, or swelling of your feet), you must contact your doctor immediately. Your 
doctor will decide if you should receive Humira. 
 

 In some patients the body may fail to produce enough of the blood cells that help your body fight 
infections or help you to stop bleeding. If you develop a fever that does not go away, bruise or 
bleed very easily or look very pale, call your doctor right away. Your doctor may decide to stop 
treatment. 
 

 There have been very rare cases of certain kinds of cancer in children and adult patients taking 
Humira or other TNF blockers. People with more serious rheumatoid arthritis that have had the 
disease for a long time may have a higher than average risk of getting lymphoma (a cancer that 
affects the lymph system) and leukemia (a cancer that affects the blood and bone marrow). If you 
take Humira the risk of getting lymphoma, leukemia, or other cancers may increase. On rare 
occasions, a specific and severe type of lymphoma has been observed in patients taking Humira. 
Some of those patients were also treated with azathioprine or 6- mercaptopurine. Tell your doctor 
if you are taking azathioprine or 6-mercaptopurine with Humira. In addition, cases of non-
melanoma skin cancer have been observed in patients taking Humira. If new skin lesions appear 
during or after therapy or if existing lesions change appearance, tell your doctor. 
 

 There have been cases of cancers, other than lymphoma in patients with a specific type of lung 
disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another TNF blocker. 
If you have COPD, or are a heavy smoker, you should discuss with your doctor whether treatment 
with a TNF blocker is appropriate for you. 
 

 On rare occasions, treatment with Humira could result in lupus-like syndrome. Contact your 
doctor if symptoms such as persistent unexplained rash, fever, joint pain or tiredness occur. 

 
Children and adolescents 
 

 Vaccinations: if possible, children should be up to date with all vaccinations before using Humira. 
 Do not give Humira to children with polyarticular juvenile idiopathic arthritis below the age of 2 

years. 



393 

 
Other medicines and Humira 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 
 
Humira can be taken together with methotrexate or certain disease-modifying anti-rheumatic agents 
(sulfasalazine, hydroxychloroquine, leflunomide and injectable gold preparations), steroids or pain 
medications including non-steroidal anti-inflammatory drugs (NSAIDs). 
 
You should not take Humira with medicines containing the active substances anakinra or abatacept due to 
increased risk of serious infection. If you have questions, please ask your doctor. 
 
Pregnancy and breast-feeding 
 

 You should consider the use of adequate contraception to prevent pregnancy and continue its use 
for at least 5 months after the last Humira treatment. 

 If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for 
advice about taking this medicine. 

 Humira should only be used during a pregnancy if needed. 
 According to a pregnancy study, there was no higher risk of birth defects when the mother had 

received Humira during pregnancy compared with mothers with the same disease who did not 
receive Humira. 

 Humira can be used during breast-feeding. 
 If you receive Humira during your pregnancy, your baby may have a higher risk for getting an 

infection. 
 It is important that you tell your baby’s doctors and other health care professionals about your 

Humira use during your pregnancy before the baby receives any vaccine.  For more information 
on vaccines see the “Warnings and precautions” section). 

 
Driving and using machines 
 
Humira may have a minor influence on your ability to drive, cycle or use machines. Room spinning 
sensation and vision disturbances may occur after taking Humira. 
 
Humira contains sodium 
 
This medicinal product contains less than 1 mmol of sodium (23 mg) per 0.8 ml dose, i.e. essentially 
‘sodium-free’. 
 
 
3. How to use Humira 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are not sure. Your doctor may prescribe another strength of Humira if you need a 
different dose. 
 
Adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or axial spondyloarthritis 
without radiographic evidence of ankylosing spondylitis 
 
Humira is injected under the skin (subcutaneous use). The usual dose for adults with rheumatoid arthritis, 
ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of ankylosing spondylitis 
and for patients with psoriatic arthritis is 40 mg adalimumab given every other week as a single dose.   
 



394 

In rheumatoid arthritis, methotrexate is continued while using Humira. If your doctor determines that 
methotrexate is inappropriate, Humira can be given alone.  
 
If you have rheumatoid arthritis and you do not receive methotrexate with your Humira therapy, your 
doctor may decide to give 40 mg adalimumab every week or 80 mg every other week. 
 
Children, adolescents and adults with polyarticular juvenile idiopathic arthritis 
 
Children and adolescents from 2 years of age weighing 10 kg to less than 30 kg 
 
The recommended dose of Humira is 20 mg every other week. 
 
Children, adolescents and adults from 2 years of age weighing 30 kg or more 
 
The recommended dose of Humira is 40 mg every other week. 
 
Children, adolescents and adults with enthesitis-related arthritis 
 
Children and adolescents from 6 years of age weighing 15 kg to less than 30 kg 
 
The recommended dose of Humira is 20 mg every other week. 
 
Children, adolescents and adults from 6years of age weighing 30 kg or more 
 
The recommended dose of Humira is 40 mg every other week. 
 
Adults with psoriasis 
 
The usual dose for adults with psoriasis is an initial dose of 80 mg (as two 40 mg injections in one day), 
followed by 40 mg given every other week starting one week after the initial dose. You should continue to 
inject Humira for as long as your doctor has told you. Depending on your response, your doctor may 
increase the dosage to 40 mg every week or 80 mg every other week. 
 
Children and adolescents with plaque psoriasis 
 
Children and adolescents from 4 to 17 years of age weighing 15 kg to less than 30 kg 
 
The recommended dose of Humira is an initial dose of 20 mg, followed by 20 mg one week later. 
Thereafter, the usual dose is 20 mg every other week. 
 
Children and adolescents from 4 to 17 years of age weighing 30 kg or more 
 
The recommended dose of Humira is an initial dose of 40 mg, followed by 40 mg one week later. 
Thereafter, the usual dose is 40 mg every other week. 
 
Adults with hidradenitis suppurativa 
 
The usual dose regimen for hidradenitis suppurativa is an initial dose of 160 mg (as four 40 mg injections 
in one day or two 40 mg injections per day for two consecutive days), followed by an 80 mg dose (as two 
40 mg injections in one day) two weeks later. After two further weeks, continue with a dosage of 40 mg 
every week or 80 mg every other week, as prescribed by your doctor. It is recommended that you use an 
antiseptic wash daily on the affected areas. 
 



395 

Adolescents with hidradenitis suppurativa from 12 to 17 years of age weighing 30 kg or more 
 
The recommended dose of Humira is an initial dose of 80 mg (as two 40 mg injections in one day), 
followed by 40 mg every other week starting one week later. If you have an inadequate response to 
Humira 40 mg every other week, your doctor may increase the dosage to 40 mg every week or 80 mg 
every other week. 
 
It is recommended that you use an antiseptic wash daily on the affected areas. 
 
Adults with Crohn’s disease 
 
The usual dose regimen for Crohn’s disease is 80 mg (as two 40 mg injections in one day) initially 
followed by 40 mg every other week two weeks later. If a faster response is required your doctor may 
prescribe an initial dose of 160 mg (as four 40 mg injections in one day or two 40mg injections per day for 
two consecutive days), followed by 80 mg (as two 40 mg injections in one day) two weeks later and 
thereafter as 40 mg every other week. Depending on your response, your doctor may increase the dosage 
to 40 mg every week or 80 mg every other week. 
 
Children and adolescents with Crohn's disease 
 
Children and adolescents from 6 to 17 years of age weighing less than 40 kg   
 
The usual dose regimen is 40 mg initially followed by 20 mg two weeks later. If a faster response is 
required, your doctor may prescribe an initial dose of 80 mg (as two 40 mg injections in one day) 
followed by 40 mg two weeks later. 
 
Thereafter, the usual dose is 20 mg every other week. Depending on your response, your doctor may 
increase the dose frequency to 20 mg every week.   
 
Children and adolescents from 6 to 17 years of age weighing 40 kg or more  
 
The usual dose regimen is 80 mg (as two 40 mg injections in one day) initially followed by 40 mg two 
weeks later.  If a faster response is required, your doctor may prescribe an initial dose of 160 mg (as four 
40 mg injections in one day or as two 40 mg injections per day for two consecutive days) followed by 
80 mg (as two 40 mg injections in one day) two weeks later. 
 
Thereafter, the usual dose is 40 mg every other week.  Depending on your response, your doctor may 
increase the dosage to 40 mg every week or 80 mg every other week. 
 
Adults with ulcerative colitis 
 
The usual Humira dose for adults with ulcerative colitis is 160 mg (as four 40 mg injections in one day or 
two 40 mg injections per day for two consecutive days) at Week 0 and 80 mg (as two 40 mg injections in 
one day) at Week 2 and thereafter 40 mg every other week. Depending on your response, your doctor may 
increase the dosage to 40 mg every week or 80 mg every other week.     
 
Children and adolescents with ulcerative colitis 
 
Children and adolescents from 6 years of age weighing less than 40 kg 
 
The usual Humira dose is 80 mg (as two 40 mg injections in one day) initially followed by 40 mg (as one 
40 mg injection) two weeks later. Thereafter, the usual dose is 40 mg every other week.  
 



396 

Patients who turn 18 years of age while on 40 mg every other week, should continue their prescribed dose. 
 
Children and adolescents from 6 years of age weighing 40 kg or more 
 
The usual Humira dose is 160 mg (as four 40 mg injections in one day or two 40 mg injections per day for 
two consecutive days) initially, followed by 80 mg (as two 40 mg injections in one day) two weeks later. 
Thereafter the usual dose is 80 mg every other week.  
 
Patients who turn 18 years of age while on 80 mg every other week, should continue their prescribed dose. 
 
Adults with non-infectious uveitis 
 
The usual dose for adults with non-infectious uveitis is an initial dose of 80 mg (as two injections in one 
day), followed by 40 mg given every other week starting one week after the initial dose. You should 
continue to inject Humira for as long as your doctor has told you. 
 
In non-infectious uveitis, corticosteroids or other medicines that influence the immune system may be 
continued while using Humira. Humira can also be given alone. 
 
Children and adolescents with chronic non-infectious uveitis from 2 years of age 
 
Children and adolescents from 2 years of age weighing less than 30 kg 
 
The usual dose of Humira is 20 mg every other week with methotrexate. 
 
Your doctor may also prescribe an initial dose of 40 mg which may be administered one week prior to the 
start of the usual dose. 
 
Children and adolescents from 2 years of age weighing 30 kg or more 
 
The usual dose of Humira is 40 mg every other week with methotrexate. 
 
Your doctor may also prescribe an initial dose of 80 mg which may be administered one week prior to the 
start of the usual dose. 
 
Method and route of administration 
 
Humira is administered by injection under the skin (by subcutaneous injection). 
 
Injecting Humira yourself 
 
The following instructions explain how to give yourself an injection of Humira using the pre-filled pen. 
Please read the instructions carefully and follow them step by step. You will be instructed by your doctor 
or his/her assistant on the technique of self-injection. Do not attempt to self-inject until you are sure that 
you understand how to prepare and give the injection. After proper training, the injection can be self-
administered or given by another person, for example a family member or friend. 
 
What should I do before I give myself a subcutaneous injection of Humira? 
 



397 

1. Wash your hands thoroughly.  
2.  Take one dose tray containing a pre-filled pen of Humira from the refrigerator.  
3.  Do not shake or drop the pre-filled pen. 
4.  Set up the following items on a clean surface. 
 

One pre-filled pen of Humira  
One alcohol pad 
 

 
 
Pad 
 
 
Window 

 
5.  Check the expiry date on the pre-filled pen label (EXP:) Do not use the product if the date has 

passed the month and year shown. 
 
6.  Hold the pre-filled pen with the grey cap (labelled ‘1’) pointing up. Check the appearance of the 

Humira solution through the window on the sides of the pre-filled pen. It must be clear and 
colourless. If it is cloudy or discoloured or has flakes or particles in it, you must not use it. Do not 
use a pre-filled pen that is frozen or if it has been left in direct sunlight. Only remove both the grey 
cap and the plum cap immediately before injection 

 
 
 
 
Window 
 
Clear Liquid in Syringe 

 
Where should I give my injection?   
 
1.  Choose a site on the top of your thigh or stomach (except the area around the navel). 



398 

 

 
 
2.  Change the place that you inject each time so that you do not become sore in one area. Each new 

injection should be given at least 3 cm from the last injection site.  
 
3.  Do not inject in an area where the skin is reddened, bruised, or hard. This may mean there is an 

infection.   
 

How do I give my injection? 
 
1.  Wipe your skin by using the enclosed alcohol pad, using a circular motion. Do not touch the area 

again before injecting.     
 
2. Only remove both the grey cap and the plum cap immediately before injection. Hold the grey body 

of the pre-filled pen with one hand. Place hand on the middle of the pen so that neither the grey cap 
(1) nor the plum cap (2) is covered. Hold the pre-filled pen with the grey cap (1) pointing up. With 
your other hand, pull the grey cap (1) straight off, check that the small black needle cover of the 
syringe has been removed with the cap, then discard cap. If a few small drops of liquid come out of 
the needle, that is okay. The white needle sleeve will now be exposed. Do not try to touch the needle 
housed in the barrel. DO NOT RECAP as you may damage the needle inside.  

 

 
 
3.  Pull the plum safety cap (labelled ‘2’) straight off to expose the plum coloured activation button. 

The pre-filled pen is now ready to use. Do not press the plum activation button until properly 
positioned as this will result in discharge of medication. DO NOT RECAP as this could cause the 
unit to discharge. 

 



399 

Giving the injection 
 
1.  With your free hand, gently grasp a sizable area of the cleaned skin at the injection site and hold 

firmly (see below).   
2.   Place the white end of the pre-filled pen at a right angle (90 degrees) to the skin, so that you can see 

the window. The presence of one or more bubbles in the window is normal. 
3.  Holding the barrel of the pre-filled pen, press down slightly onto the injection site (holding in place 

without moving).  
4.  With your index finger or your thumb, press the plum coloured button on top once you are ready to 

begin the injection (see below). You will then hear a loud ‘click’ as the needle is released and you 
will feel a small prick as the needle advances.  

5.  Keep pressing and continue to hold the pre-filled pen with steady pressure in place for about 10 
seconds to ensure a complete injection. Do not remove the pre-filled pen while the injection is 
being given.  

 

 
 
6.  You will see a yellow indicator move into the window during the injection. The injection is 

complete when the yellow indicator stops moving. The yellow indicator is part of the plunger of the 
pre-filled pen. If the yellow indicator is not shown in the window, the plunger has not advanced 
adequately and the injection is not complete.   

 
7.  Lift the pre-filled pen straight up from the injection site. The white needle sleeve will move down 

over the needle and lock into place over the needle tip. Do not try to touch the needle. The white 
needle sleeve is there to protect you from touching the needle.    

 

 

 
White Needle 
Sleeve 

 

 
 
 
Window 
 
Yellow Indicator 
Visible 
 

 
8.  You may notice a spot of blood at the injection site. You can press a cotton ball or a piece of gauze 

over the injection site for 10 seconds. Do not rub the injection site. Use a plaster if you want to. 
 
Throwing away supplies 
 
Only use each pre-filled pen for one injection. Do not put either of the caps back on the pre-filled pen. 



400 

After injecting Humira, immediately throw away the used pre-filled pen in a special container as 
instructed by your doctor, nurse or pharmacist 
Keep this container out of the sight and reach of children 
 
If you use more Humira than you should 
 
If you accidentally inject Humira more frequently than told to by your doctor or pharmacist, call your 
doctor or pharmacist and tell him/her that you have taken more. Always take the outer carton of the 
medicine with you, even if it is empty.  
 
If you forget to use Humira 
 
If you forget to give yourself an injection, you should inject the next dose of Humira as soon as you 
remember. Then take your next dose as you would have on your originally scheduled day, had you not 
forgotten a dose.  
 
If you stop using Humira 
 
The decision to stop using Humira should be discussed with your doctor. Your symptoms may return upon 
discontinuation. 
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side 
effects are mild to moderate. However, some may be serious and require treatment. Side effects may occur 
at least up to 4 months after the last Humira injection. 
 
Tell your doctor immediately if you notice any of the following  
 severe rash, hives or other signs of allergic reaction;  
 swollen face, hands, feet; 
 trouble breathing, swallowing; 
 shortness of breath with exertion or upon lying down or swelling of the feet. 

 
Tell your doctor as soon as possible if you notice any of the following 
 signs of infection such as fever, feeling sick, wounds, dental problems, burning on urination; 
 feeling weak or tired; 
 coughing; 
 tingling; 
 numbness; 
 double vision; 
 arm or leg weakness; 
 a bump or open sore that doesn't heal; 
 signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, 

paleness. 
 
The symptoms described above can be signs of the below listed side effects, which have been observed 
with Humira. 
 



401 

Very common (may affect more than 1 in 10 people) 
 
 injection site reactions (including pain, swelling, redness or itching); 
 respiratory tract infections (including cold, runny nose, sinus infection, pneumonia); 
 headache; 
 abdominal pain; 
 nausea and vomiting; 
 rash; 
 musculoskeletal pain. 
 
Common (may affect up to 1 in 10 people)  
 
 serious infections (including blood poisoning and influenza); 
 intestinal infections (including gastroenteritis); 
 skin infections (including cellulitis and shingles); 
 ear infections; 
 oral infections (including tooth infections and cold sores); 
 reproductive tract infections; 
 urinary tract infection; 
 fungal infections; 
 joint infections; 
 benign tumours; 
 skin cancer; 
 allergic reactions (including seasonal allergy); 
 dehydration; 
 mood swings (including depression); 
 anxiety; 
 difficulty sleeping; 
 sensation disorders such as tingling, prickling or numbness; 
 migraine; 
 nerve root compression (including low back pain and leg pain); 
 vision disturbances;  
 eye inflammation; 
 inflammation of the eye lid and eye swelling; 
 vertigo; 
 sensation of heart beating rapidly; 
 high blood pressure; 
 flushing; 
 haematoma; 
 cough; 
 asthma; 
 shortness of breath; 
 gastrointestinal bleeding; 
 dyspepsia (indigestion, bloating, heart burn); 
 acid reflux disease; 
 sicca syndrome (including dry eyes and dry mouth); 
 itching; 
 itchy rash; 
 bruising; 
 inflammation of the skin (such as eczema); 



402 

 breaking of finger nails and toe nails; 
 increased sweating; 
 hair loss; 
 new onset or worsening of psoriasis; 
 muscle spasms; 
 blood in urine; 
 kidney problems; 
 chest pain; 
 oedema; 
 fever; 
 reduction in blood platelets which increases risk of bleeding or bruising; 
 impaired healing. 
 
Uncommon (may affect up to 1 in 100 people)  
 
 opportunistic infections (which include tuberculosis and other infections that occur when resistance 

to disease is lowered); 
 neurological infections (including viral meningitis); 
 eye infections; 
 bacterial infections; 
 diverticulitis (inflammation and infection of the large intestine); 
 cancer; 
 cancer that affects the lymph system; 
 melanoma; 
 immune disorders that could affect the lungs, skin and lymph nodes (most commonly presenting as 

sarcoidosis); 
 vasculitis (inflammation of blood vessels); 
 tremor; 
 neuropathy; 
 stroke; 
 hearing loss, buzzing; 
 sensation of heart beating irregularly such as skipped beats; 
 heart problems that can cause shortness of breath or ankle swelling; 
 heart attack; 
 a sac in the wall of a major artery, inflammation and clot of a vein, blockage of a blood vessel; 
 lung diseases causing shortness of breath (including inflammation); 
 pulmonary embolism (blockage in an artery of the lung); 
 pleural effusion (abnormal collection of fluid in the pleural space); 
 inflammation of the pancreas which causes severe pain in the abdomen and back; 
 difficulty in swallowing; 
 facial oedema; 
 gallbladder inflammation, gallbladder stones; 
 fatty liver; 
 night sweats; 
 scar; 
 abnormal muscle breakdown; 
 systemic lupus erythematosus (including inflammation of skin, heart, lung, joints and other organ 

systems); 
 sleep interruptions; 
 impotence; 



403 

 inflammations. 
 
Rare (may affect up to 1 in 1,000 people) 
 
 leukemia (cancer affecting the blood and bone marrow); 
 severe allergic reaction with shock; 
 multiple sclerosis; 
 nerve disorders (such as eye nerve inflammation and Guillain-Barré syndrome that may cause 

muscle weakness, abnormal sensations, tingling in the arms and upper body); 
 heart stops pumping; 
 pulmonary fibrosis (scarring of the lung); 
 intestinal perforation; 
 hepatitis; 
 reactivation of hepatitis B; 
 autoimmune hepatitis (inflammation of the liver caused by the body's own immune system); 
 cutaneous vasculitis (inflammation of blood vessels in the skin); 
 Stevens-Johnson syndrome (early symptoms include malaise, fever, headache and rash); 
 facial oedema associated with allergic reactions; 
 erythema multiforme (inflammatory skin rash); 
 lupus-like syndrome; 
 angioedema (localized swelling of the skin); 
 lichenoid skin reaction (itchy reddish-purple skin rash). 
 
Not known (frequency cannot be estimated from available data) 
 
 hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal); 
 Merkel cell carcinoma (a type of skin cancer); 
 Kaposi’s sarcoma, a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma 

most commonly appears as purple lesions on the skin; 
 liver failure; 
 worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle         

weakness). 
 
Some side effects observed with Humira may not have symptoms and may only be discovered through 
blood tests. These include: 
 
Very common (may affect more than 1 in 10 people) 
 
 low blood measurements for white blood cells; 
 low blood measurements for red blood cells; 
 increased lipids in the blood; 
 elevated liver enzymes. 
 
Common (may affect up to 1 in 10 people) 
 
 high blood measurements for white blood cells;   
 low blood measurements for platelets; 
 increased uric acid in the blood; 
 abnormal blood measurements for sodium; 
 low blood measurements for calcium; 
 low blood measurements for phosphate; 



404 

 high blood sugar; 
 high blood measurements for lactate dehydrogenase; 
 autoantibodies present in the blood; 
 low blood potassium. 
 
Uncommon (may affect up to 1 in 100 people) 
 
 elevated bilirubin measurement (liver blood test). 
 
Rare (may affect up to 1 in 1,000 people) 
 
 low blood measurements for white blood cells, red blood cells and platelet count. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects, you can help provide more information on the safety of this 
medicine.  
 
 
5. How to store Humira 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date stated on the label/blister/carton after EXP. 
 
Store in a refrigerator (2C – 8C). Do not freeze. 
 
Keep the pre-filled pen in the outer carton in order to protect from light. 
 
Alternative Storage: 
 
When needed (for example when you are travelling), a single Humira pre-filled pen may be stored at room 
temperature (up to 25°C) for a maximum period of 14 days – be sure to protect it from light. Once 
removed from the refrigerator for room temperature storage, the pen must be used within 14 days or 
discarded, even if it is returned to the refrigerator.   
 
You should record the date when the pen is first removed from refrigerator and the date after which it 
should be discarded. 
 
Do not throw away any medicines via wastewater or household waste. Ask your doctor or pharmacist how 
to throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Humira contains 
 
The active substance is adalimumab. 
The other ingredients are mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen phosphate 
dihydrate, disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and water 
for injections. 
 



405 

 
What the Humira pre-filled pen looks like and contents of the pack 
 
Humira 40 mg solution for injection in pre-filled pen is supplied as a sterile solution of 40 mg adalimumab 
dissolved in 0.8 ml solution. 
 
The Humira pre-filled pen is a single-use grey and plum-coloured pen which contains a glass syringe with 
Humira. There are two caps – one is grey and labelled ‘1’ and the other is plum and labelled ‘2’. There is a 
window on each side of the pen through which you can see the Humira solution inside the syringe.   
 
The Humira pre-filled pen is available in packs containing 1, 2, 4 and 6 pre-filled pens. The 1 pre-filled 
pen pack comes with 2 alcohol pads (1 spare). For the 2, 4 and 6 pre-filled pen packs, each pre-filled pen 
comes with 1 alcohol pad.   
 
Not all pack sizes may be marketed.   
 
Humira may be available as a vial, a pre-filled syringe and/or a pre-filled pen. 
 
Marketing Authorisation Holder 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
Manufacturer  
 
AbbVie Biotechnology GmbH 
Max-Planck-Ring 2 
D – 65205 Wiesbaden 
Germany 
 
and 
 
AbbVie Biotechnology GmbH 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder. 
 
België/Belgique/Belgien 
AbbVie SA 
Tél/Tel: +32 10  477811 

Lietuva 
AbbVie UAB  
Tel: +370 5 205 3023 

България 
АбВи ЕООД 
Тел.:+359 2 90 30 430 

Luxembourg/Luxemburg 
AbbVie SA 
Belgique/Belgien 
Tél/Tel: +32 10 477811

Česká republika 
AbbVie s.r.o.  
Tel: +420 233 098 111 

Magyarország 
AbbVie Kft. 
Tel.:+36 1 455 8600



406 

Danmark 
AbbVie A/S 
Tlf: +45 72 30-20-28 

Malta 
V.J.Salomone Pharma Limited  
Tel: +356 22983201

Deutschland 
AbbVie Deutschland GmbH & Co. KG 
Tel: 00800 222843 33 (gebührenfrei) 
Tel: +49 (0) 611 / 1720-0

Nederland 
AbbVie B.V. 
Tel:  +31 (0)88 322 2843 

Eesti 
AbbVie Biopharmaceuticals GmbH Eesti filiaal  
Tel: +372 623 1011 

Norge 
AbbVie AS 
Tlf: +47 67 81 80 00

Ελλάδα 
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. 
Τηλ: +30 214 4165 555 

Österreich 
AbbVie GmbH  
Tel: +43 1 20589-0 

España 
AbbVie Spain, S.L.U. 
Tel:  +34 91 384 09 10 

Polska 
AbbVie Polska Sp. z o.o. 
Tel.: +48 22 372 78 00 

France 
AbbVie 
Tél: +33 (0) 1 45 60 13 00 

Portugal 
AbbVie, Lda.  
Tel: +351 (0)21 1908400 

Hrvatska  
AbbVie d.o.o. 
Tel + 385 (0)1 5625 501

România 
AbbVie S.R.L. 
Tel: +40 21 529 30 35

Ireland 
AbbVie Limited  
Tel: +353 (0)1 4287900

Slovenija 
AbbVie Biofarmacevtska družba d.o.o. 
Tel: +386 (1)32 08 060

Ísland 
Vistor hf. 
Tel: +354 535 7000 

Slovenská republika 
AbbVie s.r.o. 
Tel: +421 2 5050 0777

Italia 
AbbVie S.r.l.  
Tel: +39 06 928921 

Suomi/Finland 
AbbVie Oy  
Puh/Tel:  +358 (0)10 2411 200 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Τηλ.: +357 22 34 74 40

Sverige 
AbbVie AB 
Tel:  +46 (0)8 684 44 600

Latvija 
AbbVie SIA  
Tel: +371 67605000 

United Kingdom 
AbbVie Ltd  
Tel: +44 (0)1628 561090

 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the 
local representative of the Marketing Authorisation Holder.  



407 

Package leaflet: Information for the patient 
 

Humira 40 mg solution for injection in pre-filled syringe 
adalimumab 

 
Read all of this leaflet carefully before you start using this medicine because it contains important 
information for you. 
 Keep this leaflet. You may need to read it again. 
 Your doctor will also give you a Patient Reminder Card, which contains important safety 

information that you need to be aware of before you begin using Humira and during treatment with 
Humira. Keep this Patient Reminder Card with you. 

 If you have any questions, ask your doctor or pharmacist. 
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even 

if their signs of illness are the same as yours. 
 If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet  
1. What Humira is and what it is used for 
2. What you need to know before you use Humira 
3. How to use Humira 
4. Possible side effects 
5 How to store Humira 
6. Contents of the pack and other information 
7. Injecting Humira 
 
 
1. What Humira is and what it is used for 
 
Humira contains the active substance adalimumab. 
 
Humira is used to treat 

 Rheumatoid arthritis 
 Polyarticular juvenile idiopathic arthritis 
 Enthesitis-related arthritis 
 Ankylosing spondylitis 
 Axial spondyloarthritis without radiographic evidence of ankylosing spondylitis 
 Psoriatic arthritis 
 Plaque psoriasis 
 Hidradenitis suppurativa 
 Crohn’s disease 
 Ulcerative colitis 
 Non-infectious uveitis 

 
The active ingredient in Humira, adalimumab, is a human monoclonal antibody. Monoclonal antibodies 
are proteins that attach to a specific target. 
 
The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the 
immune (defence) system and is present at increased levels in the inflammatory diseases listed above. By 
attaching to TNFα, Humira decreases the process of inflammation in these diseases. 
 



408 

Rheumatoid arthritis 
 
Rheumatoid arthritis is an inflammatory disease of the joints. 
 
Humira is used to treat moderate to severe rheumatoid arthritis in adults. You may first be given other 
disease-modifying medicines, such as methotrexate. If you do not respond well enough to these medicines, 
you will be given Humira. 
 
Humira can also be used to treat severe, active and progressive rheumatoid arthritis without previous 
methotrexate treatment. 
 
Humira can slow down the damage to the joints caused by the inflammatory disease and can help them 
move more freely.  
 
Your doctor will decide if Humira should be used with methotrexate or alone.  
 
Polyarticular juvenile idiopathic arthritis  
 
Polyarticular juvenile idiopathic arthritis is an inflammatory disease of the joints. 
 
Humira is used to treat polyarticular juvenile idiopathic arthritis in patients from 2 years of age. You may 
first be given other disease-modifying medicines, such as methotrexate. If you do not respond well enough 
to these medicines, you will be given Humira. 
 
Your doctor will decide if Humira should be used with methotrexate or alone. 
 
Enthesitis-related arthritis 
 
Enthesitis-related arthritis is an inflammatory disease of the joints and the places where tendons join the 
bone. 
 
Humira is used to treat enthesitis-related arthritis in patients from 6 years of age. You may first be given 
other disease-modifying medicines, such as methotrexate. If you do not respond well enough to these 
medicines, you will be given Humira. 
 
Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing 
spondylitis  
 
Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing 
spondylitis are inflammatory diseases of the spine. 
 
Humira is used to treat severe ankylosing spondylitis and axial spondyloarthritis without radiographic 
evidence of ankylosing spondylitis in adults. You may first be given other medicines. If you do not 
respond well enough to these medicines, you will be given Humira. 
 
Psoriatic arthritis 
 
Psoriatic arthritis is an inflammatory disease of the joints that is usually associated with psoriasis. 
 
Humira is used to treat psoriatic arthritis in adults. Humira can slow down the damage to the joints caused 
by the disease and can help them move more freely. You may first be given other medicines. If you do not 
respond well enough to these medicines, you will be given Humira. 
 



409 

Plaque psoriasis  
 
Plaque psoriasis is a skin condition that causes red, flaky, crusty patches of skin covered with silvery 
scales. Plaque psoriasis can also affect the nails, causing them to crumble, become thickened and lift away 
from the nail bed which can be painful. 
 
Humira is used to treat 

 moderate to severe chronic plaque psoriasis in adults and  
 severe chronic plaque psoriasis in children and adolescents aged 4 to 17 years for whom topical 

therapy and phototherapies have either not worked very well or are not suitable. 
 
Hidradenitis suppurativa  
 
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic and often painful inflammatory skin 
disease. Symptoms may include tender nodules (lumps) and abscesses (boils) that may leak pus. It most 
commonly affects specific areas of the skin, such as under the breasts, the armpits, inner thighs, groin and 
buttocks. Scarring may also occur in affected areas. 
 
Humira is used to treat  

 moderate to severe hidradenitis suppurativa in adults and 
 moderate to severe hidradenitis suppurativa in adolescents aged 12 to 17 years.  

 
Humira can reduce the number of nodules and abscesses caused by the disease and the pain that is often 
associated with the disease. You may first be given other medicines. If you do not respond well enough to 
these medicines, you will be given Humira. 
 
Crohn’s disease  
 
Crohn’s disease is an inflammatory disease of the digestive tract. 
 
Humira is used to treat 

 moderate to severe Crohn’s disease in adults and  
 moderate to severe Crohn’s disease in children and adolescents aged 6 to 17 years 
 

You may first be given other medicines. If you do not respond well enough to these medicines, you will be 
given Humira. 
 
Ulcerative colitis 
 
Ulcerative colitis is an inflammatory disease of the large intestine. 
 
Humira is used to treat  

 moderate to severe ulcerative colitis in adults and 
 moderate to severe ulcerative colitis in children and adolescents aged 6 to 17 years  

 
You may first be given other medicines. If you do not respond well enough to these medicines, you will be 
given Humira. 
 
Non-infectious uveitis 
 
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. 
 
Humira is used to treat  



410 

 adults with non-infectious uveitis with inflammation affecting the back of the eye 
 children with chronic non-infectious uveitis from 2 years of age with inflammation affecting the 

front of the eye  
 
This inflammation may lead to a decrease of vision and/or the presence of floaters in the eye (black dots or 
wispy lines that move across the field of vision). Humira works by reducing this inflammation. 
 
You may first be given other medicines. If you do not respond well enough to these medicines, you will be 
given Humira. 
 
 
2. What you need to know before you use Humira 
 
Do not use Humira: 
 

 If you are allergic to adalimumab or any of the other ingredients of this medicine (listed in section 
6).  

 
 If you have active tuberculosis or other severe infections (see “Warnings and precautions”). It is 

important that you tell your doctor if you have symptoms of infections, for example, fever, 
wounds, feeling tired, dental problems. 
 

 If you have moderate or severe heart failure. It is important to tell your doctor if you have had or 
have a serious heart condition (see “Warnings and precautions”). 

 
Warnings and precautions 
 
Talk to your doctor or pharmacist before using Humira. 
 
Allergic reactions 
 

 If you get allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling 
or rash do not inject more Humira and contact your doctor immediately since, in rare cases, these 
reactions can be life threatening. 
 

Infections 
 

 If you have an infection, including long-term infection or an infection in one part of the body (for 
example, leg ulcer) consult your doctor before starting Humira. If you are unsure, contact your 
doctor.  

 
 You might get infections more easily while you are receiving Humira treatment. This risk may 

increase if you have problems with your lungs. These infections may be serious and include:  
 tuberculosis 
 infections caused by viruses, fungi, parasites or bacteria 
 severe infection in the blood (sepsis) 

 
In rare cases, these infections can be life-threatening. It is important to tell your doctor if you get 
symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may tell you to 
stop using Humira for some time. 
 



411 

 Tell your doctor if you live or travel in regions where fungal infections (for example, 
histoplasmosis, coccidioidomycosis or blastomycosis) are very common. 

 
 Tell your doctor if you have had infections which keep coming back or other conditions that 

increase the risk of infections. 
 

 If you are over 65 years you may be more likely to get infections while taking Humira. You and 
your doctor should pay special attention to signs of infection while you are being treated with 
Humira. It is important to tell your doctor if you get symptoms of infections, such as fever, 
wounds, feeling tired or dental problems. 

 
Tuberculosis 
 

 It is very important that you tell your doctor if you have ever had tuberculosis, or if you have been 
in close contact with someone who has had tuberculosis. If you have active tuberculosis, do not 
use Humira. 

 
 As cases of tuberculosis have been reported in patients treated with Humira, your doctor 

will check you for signs and symptoms of tuberculosis before starting Humira. This will 
include a thorough medical evaluation including your medical history and appropriate 
screening tests (for example, chest X-ray and a tuberculin test). The conduct and results of 
these tests should be recorded on your Patient Reminder Card.  

 Tuberculosis can develop during therapy even if you have received treatment for the 
prevention of tuberculosis.  

 If symptoms of tuberculosis (for example, cough that does not go away, weight loss, lack 
of energy, mild fever), or any other infection appear during or after therapy tell your 
doctor immediately.  

 
Hepatitis B 
 

 Tell your doctor if you are a carrier of the hepatitis B virus (HBV), if you have active HBV or if 
you think you might be at risk of getting HBV.  

 Your doctor should test you for HBV. In people who carry HBV, Humira can cause the 
virus to become active again. 

 In some rare cases, especially if you are taking other medicines that suppress the immune 
system, reactivation of HBV can be life-threatening.   

 
Surgery or dental procedure 
 

 If you are about to have surgery or dental procedures, please inform your doctor that you are 
taking Humira. Your doctor may recommend temporary discontinuation of Humira.  
 

Demyelinating disease 
 

 If you have or develop a demyelinating disease (a disease that affects the insulating layer around 
the nerves, such as multiple sclerosis), your doctor will decide if you should receive or continue to 
receive Humira. Tell your doctor immediately if you experience symptoms like changes in your 
vision, weakness in your arms or legs or numbness or tingling in any part of your body. 
 

Vaccinations 
 

 Certain vaccines may cause infections and should not be given while receiving Humira.  



412 

 
 Check with your doctor before you receive any vaccines.  
 It is recommended that children, if possible, be given all the scheduled vaccinations for 

their age before they start treatment with Humira. 
 If you received Humira while you were pregnant, your baby may be at higher risk for 

getting such an infection for up to approximately five months after the last Humira dose 
you received during pregnancy. It is important that you tell your baby's doctors and other 
health care professionals about your Humira use during your pregnancy so they can 
decide when your baby should receive any vaccine. 

 
Heart failure 
 

 If you have mild heart failure and are being treated with Humira, your heart failure status must be 
closely monitored by your doctor. It is important to tell your doctor if you have had or have a 
serious heart condition. If you develop new or worsening symptoms of heart failure (e.g. shortness 
of breath, or swelling of your feet), you must contact your doctor immediately. Your doctor will 
decide if you should receive Humira. 

 
Fever, bruising, bleeding or looking pale 
 

 In some patients the body may fail to produce enough of the blood cells that fight off infections or 
help you to stop bleeding. Your doctor may decide to stop treatment. If you develop a fever that 
does not go away, develop light bruises or bleed very easily or look very pale, call your doctor 
right away.  

 
Cancer 
 

 There have been very rare cases of certain kinds of cancer in children and adult patients taking 
Humira or other TNF blockers.   

 
 People with more serious rheumatoid arthritis that have had the disease for a long time 

may have a higher than average risk of getting lymphoma (a cancer that affects the lymph 
system) and leukaemia (a cancer that affects the blood and bone marrow).  

 If you take Humira the risk of getting lymphoma, leukaemia, or other cancers may 
increase. On rare occasions, an uncommon and severe type of lymphoma, has been seen in 
patients taking Humira. Some of those patients were also treated with azathioprine or 6-
mercaptopurine.  

 Tell your doctor if you are taking azathioprine or 6-mercaptopurine with Humira.  
 Cases of non-melanoma skin cancer have been observed in patients taking Humira. 
 If new skin lesions appear during or after therapy or if existing lesions change appearance, 

tell your doctor. 
 

 There have been cases of cancers, other than lymphoma in patients with a specific type of lung 
disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another TNF blocker. 
If you have COPD, or are a heavy smoker, you should discuss with your doctor whether treatment 
with a TNF blocker is appropriate for you. 
 

Autoimmune disease 
 

 On rare occasions, treatment with Humira could result in lupus-like syndrome. Contact your 
doctor if symptoms such as persistent unexplained rash, fever, joint pain or tiredness occur. 

 



413 

Children and adolescents 
 

 Vaccinations: if possible, children should be up to date with all vaccinations before using Humira. 
 

Other medicines and Humira 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 
 
You should not take Humira with medicines containing the following active substances due to increased 
risk of serious infection: 

 anakinra 
 abatacept. 

 
Humira can be taken together with: 

 methotrexate 
 certain disease-modifying anti-rheumatic agents (for example, sulfasalazine, hydroxychloroquine, 

leflunomide and injectable gold preparations) 
 steroids or pain medications including non-steroidal anti-inflammatory drugs (NSAIDs). 

 
If you have questions, please ask your doctor. 
 
Pregnancy and breast-feeding 
 

 You should consider the use of adequate contraception to prevent pregnancy and continue its use 
for at least 5 months after the last Humira treatment. 

 If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for 
advice about taking this medicine. 

 Humira should only be used during a pregnancy if needed. 
 According to a pregnancy study, there was no higher risk of birth defects when the mother had 

received Humira during pregnancy compared with mothers with the same disease who did not 
receive Humira. 

 Humira can be used during breast-feeding. 
 If you receive Humira during your pregnancy, your baby may have a higher risk for getting an 

infection. 
 It is important that you tell your baby’s doctors and other health care professionals about your 

Humira use during your pregnancy before the baby receives any vaccine. For more information on 
vaccines see the “Warnings and precautions” section. 

 
Driving and using machines 
 
Humira may have a small effect on your ability to drive, cycle or use machines. Room spinning sensation 
and vision disturbances may occur after taking Humira. 
 
 
3. How to use Humira 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are not sure.  
 
The recommended doses for Humira in each of the approved uses are shown in the following table. Your 
doctor may prescribe another strength of Humira if you need a different dose. 
 



414 

Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or axial spondyloarthritis 
without radiographic evidence of ankylosing spondylitis 
Age or body weight How much and how often to 

take?
Notes 

Adults  40 mg every other week In rheumatoid arthritis, 
methotrexate is continued while 
using Humira. If your doctor 
decides that methotrexate is 
inappropriate, Humira can be 
given alone. 
 
If you have rheumatoid arthritis 
and you do not receive 
methotrexate with your Humira 
therapy, your doctor may decide 
to give Humira 40 mg every 
week or 80 mg every other 
week. 

 
Polyarticular juvenile idiopathic arthritis
Age or body weight How much and how often to 

take?
Notes 

Children, adolescents and adults 
from 2 years of age weighing 30 
kg or more 

40 mg every other week Not applicable 

Children and adolescents from 2 
years of age weighing 10 kg to 
less than 30 kg 

20 mg every other week  Not applicable 

 
Enthesitis-related arthritis 
Age or body weight How much and how often to 

take?
Notes 

Children, adolescents and adults 
from 6 years of age weighing 30 
kg or more 

40 mg every other week  Not applicable 

Children and adolescents from 6 
years of age weighing 15 kg to 
less than 30 kg 

20 mg every other week Not applicable 

 
Plaque psoriasis 
Age or body weight How much and how often to 

take?
Notes 

Adults  
 

First dose of 80 mg (two 40 mg 
injections in one day), followed 
by 40 mg every other week 
starting one week after the first 
dose. 

If you have an inadequate 
response, your doctor may 
increase the dosage to 40 mg 
every week or 80 mg every 
other week. 

Children and adolescents from 4 
to 17 years of age weighing 30 
kg or more 

First dose of 40 mg, followed by 
40 mg one week later. 
 

Not applicable 



415 

Thereafter, the usual dose is 40 
mg every other week.

Children and adolescents from 4 
to 17 years of age weighing 15 
kg to less than 30 kg 

First dose of 20 mg, followed by 
20 mg one week later. 
 
Thereafter, the usual dose is 20 
mg every other week.

Not applicable 

 
Hidradenitis suppurativa 
Age or body weight How much and how often to 

take?
Notes 

Adults  First dose of 160 mg (four 40 
mg injections in one day or two 
40 mg injections per day for two 
consecutive days), followed by 
an 80 mg dose (two 40 mg 
injections in one day) two 
weeks later. After two further 
weeks, continue with a dose of 
40 mg every week or 80 mg 
every other week, as prescribed 
by your doctor.  

It is recommended that you use 
an antiseptic wash daily on the 
affected areas. 
 

Adolescents from 12 to 17 years 
of age weighing 30 kg or more 

First dose of 80 mg (two 40 mg 
injections in one day), followed 
by 40 mg every other week 
starting one week later.   

If you have an inadequate 
response to Humira 40 mg every 
other week, your doctor may 
increase the dosage to 40 mg 
every week or 80 mg every 
other week. 
It is recommended that you use 
an antiseptic wash daily on the 
affected areas. 

 
Crohn’s disease 
Age or body weight How much and how often to 

take?
Notes 

Children, adolescents and adults 
from 6 years of age weighing 40 
kg or more 

First dose of 80 mg (two 40 mg 
injections in one day), followed 
by 40 mg two weeks later. 
 
If a faster response is required, 
the doctor may prescribe a first 
dose of 160 mg (four 40 mg 
injections in one day or two 40 
mg injections per day for two 
consecutive days), followed by 
80 mg (two 40 mg injections in 
one day) two weeks later. 
 
Thereafter, the usual dose is 40 
mg every other week.

Your doctor may increase the 
dosage to 40 mg every week or 
80 mg every other week. 
 



416 

Children and adolescents from 6 
to 17 years of age weighing less 
than 40 kg 

First dose of 40 mg, followed by 
20 mg two weeks later.  
 
If a faster response is required, 
the doctor may prescribe a first 
dose of 80 mg (two 40 mg 
injections in one day), followed 
by 40 mg two weeks later. 
 
Thereafter, the usual dose is 20 
mg every other week.

Your doctor may increase the 
dose frequency to 20 mg every 
week. 
 

 
Ulcerative colitis 
Age or body weight How much and how often to 

take?
Notes 

Adults First dose of 160 mg (four 40 
mg injections in one day or two 
40 mg injections per day for two 
consecutive days), followed by 
80 mg (two 40 mg injections in 
one day) two weeks later. 
 
Thereafter, the usual dose is 40 
mg every other week.

Your doctor may increase the 
dosage to 40 mg every week or 
80 mg every other week. 

Children and adolescents from 6 
years of age weighing less than 
40 kg 

First dose of 80 mg (two 40 mg 
injections in one day), followed 
by 40 mg (one 40 mg injection) 
two weeks later. 
 
Thereafter, the usual dose is 40 
mg every other week.

You should continue taking 
Humira at your usual dose, even 
after turning 18 years of age. 

Children and adolescents from 6 
years of age weighing 40 kg or 
more 

First dose of 160 mg (four 40 
mg injections in one day or two 
40 mg injections per day for two 
consecutive days), followed by 
80 mg (two 40 mg injections in 
one day) two weeks later. 
 
Thereafter, the usual dose is 80 
mg every other week.

You should continue taking 
Humira at your usual dose, even 
after turning 18 years of age. 

 



417 

Non-infectious uveitis 
Age or body weight How much and how often to 

take?
Notes 

Adults First dose of 80 mg (two 40 mg 
injections in one day), followed 
by 40 mg every other week 
starting one week after the first 
dose.

Corticosteroids or other 
medicines that influence the 
immune system may be 
continued while using Humira. 
Humira can also be given alone.

Children and adolescents from 
2 years of age weighing less 
than 30 kg 
 

20 mg every other week Your doctor may prescribe an 
initial dose of 40 mg to be 
administered one week prior to 
the start of the usual dose of 
20 mg every other week. 
Humira is recommended for use 
in combination with 
methotrexate. 

Children and adolescents from 
2 years of age weighing at least 
30 kg 
 

40 mg every other week  Your doctor may prescribe an 
initial dose of 80 mg to be 
administered one week prior to 
the start of the usual dose of 
40 mg every other week. 
Humira is recommended for use 
in combination with 
methotrexate. 

 
Method and route of administration 
 
Humira is administered by injection under the skin (by subcutaneous injection). 
 
Detailed instructions on how to inject Humira are provided in section 7 ‘Injecting Humira’. 
 
If you use more Humira than you should 
 
If you accidentally inject Humira more frequently than told to by your doctor or pharmacist, call your 
doctor or pharmacist and tell them that you have taken more. Always take the outer carton of the medicine 
with you, even if it is empty.  
 
If you forget to use Humira 
 
If you forget to give yourself an injection, you should inject the next dose of Humira as soon as you 
remember. Then take your next dose as you would have on your originally scheduled day, had you not 
forgotten a dose.  
 
If you stop using Humira 
 
The decision to stop using Humira should be discussed with your doctor. Your symptoms may return if 
you stop using Humira. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 



418 

4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side 
effects are mild to moderate. However, some may be serious and require treatment. Side effects may occur 
at least up to 4 months after the last Humira injection.  
 
Tell your doctor immediately if you notice any of the following 
 
 severe rash, hives or other signs of allergic reaction  
 swollen face, hands, feet 
 trouble breathing, swallowing 
 shortness of breath with physical activity or upon lying down or swelling of the feet 
 
Tell your doctor as soon as possible if you notice any of the following  
 
 signs of infection such as fever, feeling sick, wounds, dental problems, burning on urination 
 feeling weak or tired 
 coughing 
 tingling 
 numbness 
 double vision 
 arm or leg weakness 
 a bump or open sore that doesn't heal 
 signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, 

paleness 
 
The symptoms described above can be signs of the below listed side effects, which have been observed 
with Humira. 
 
Very common (may affect more than 1 in 10 people)   
 
 injection site reactions (including pain, swelling, redness or itching) 
 respiratory tract infections (including cold, runny nose, sinus infection, pneumonia) 
 headache 
 abdominal pain 
 nausea and vomiting 
 rash 
 musculoskeletal pain 
 
Common (may affect up to 1 in 10 people)  
 
 serious infections (including blood poisoning and influenza) 
 intestinal infections (including gastroenteritis) 
 skin infections (including cellulitis and shingles) 
 ear infections 
 oral infections (including tooth infections and cold sores) 
 reproductive tract infections 
 urinary tract infection 
 fungal infections 
 joint infections 
 benign tumours 



419 

 skin cancer 
 allergic reactions (including seasonal allergy) 
 dehydration 
 mood swings (including depression) 
 anxiety 
 difficulty sleeping 
 sensation disorders such as tingling, prickling or numbness 
 migraine 
 nerve root compression (including low back pain and leg pain) 
 vision disturbances 
 eye inflammation 
 inflammation of the eye lid and eye swelling 
 vertigo (feeling of dizziness or spinning) 
 sensation of heart beating rapidly 
 high blood pressure 
 flushing 
 haematoma (collection of blood outside of blood vessels) 
 cough 
 asthma 
 shortness of breath 
 gastrointestinal bleeding 
 dyspepsia (indigestion, bloating, heart burn) 
 acid reflux disease 
 sicca syndrome (including dry eyes and dry mouth) 
 itching 
 itchy rash 
 bruising 
 inflammation of the skin (such as eczema) 
 breaking of finger nails and toe nails 
 increased sweating 
 hair loss 
 new onset or worsening of psoriasis 
 muscle spasms 
 blood in urine 
 kidney problems 
 chest pain 
 oedema (swelling) 
 fever 
 reduction in blood platelets which increases risk of bleeding or bruising 
 impaired healing 
 
Uncommon (may affect up to 1 in 100 people)   
 
 opportunistic infections (which include tuberculosis and other infections that occur when resistance to 

disease is lowered) 
 neurological infections (including viral meningitis) 
 eye infections 
 bacterial infections 
 diverticulitis (inflammation and infection of the large intestine) 
 cancer 



420 

 cancer that affects the lymph system 
 melanoma 
 immune disorders that could affect the lungs, skin and lymph nodes (most commonly presenting as 

sarcoidosis) 
 vasculitis (inflammation of blood vessels) 
 tremor (shaking) 
 neuropathy (disorder of the nerves) 
 stroke 
 hearing loss, buzzing 
 sensation of heart beating irregularly such as skipped beats 
 heart problems that can cause shortness of breath or ankle swelling 
 heart attack 
 a sac in the wall of a major artery, inflammation and clot of a vein, blockage of a blood vessel 
 lung diseases causing shortness of breath (including inflammation) 
 pulmonary embolism (blockage in an artery of the lung) 
 pleural effusion (abnormal collection of fluid in the pleural space) 
 inflammation of the pancreas which causes severe pain in the abdomen and back 
 difficulty in swallowing 
 facial oedema (swelling of the face) 
 gallbladder inflammation, gallbladder stones 
 fatty liver 
 night sweats 
 scar 
 abnormal muscle breakdown 
 systemic lupus erythematosus (including inflammation of skin, heart, lung, joints and other organ 

systems) 
 sleep interruptions 
 impotence 
 inflammations 
 
Rare (may affect up to 1 in 1,000 people) 
 
 leukaemia (cancer affecting the blood and bone marrow) 
 severe allergic reaction with shock 
 multiple sclerosis 
 nerve disorders (such as eye nerve inflammation and Guillain-Barré syndrome that may cause muscle 

weakness, abnormal sensations, tingling in the arms and upper body) 
 heart stops pumping 
 pulmonary fibrosis (scarring of the lung) 
 intestinal perforation (hole in the intestine) 
 hepatitis 
 reactivation of hepatitis B 
 autoimmune hepatitis (inflammation of the liver caused by the body's own immune system) 
 cutaneous vasculitis (inflammation of blood vessels in the skin) 
 Stevens-Johnson syndrome (early symptoms include malaise, fever, headache and rash) 
 facial oedema (swelling of the face) associated with allergic reactions 
 erythema multiforme (inflammatory skin rash) 
 lupus-like syndrome 
 angioedema (localized swelling of the skin) 
 lichenoid skin reaction (itchy reddish-purple skin rash) 



421 

 
Not known (frequency cannot be estimated from the available data) 
 
 hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal) 
 Merkel cell carcinoma (a type of skin cancer) 
 Kaposi’s sarcoma, a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma 

most commonly appears as purple lesions on the skin 
 liver failure 
 worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle         

weakness) 
 
Some side effects observed with Humira may not have symptoms and may only be discovered through 
blood tests. These include: 
 
Very common (may affect more than 1 in 10 people) 

 
 low blood measurements for white blood cells 
 low blood measurements for red blood cells 
 increased lipids in the blood 
 elevated liver enzymes 
 
Common (may affect up to 1 in 10 people) 
 
 high blood measurements for white blood cells 
 low blood measurements for platelets 
 increased uric acid in the blood 
 abnormal blood measurements for sodium 
 low blood measurements for calcium 
 low blood measurements for phosphate 
 high blood sugar 
 high blood measurements for lactate dehydrogenase 
 autoantibodies present in the blood 
 low blood potassium 
 
Uncommon (may affect up to 1 in 100 people)  
 
 elevated bilirubin measurement (liver blood test) 

 
Rare (may affect up to 1 in 1,000 people) 
 
 low blood measurements for white blood cells, red blood cells and platelet count 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects, you can help provide more information on the safety of this 
medicine. 
 
 
5. How to store Humira 
 
Keep this medicine out of the sight and reach of children.  



422 

 
Do not use this medicine after the expiry date stated on the label/blister/carton after EXP.  
 
Store in a refrigerator (2C – 8C). Do not freeze.  
 
Keep the pre-filled syringe in the outer carton in order to protect from light. 
 
Alternative Storage: 
 
When needed (for example when you are travelling), a single Humira pre-filled syringe may be stored at 
room temperature (up to 25°C) for a maximum period of 14 days – be sure to protect it from light. Once 
removed from the refrigerator for room temperature storage, the syringe must be used within 14 days or 
discarded, even if it is returned to the refrigerator.   
 
You should record the date when the syringe is first removed from refrigerator and the date after which it 
should be discarded. 
 
Do not throw away any medicines via wastewater or household waste. Ask your doctor or pharmacist how 
to throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Humira contains 
 
The active substance is adalimumab. 
The other ingredients are mannitol, polysorbate 80 and water for injections. 
 
What the Humira pre-filled syringe looks like and contents of the pack 
 
Humira 40 mg solution for injection in pre-filled syringe is supplied as a sterile solution of 40 mg 
adalimumab dissolved in 0.4 ml solution. 
 
The Humira pre-filled syringe is a glass syringe containing a solution of adalimumab. Each pack contains 
1, 2, 4 or 6 pre-filled syringes for patient use with 1, 2, 4 or 6 alcohol pads, respectively.   
 
Not all pack sizes may be marketed.   
 
Humira may be available as a vial, a pre-filled syringe and/or a pre-filled pen. 
 
Marketing Authorisation Holder 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 



423 

Manufacturer  
 
AbbVie Biotechnology GmbH 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
AbbVie SA 
Tél/Tel: +32 10  477811 

Lietuva 
AbbVie UAB  
Tel: +370 5 205 3023 

България 
АбВи ЕООД 
Тел.:+359 2 90 30 430 

Luxembourg/Luxemburg 
AbbVie SA 
Belgique/Belgien 
Tél/Tel: +32 10 477811

Česká republika 
AbbVie s.r.o.  
Tel: +420 233 098 111 

Magyarország 
AbbVie Kft. 
Tel.:+36 1 455 8600

Danmark 
AbbVie A/S 
Tlf: +45 72 30-20-28 

Malta 
V.J.Salomone Pharma Limited  
Tel: +356 22983201

Deutschland 
AbbVie Deutschland GmbH & Co. KG 
Tel: 00800 222843 33 (gebührenfrei) 
Tel: +49 (0) 611 / 1720-0

Nederland 
AbbVie B.V. 
Tel:  +31 (0)88 322 2843 

Eesti 
AbbVie Biopharmaceuticals GmbH Eesti filiaal  
Tel: +372 623 1011 

Norge 
AbbVie AS 
Tlf: +47 67 81 80 00

Ελλάδα 
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. 
Τηλ: +30 214 4165 555

Österreich 
AbbVie GmbH  
Tel: +43 1 20589-0

España 
AbbVie Spain, S.L.U. 
Tel:  +34 91 384 09 10 

Polska 
AbbVie Polska Sp. z o.o. 
Tel.: +48 22 372 78 00 

France 
AbbVie 
Tél: +33 (0) 1 45 60 13 00 

Portugal 
AbbVie, Lda.  
Tel: +351 (0)21 1908400 

Hrvatska  
AbbVie d.o.o. 
Tel + 385 (0)1 5625 501

România 
AbbVie S.R.L. 
Tel: +40 21 529 30 35

Ireland 
AbbVie Limited  
Tel: +353 (0)1 4287900

Slovenija 
AbbVie Biofarmacevtska družba d.o.o. 
Tel: +386 (1)32 08 060

Ísland 
Vistor hf. 
Tel: +354 535 7000 

Slovenská republika 
AbbVie s.r.o. 
Tel: +421 2 5050 0777

Italia 
AbbVie S.r.l.  
Tel: +39 06 928921 

Suomi/Finland 
AbbVie Oy  
Puh/Tel:  +358 (0)10 2411 200 



424 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Τηλ.: +357 22 34 74 40

Sverige 
AbbVie AB 
Tel:  +46 (0)8 684 44 600

Latvija 
AbbVie SIA  
Tel: +371 67605000 

United Kingdom 
AbbVie Ltd  
Tel: +44 (0)1628 561090

 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the 
local representative of the Marketing Authorisation Holder. 
 
 
7. Injecting Humira  
 

 The following instructions explain how to give yourself a subcutaneous injection of Humira using 
the pre-filled syringe. First read all the instructions carefully and then follow them step by step.  
 

 You will be instructed by your doctor, nurse or pharmacist on the technique of self-injection.  
 

 Do not attempt to self-inject until you are sure that you understand how to prepare and give the 
injection.  
 

 After proper training, the injection can be given by yourself or given by another person, for 
example, a family member or friend.   
 

 Only use each pre-filled syringe for one injection. 
 
Humira Pre-filled Syringe 
 
          Plunger             Finger Grip          Needle Cover 

 
 

Do not use the pre-filled syringe and call your doctor or pharmacist if the 

 liquid is cloudy, discoloured, or has flakes or particles in it 
 expiry (EXP) date has passed 
 liquid has been frozen or left in direct sunlight 
 pre-filled syringe has been dropped or crushed 

 



425 

Do not remove the needle cover until just before injection. Keep Humira out of the sight and reach 
of children. 
 

STEP 1 
 
Take Humira out of the refrigerator. 
 
Leave Humira at room temperature for 15 to 30 minutes before injecting. 
 

 Do not remove the needle cover while allowing Humira to reach room temperature 
 Do not warm Humira in any other way. For example, do not warm it in a microwave or in hot 

water 
STEP 2  

           Syringe 

 
                 Pad 

Check the expiry (EXP) date. Do not use the pre-filled 
syringe if expiry (EXP) date has passed. 
 
Place the following on a clean, flat surface 
 

 1 single-use pre-filled syringe and  
 1 alcohol pad 

 
Wash and dry your hands. 



426 

STEP 3 
 
Injectable Areas 

     Injectable Areas 

Choose an injection site: 
 

 On the front of your thighs or 
 Your belly (abdomen) at least 5 cm from your belly 

button (navel) 
 At least 3 cm from your last injection site 

 
Wipe the injection site in a circular motion with the alcohol 
pad. 
 

 Do not inject through clothes 
 Do not inject into skin that is sore, bruised, red, 

hard, scarred, has stretch marks, or areas with 
psoriasis plaques 

 
 

STEP 4 

 

Hold the pre-filled syringe in one hand. 
 
Check the liquid in the pre-filled syringe. 
 

 Make sure the liquid is clear and colourless 
 Do not use the pre-filled syringe if the liquid is 

cloudy or has particles 
 Do not use the pre-filled syringe if it has been 

dropped or crushed 
 

Gently pull the needle cover straight off with the other hand. 
Throw the needle cover away. Do not recap. 
 

 Do not touch the needle with your fingers or let the 
needle touch anything 

STEP 5 

 

Hold the pre-filled syringe with the needle facing up. 
 

 Hold the pre-filled syringe at eye level with one 
hand so you can see the air in the pre-filled syringe 

 
Slowly push the plunger in to push the air out through the 
needle.  
 

 It is normal to see a drop of liquid at the end of the 
needle 

 



427 

STEP 6 Hold the body of the pre-filled syringe in one hand between 
the thumb and index fingers, like you would a pencil. 
 
Squeeze the skin at your injection site with your other hand 
to make a raised area and hold it firmly. 

 

STEP 7 

 

Insert the needle all the way into the skin at about a 45-
degree angle with one quick, short motion. 
 

 After the needle is in, let go of the skin you are 
holding  

 
Slowly push the plunger all the way in until all of the liquid 
is injected and the pre-filled syringe is empty. 
 

STEP 8 

 
             Cotton Ball 

When the injection is completed, slowly pull the needle out 
of the skin while keeping the pre-filled syringe at the same 
angle. 
 
After completing the injection, place a cotton ball or gauze 
pad on the skin over the injection site. 
 

 Do not rub 
 Slight bleeding at the injection site is normal 

 

 



428 

STEP 9 
 
Throw away the used pre-filled syringe in a special disposal container as instructed by your doctor, 
nurse or pharmacist. Never recap a needle. 
 

 Do not recycle or throw the pre-filled syringe in the household waste 
 Always keep the pre-filled syringe and the special disposal container out of the sight and 

reach of children 
 

The needle cover, alcohol pad, cotton ball or gauze pad, blister and packaging may be put in your 
household waste. 

 
  



429 

Package leaflet: Information for the patient 
 

Humira 40 mg solution for injection in pre-filled syringe 
adalimumab 

 
Read all of this leaflet carefully before you start using this medicine because it contains important 
information for you. 
 Keep this leaflet. You may need to read it again. 
 Your doctor will also give you a Patient Reminder Card, which contains important safety 

information that you need to be aware of before you begin using Humira and during treatment with 
Humira. Keep this Patient Reminder Card with you. 

 If you have any questions, ask your doctor or pharmacist. 
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even 

if their signs of illness are the same as yours. 
 If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet  
1. What Humira is and what it is used for 
2. What you need to know before you use Humira 
3. How to use Humira 
4. Possible side effects 
5 How to store Humira 
6. Contents of the pack and other information 
7. Injecting Humira 
 
 
1. What Humira is and what it is used for 
 
Humira contains the active substance adalimumab. 
 
Humira is used to treat 

 Rheumatoid arthritis 
 Polyarticular juvenile idiopathic arthritis 
 Enthesitis-related arthritis 
 Ankylosing spondylitis 
 Axial spondyloarthritis without radiographic evidence of ankylosing spondylitis 
 Psoriatic arthritis 
 Plaque psoriasis 
 Hidradenitis suppurativa 
 Crohn’s disease 
 Ulcerative colitis 
 Non-infectious uveitis 
 

The active ingredient in Humira, adalimumab, is a human monoclonal antibody. Monoclonal antibodies 
are proteins that attach to a specific target. 
 
The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the 
immune (defence) system and is present at increased levels in the inflammatory diseases listed above. By 
attaching to TNFα, Humira decreases the process of inflammation in these diseases. 
 



430 

Rheumatoid arthritis 
 
Rheumatoid arthritis is an inflammatory disease of the joints. 
 
Humira is used to treat moderate to severe rheumatoid arthritis in adults. You may first be given other 
disease-modifying medicines, such as methotrexate. If you do not respond well enough to these medicines, 
you will be given Humira. 
 
Humira can also be used to treat severe, active and progressive rheumatoid arthritis without previous 
methotrexate treatment. 
 
Humira can slow down the damage to the joints caused by the inflammatory disease and can help them 
move more freely.  
 
Your doctor will decide if Humira should be used with methotrexate or alone.  
 
Polyarticular juvenile idiopathic arthritis 
 
Polyarticular juvenile idiopathic arthritis is an inflammatory disease of the joints. 
 
Humira is used to treat polyarticular juvenile idiopathic arthritis in patients from 2 years of age. You may 
first be given other disease-modifying medicines, such as methotrexate. If you do not respond well enough 
to these medicines, you will be given Humira. 
 
Your doctor will decide if Humira should be used with methotrexate or alone. 
 
Enthesitis-related arthritis 
 
Enthesitis-related arthritis is an inflammatory disease of the joints and the places where tendons join the 
bone. 
 
Humira is used to treat enthesitis-related arthritis in patients from 6 years of age. You may first be given 
other disease-modifying medicines, such as methotrexate. If you do not respond well enough to these 
medicines, you will be given Humira. 
 
Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing 
spondylitis 
 
Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing 
spondylitis are inflammatory diseases of the spine. 
 
Humira is used to treat severe ankylosing spondylitis and axial spondyloarthritis without radiographic 
evidence of ankylosing spondylitis in adults. You may first be given other medicines. If you do not 
respond well enough to these medicines, you will be given Humira. 
 
Psoriatic arthritis 
 
Psoriatic arthritis is an inflammatory disease of the joints that is usually associated with psoriasis. 
 
Humira is used to treat psoriatic arthritis in adults. Humira can slow down the damage to the joints caused 
by the disease and can help them move more freely. You may first be given other medicines. If you do not 
respond well enough to these medicines, you will be given Humira. 
 



431 

Plaque psoriasis  
 
Plaque psoriasis is a skin condition that causes red, flaky, crusty patches of skin covered with silvery 
scales. Plaque psoriasis can also affect the nails, causing them to crumble, become thickened and lift away 
from the nail bed which can be painful.   
 
Humira is used to treat 

 moderate to severe chronic plaque psoriasis in adults and  
 severe chronic plaque psoriasis in children and adolescents aged 4 to 17 years for whom topical 

therapy and phototherapies have either not worked very well or are not suitable. 
 

Hidradenitis suppurativa 
 
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic and often painful inflammatory skin 
disease. Symptoms may include tender nodules (lumps) and abscesses (boils) that may leak pus. It most 
commonly affects specific areas of the skin, such as under the breasts, the armpits, inner thighs, groin and 
buttocks. Scarring may also occur in affected areas. 
 
Humira is used to treat  

 moderate to severe hidradenitis suppurativa in adults and 
 moderate to severe hidradenitis suppurativa in adolescents aged 12 to 17 years.  

 
Humira can reduce the number of nodules and abscesses caused by the disease and the pain that is often 
associated with the disease. You may first be given other medicines. If you do not respond well enough to 
these medicines, you will be given Humira. 
 
Crohn’s disease 
 
Crohn’s disease is an inflammatory disease of the digestive tract. 
 
Humira is used to treat 

 moderate to severe Crohn’s disease in adults and  
 moderate to severe Crohn’s disease in children and adolescents aged 6 to 17 years 

 
You may first be given other medicines. If you do not respond well enough to these medicines, you will be 
given Humira. 
 
Ulcerative colitis 
 
Ulcerative colitis is an inflammatory disease of the large intestine. 
 
Humira is used to treat  

 moderate to severe ulcerative colitis in adults and  
 moderate to severe ulcerative colitis in children and adolescents aged 6 to 17 years 

 
You may first be given other medicines. If you do not respond well enough to these medicines, you will be 
given Humira. 
 
Non-infectious uveitis 
 
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. 
 
Humira is used to treat  



432 

 adults with non-infectious uveitis with inflammation affecting the back of the eye 
 children with chronic non-infectious uveitis from 2 years of age with inflammation affecting the 

front of the eye  
 
This inflammation may lead to a decrease of vision and/or the presence of floaters in the eye (black dots or 
wispy lines that move across the field of vision). Humira works by reducing this inflammation. 
 
You may first be given other medicines. If you do not respond well enough to these medicines, you will be 
given Humira. 
 
 
2. What you need to know before you use Humira 
 
Do not use Humira: 
 

 If you are allergic to adalimumab or any of the other ingredients of this medicine (listed in section 
6).  

 
 If you have active tuberculosis or other severe infections (see “Warnings and precautions”). It is 

important that you tell your doctor if you have symptoms of infections, for example, fever, 
wounds, feeling tired, dental problems. 

 
 If you have moderate or severe heart failure. It is important to tell your doctor if you have had or 

have a serious heart condition (see “Warnings and precautions”). 
 
Warnings and precautions 
 
Talk to your doctor or pharmacist before using Humira. 
 
Allergic reactions 
 

 If you get allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling 
or rash do not inject more Humira and contact your doctor immediately since, in rare cases, these 
reactions can be life threatening. 

 
Infections 
 

 If you have an infection, including long-term infection or an infection in one part of the body (for 
example, leg ulcer) consult your doctor before starting Humira. If you are unsure, contact your 
doctor.  

 
 You might get infections more easily while you are receiving Humira treatment. This risk may 

increase if you have problems with your lungs. These infections may be serious and include:  
 tuberculosis 
 infections caused by viruses, fungi, parasites or bacteria 
 severe infection in the blood (sepsis) 

 
In rare cases, these infections can be life-threatening. It is important to tell your doctor if you get 
symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may tell you to 
stop using Humira for some time. 
 



433 

 Tell your doctor if you live or travel in regions where fungal infections (for example, 
histoplasmosis, coccidioidomycosis or blastomycosis) are very common. 

 
 Tell your doctor if you have had infections which keep coming back or other conditions that 

increase the risk of infections. 
 

 If you are over 65 years you may be more likely to get infections while taking Humira. You and 
your doctor should pay special attention to signs of infection while you are being treated with 
Humira. It is important to tell your doctor if you get symptoms of infections, such as fever, 
wounds, feeling tired or dental problems. 

 
Tuberculosis 
 

 It is very important that you tell your doctor if you have ever had tuberculosis, or if you have been 
in close contact with someone who has had tuberculosis. If you have active tuberculosis, do not 
use Humira. 

 
 As cases of tuberculosis have been reported in patients treated with Humira, your doctor 

will check you for signs and symptoms of tuberculosis before starting Humira. This will 
include a thorough medical evaluation including your medical history and appropriate 
screening tests (for example, chest X-ray and a tuberculin test). The conduct and results of 
these tests should be recorded on your Patient Reminder Card.  

 Tuberculosis can develop during therapy even if you have received treatment for the 
prevention of tuberculosis.  

 If symptoms of tuberculosis (for example, cough that does not go away, weight loss, lack 
of energy, mild fever), or any other infection appear during or after therapy tell your 
doctor immediately. 
 

Hepatitis B 
 

 Tell your doctor if you are a carrier of the hepatitis B virus (HBV), if you have active HBV or if 
you think you might be at risk of getting HBV.  

 Your doctor should test you for HBV. In people who carry HBV, Humira can cause the 
virus to become active again. 

 In some rare cases, especially if you are taking other medicines that suppress the immune 
system, reactivation of HBV can be life-threatening.   

 
Surgery or dental procedure 
 

 If you are about to have surgery or dental procedures, please inform your doctor that you are 
taking Humira. Your doctor may recommend temporary discontinuation of Humira.  

 
Demyelinating disease 
 

 If you have or develop a demyelinating disease (a disease that affects the insulating layer around 
the nerves, such as multiple sclerosis), your doctor will decide if you should receive or continue to 
receive Humira. Tell your doctor immediately if you experience symptoms like changes in your 
vision, weakness in your arms or legs or numbness or tingling in any part of your body. 

 
Vaccinations 
 

 Certain vaccines may cause infections and should not be given while receiving Humira.  



434 

 
 Check with your doctor before you receive any vaccines.  
 It is recommended that children, if possible, be given all the scheduled vaccinations for 

their age before they start treatment with Humira. 
 If you received Humira while you were pregnant, your baby may be at higher risk for 

getting such an infection for up to approximately five months after the last Humira dose 
you received during pregnancy. It is important that you tell your baby's doctors and other 
health care professionals about your Humira use during your pregnancy so they can 
decide when your baby should receive any vaccine. 

 
Heart failure 
 

 If you have mild heart failure and are being treated with Humira, your heart failure status must be 
closely monitored by your doctor. It is important to tell your doctor if you have had or have a 
serious heart condition. If you develop new or worsening symptoms of heart failure (e.g. shortness 
of breath, or swelling of your feet), you must contact your doctor immediately. Your doctor will 
decide if you should receive Humira. 

 
Fever, bruising, bleeding or looking pale 
 

 In some patients the body may fail to produce enough of the blood cells that fight off 
infections or help you to stop bleeding. Your doctor may decide to stop treatment. If you 
develop a fever that does not go away, develop light bruises or bleed very easily or look very 
pale, call your doctor right away. 

 
Cancer 
 

 There have been very rare cases of certain kinds of cancer in children and adult patients taking 
Humira or other TNF blockers.   

 
 People with more serious rheumatoid arthritis that have had the disease for a long time 

may have a higher than average risk of getting lymphoma (a cancer that affects the lymph 
system) and leukaemia (a cancer that affects the blood and bone marrow).  

 If you take Humira the risk of getting lymphoma, leukaemia, or other cancers may 
increase. On rare occasions, an uncommon and severe type of lymphoma, has been seen in 
patients taking Humira. Some of those patients were also treated with azathioprine or 6-
mercaptopurine.  

 Tell your doctor if you are taking azathioprine or 6-mercaptopurine with Humira.  
 Cases of non-melanoma skin cancer have been observed in patients taking Humira.  
 If new skin lesions appear during or after therapy or if existing lesions change appearance, 

tell your doctor. 
 

 There have been cases of cancers, other than lymphoma in patients with a specific type of lung 
disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another TNF blocker. 
If you have COPD, or are a heavy smoker, you should discuss with your doctor whether treatment 
with a TNF blocker is appropriate for you. 

 
Autoimmune disease 
 

 On rare occasions, treatment with Humira could result in lupus-like syndrome. Contact your 
doctor if symptoms such as persistent unexplained rash, fever, joint pain or tiredness occur. 

 



435 

Children and adolescents 
 

 Vaccinations: if possible, children should be up to date with all vaccinations before using Humira. 
 

Other medicines and Humira 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 
 
You should not take Humira with medicines containing the following active substances due to increased 
risk of serious infection: 

 anakinra 
 abatacept. 

 
Humira can be taken together with: 

 methotrexate 
 certain disease-modifying anti-rheumatic agents (for example, sulfasalazine, hydroxychloroquine, 

leflunomide and injectable gold preparations) 
 steroids or pain medications including non-steroidal anti-inflammatory drugs (NSAIDs). 

 
If you have questions, please ask your doctor. 
 
Pregnancy and breast-feeding 
 

 You should consider the use of adequate contraception to prevent pregnancy and continue its use 
for at least 5 months after the last Humira treatment. 

 If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for 
advice about taking this medicine. 

 Humira should only be used during a pregnancy if needed. 
 According to a pregnancy study, there was no higher risk of birth defects when the mother had 

received Humira during pregnancy compared with mothers with the same disease who did not 
receive Humira. 

 Humira can be used during breast-feeding. 
 If you receive Humira during your pregnancy, your baby may have a higher risk for getting an 

infection. 
 It is important that you tell your baby’s doctors and other health care professionals about your 

Humira use during your pregnancy before the baby receives any vaccine. For more information on 
vaccines see the “Warnings and precautions” section. 

 
Driving and using machines 
 
Humira may have a small effect on your ability to drive, cycle or use machines. Room spinning sensation 
and vision disturbances may occur after taking Humira. 
 
 
3. How to use Humira 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are not sure.  
 
The recommended doses for Humira in each of the approved uses are shown in the following table.  
Your doctor may prescribe another strength of Humira if you need a different dose. 
 



436 

Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or axial spondyloarthritis 
without radiographic evidence of ankylosing spondylitis 
Age or body weight How much and how often to 

take?
Notes 

Adults  40 mg every other week In rheumatoid arthritis, 
methotrexate is continued while 
using Humira. If your doctor 
decides that methotrexate is 
inappropriate, Humira can be 
given alone. 
 
If you have rheumatoid arthritis 
and you do not receive 
methotrexate with your Humira 
therapy, your doctor may decide 
to give Humira 40 mg every 
week or 80 mg every other 
week. 

 
Polyarticular juvenile idiopathic arthritis
Age or body weight How much and how often to 

take?
Notes 

Children, adolescents and adults 
from 2 years of age weighing 30 
kg or more 

40 mg every other week Not applicable 

Children and adolescents from 2 
years of age weighing 10 kg to 
less than 30 kg 

20 mg every other week  Not applicable 

 
Enthesitis-related arthritis 
Age or body weight How much and how often to 

take?
Notes 

Children, adolescents and adults 
from 6 years of age weighing 30 
kg or more 

40 mg every other week  Not applicable 

Children and adolescents from 6 
years of age weighing 15 kg to 
less than 30 kg 

20 mg every other week Not applicable 

 
Plaque psoriasis 
Age or body weight How much and how often to 

take?
Notes 

Adults  
 

First dose of 80 mg (two 40 mg 
injections in one day), followed 
by 40 mg every other week 
starting one week after the first 
dose. 

If you have an inadequate 
response, your doctor may 
increase the dosage to 40 mg 
every week or 80 mg every 
other week. 



437 

Children and adolescents from 4 
to 17 years of age weighing 30 
kg or more 

First dose of 40 mg, followed by 
40 mg one week later. 
 
Thereafter, the usual dose is 40 
mg every other week.

Not applicable 

Children and adolescents from 4 
to 17 years of age weighing 15 
kg to less than 30 kg 

First dose of 20 mg, followed by 
20 mg one week later. 
 
Thereafter, the usual dose is 20 
mg every other week.

Not applicable 

 
Hidradenitis suppurativa 
Age or body weight How much and how often to 

take?
Notes 

Adults  First dose of 160 mg (four 40 
mg injections in one day or two 
40 mg injections per day for two 
consecutive days), followed by 
an 80 mg dose (two 40 mg 
injections in one day) two 
weeks later. After two further 
weeks, continue with a dose of 
40 mg every week or 80 mg 
every other week, as prescribed 
by your doctor.  

It is recommended that you use 
an antiseptic wash daily on the 
affected areas. 
 

Adolescents from 12 to 17 years 
of age weighing 30 kg or more 

First dose of 80 mg (two 40 mg 
injections in one day), followed 
by 40 mg every other week 
starting one week later.   

If you have an inadequate 
response to Humira 40 mg every 
other week, your doctor may 
increase the dosage to 40 mg 
every week or 80 mg every 
other week.  
It is recommended that you use 
an antiseptic wash daily on the 
affected areas. 

 



438 

Crohn’s disease 
Age or body weight How much and how often to 

take?
Notes 

Children, adolescents and adults 
from 6 years of age weighing 40 
kg or more 

First dose of 80 mg (two 40 mg 
injections in one day), followed 
by 40 mg two weeks later. 
 
If a faster response is required, 
the doctor may prescribe a first 
dose of 160 mg (four 40 mg 
injections in one day or two 40 
mg injections per day for two 
consecutive days), followed by 
80 mg (two 40 mg injections in 
one day) two weeks later. 
 
Thereafter, the usual dose is 40 
mg every other week.

Your doctor may increase the 
dosage to 40 mg every week or 
80 mg every other week. 
 

Children and adolescents from 6 
to 17 years of age weighing less 
than 40 kg 

First dose of 40 mg, followed by 
20 mg two weeks later.  
 
If a faster response is required, 
the doctor may prescribe a first 
dose of 80 mg (two 40 mg 
injections in one day), followed 
by 40 mg two weeks later. 
 
Thereafter, the usual dose is 20 
mg every other week.

Your doctor may increase the 
dose frequency to 20 mg every 
week. 
 

 
Ulcerative colitis 
Age or body weight How much and how often to 

take?
Notes 

Adults First dose of 160 mg (four 40 
mg injections in one day or two 
40 mg injections per day for two 
consecutive days), followed by 
80 mg (two 40 mg injections in 
one day) two weeks later. 
 
Thereafter, the usual dose is 
40 mg every other week.

Your doctor may increase the 
dosage to 40 mg every week or 
80 mg every other week. 

Children and adolescents from 6 
years of age weighing less than 
40 kg 

First dose of 80 mg (two 40 mg 
injections in one day), followed 
by 40 mg (one 40 mg injection) 
two weeks later. 
 
Thereafter, the usual dose is 40 
mg every other week.

You should continue taking 
Humira at your usual dose, even 
after turning 18 years of age. 

Children and adolescents from 6 
years of age weighing 40 kg or 
more 

First dose of 160 mg (four 40 
mg injections in one day or two 
40 mg injections per day for two 
consecutive days), followed by 

You should continue taking 
Humira at your usual dose, even 
after turning 18 years of age. 



439 

80 mg (two 40 mg injections in 
one day) two weeks later. 
 
Thereafter, the usual dose is 80 
mg every other week.

 
Non-infectious uveitis 
Age or body weight How much and how often to 

take?
Notes 

Adults First dose of 80 mg (two 40 mg 
injections in one day), followed 
by 40 mg every other week 
starting one week after the first 
dose.

Corticosteroids or other 
medicines that influence the 
immune system may be 
continued while using Humira. 
Humira can also be given alone.

Children and adolescents from 
2 years of age weighing less 
than 30 kg 
 

20 mg every other week Your doctor may prescribe an 
initial dose of 40 mg to be 
administered one week prior to 
the start of the usual dose of 
20 mg every other week. 
Humira is recommended for use 
in combination with 
methotrexate. 

Children and adolescents from 
2 years of age weighing at least 
30 kg 
 

40 mg every other week  Your doctor may prescribe an 
initial dose of 80 mg to be 
administered one week prior to 
the start of the usual dose of 
40 mg every other week. 
Humira is recommended for use 
in combination with 
methotrexate. 

 
Method and route of administration 
 
Humira is administered by injection under the skin (by subcutaneous injection). 
 
Detailed instructions on how to inject Humira are provided in section 7 ‘Injecting Humira’. 
 
If you use more Humira than you should 
 
If you accidentally inject Humira more frequently than told to by your doctor or pharmacist, call your 
doctor or pharmacist and tell them that you have taken more. Always take the outer carton of the medicine 
with you, even if it is empty.  
 
If you forget to use Humira 
 
If you forget to give yourself an injection, you should inject the next dose of Humira as soon as you 
remember. Then take your next dose as you would have on your originally scheduled day, had you not 
forgotten a dose.  
 
If you stop using Humira 
 
The decision to stop using Humira should be discussed with your doctor. Your symptoms may return if 
you stop using Humira. 



440 

 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side 
effects are mild to moderate. However, some may be serious and require treatment. Side effects may occur 
at least up to 4 months after the last Humira injection.  
 
Tell your doctor immediately if you notice any of the following 
 
 severe rash, hives or other signs of allergic reaction  
 swollen face, hands, feet 
 trouble breathing, swallowing 
 shortness of breath with physical activity or upon lying down or swelling of the feet 

 
Tell your doctor as soon as possible if you notice any of the following 
 
 signs of infection such as fever, feeling sick, wounds, dental problems, burning on urination 
 feeling weak or tired 
 coughing 
 tingling 
 numbness 
 double vision 
 arm or leg weakness 
 a bump or open sore that doesn't heal 
 signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, 

paleness 
 
The symptoms described above can be signs of the below listed side effects, which have been observed 
with Humira. 
 
Very common (may affect more than 1 in 10 people)   
 
 injection site reactions (including pain, swelling, redness or itching) 
 respiratory tract infections (including cold, runny nose, sinus infection, pneumonia) 
 headache 
 abdominal pain 
 nausea and vomiting 
 rash 
 musculoskeletal pain 
 
Common (may affect up to 1 in 10 people)  
 
 serious infections (including blood poisoning and influenza) 
 intestinal infections (including gastroenteritis) 
 skin infections (including cellulitis and shingles) 
 ear infections 
 oral infections (including tooth infections and cold sores) 
 reproductive tract infections 



441 

 urinary tract infection 
 fungal infections 
 joint infections 
 benign tumours 
 skin cancer 
 allergic reactions (including seasonal allergy) 
 dehydration 
 mood swings (including depression) 
 anxiety 
 difficulty sleeping 
 sensation disorders such as tingling, prickling or numbness 
 migraine 
 nerve root compression (including low back pain and leg pain) 
 vision disturbances 
 eye inflammation 
 inflammation of the eye lid and eye swelling 
 vertigo (feeling of dizziness or spinning) 
 sensation of heart beating rapidly 
 high blood pressure 
 flushing 
 haematoma (collection of blood outside of blood vessels) 
 cough 
 asthma 
 shortness of breath 
 gastrointestinal bleeding 
 dyspepsia (indigestion, bloating, heart burn) 
 acid reflux disease 
 sicca syndrome (including dry eyes and dry mouth) 
 itching 
 itchy rash 
 bruising 
 inflammation of the skin (such as eczema) 
 breaking of finger nails and toe nails 
 increased sweating 
 hair loss 
 new onset or worsening of psoriasis 
 muscle spasms 
 blood in urine 
 kidney problems 
 chest pain 
 oedema (swelling) 
 fever 
 reduction in blood platelets which increases risk of bleeding or bruising 
 impaired healing 
 
Uncommon (may affect up to 1 in 100 people)   
 
 opportunistic infections (which include tuberculosis and other infections that occur when resistance 

to disease is lowered) 
 neurological infections (including viral meningitis) 



442 

 eye infections 
 bacterial infections 
 diverticulitis (inflammation and infection of the large intestine) 
 cancer 
 cancer that affects the lymph system 
 melanoma 
 immune disorders that could affect the lungs, skin and lymph nodes (most commonly presenting as 

sarcoidosis) 
 vasculitis (inflammation of blood vessels) 
 tremor (shaking) 
 neuropathy (disorder of the nerves) 
 stroke 
 hearing loss, buzzing 
 sensation of heart beating irregularly such as skipped beats 
 heart problems that can cause shortness of breath or ankle swelling 
 heart attack 
 a sac in the wall of a major artery, inflammation and clot of a vein, blockage of a blood vessel 
 lung diseases causing shortness of breath (including inflammation) 
 pulmonary embolism (blockage in an artery of the lung) 
 pleural effusion (abnormal collection of fluid in the pleural space) 
 inflammation of the pancreas which causes severe pain in the abdomen and back 
 difficulty in swallowing 
 facial oedema (swelling of the face) 
 gallbladder inflammation, gallbladder stones 
 fatty liver 
 night sweats 
 scar 
 abnormal muscle breakdown 
 systemic lupus erythematosus (including inflammation of skin, heart, lung, joints and other organ 

systems) 
 sleep interruptions 
 impotence 
 inflammations 
 
Rare (may affect up to 1 in 1,000 people) 
 
 leukaemia (cancer affecting the blood and bone marrow) 
 severe allergic reaction with shock 
 multiple sclerosis 
 nerve disorders (such as eye nerve inflammation and Guillain-Barré syndrome that may cause 

muscle weakness, abnormal sensations, tingling in the arms and upper body) 
 heart stops pumping 
 pulmonary fibrosis (scarring of the lung) 
 intestinal perforation (hole in the intestine) 
 hepatitis 
 reactivation of hepatitis B 
 autoimmune hepatitis (inflammation of the liver caused by the body's own immune system) 
 cutaneous vasculitis (inflammation of blood vessels in the skin) 
 Stevens-Johnson syndrome (early symptoms include malaise, fever, headache and rash) 
 facial oedema (swelling of the face) associated with allergic reactions 



443 

 erythema multiforme (inflammatory skin rash) 
 lupus-like syndrome 
 angioedema (localized swelling of the skin) 
 lichenoid skin reaction (itchy reddish-purple skin rash) 
 
Not known (frequency cannot be estimated from the available data) 
 
 hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal) 
 Merkel cell carcinoma (a type of skin cancer) 
 Kaposi’s sarcoma, a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma 

most commonly appears as purple lesions on the skin 
 liver failure 
 worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle         

weakness) 
 
Some side effects observed with Humira may not have symptoms and may only be discovered through 
blood tests. These include: 
 
Very common (may affect more than 1 in 10 people) 
 
 low blood measurements for white blood cells 
 low blood measurements for red blood cells 
 increased lipids in the blood 
 elevated liver enzymes 
 
Common (may affect up to 1 in 10 people) 
 
 high blood measurements for white blood cells 
 low blood measurements for platelets 
 increased uric acid in the blood 
 abnormal blood measurements for sodium 
 low blood measurements for calcium 
 low blood measurements for phosphate 
 high blood sugar 
 high blood measurements for lactate dehydrogenase 
 autoantibodies present in the blood 
 low blood potassium 
 
Uncommon (may affect up to 1 in 100 people)  
 
 elevated bilirubin measurement (liver blood test) 
 
Rare (may affect up to 1 in 1,000 people) 
 
 low blood measurements for white blood cells, red blood cells and platelet count 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V.  By reporting side effects, you can help provide more information on the safety of this 
medicine. 
 



444 

 
5. How to store Humira 
 
Keep this medicine out of the sight and reach of children.  
 
Do not use this medicine after the expiry date stated on the label/blister/carton after EXP.  
 
Store in a refrigerator (2C – 8C). Do not freeze.  
 
Keep the pre-filled syringe in the outer carton in order to protect from light.   
 
Alternative Storage: 
 
When needed (for example, when you are travelling), a single Humira pre-filled syringe may be stored at 
room temperature (up to 25°C) for a maximum period of 14 days – be sure to protect it from light. Once 
removed from the refrigerator for room temperature storage, the syringe must be used within 14 days or 
discarded, even if it is returned to the refrigerator.   
 
You should record the date when the syringe is first removed from refrigerator and the date after which it 
should be discarded. 
 
Do not throw away any medicines via wastewater or household waste. Ask your doctor or pharmacist how 
to throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Humira contains 
 
The active substance is adalimumab. 
The other ingredients are mannitol, polysorbate 80 and water for injections. 
 
What the Humira pre-filled syringe with automatic needle guard looks like and contents of the pack 
 
Humira 40 mg solution for injection in pre-filled syringe with automatic needle guard is supplied as a 
sterile solution of 40 mg adalimumab dissolved in 0.4 ml solution. 
 
The Humira pre-filled syringe is a glass syringe containing a solution of adalimumab.  
 
Each pack contains 1, 2 or 6 pre-filled syringes for patient use with 1, 2 or 6 alcohol pads, respectively.   
 
Not all pack sizes may be marketed.   
 
Humira may be available as a vial, a pre-filled syringe and/or a pre-filled pen. 
 
Marketing Authorisation Holder 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 
Manufacturer  



445 

 
AbbVie Biotechnology GmbH 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
AbbVie SA 
Tél/Tel: +32 10  477811 

Lietuva 
AbbVie UAB  
Tel: +370 5 205 3023 

България 
АбВи ЕООД 
Тел.:+359 2 90 30 430 

Luxembourg/Luxemburg 
AbbVie SA 
Belgique/Belgien 
Tél/Tel: +32 10 477811

Česká republika 
AbbVie s.r.o.  
Tel: +420 233 098 111 

Magyarország 
AbbVie Kft. 
Tel.:+36 1 455 8600

Danmark 
AbbVie A/S 
Tlf: +45 72 30-20-28 

Malta 
V.J.Salomone Pharma Limited  
Tel: +356 22983201

Deutschland 
AbbVie Deutschland GmbH & Co. KG 
Tel: 00800 222843 33 (gebührenfrei) 
Tel: +49 (0) 611 / 1720-0

Nederland 
AbbVie B.V. 
Tel:  +31 (0)88 322 2843 

Eesti 
AbbVie Biopharmaceuticals GmbH Eesti filiaal  
Tel: +372 623 1011 

Norge 
AbbVie AS 
Tlf: +47 67 81 80 00

Ελλάδα 
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. 
Τηλ: +30 214 4165 555 

Österreich 
AbbVie GmbH  
Tel: +43 1 20589-0 

España 
AbbVie Spain, S.L.U. 
Tel:  +34 91 384 09 10 

Polska 
AbbVie Polska Sp. z o.o. 
Tel.: +48 22 372 78 00 

France 
AbbVie 
Tél: +33 (0) 1 45 60 13 00 

Portugal 
AbbVie, Lda.  
Tel: +351 (0)21 1908400

Hrvatska  
AbbVie d.o.o. 
Tel + 385 (0)1 5625 501

România 
AbbVie S.R.L. 
Tel: +40 21 529 30 35

Ireland 
AbbVie Limited  
Tel: +353 (0)1 4287900

Slovenija 
AbbVie Biofarmacevtska družba d.o.o. 
Tel: +386 (1)32 08 060

Ísland 
Vistor hf. 
Tel: +354 535 7000 

Slovenská republika 
AbbVie s.r.o. 
Tel: +421 2 5050 0777

Italia 
AbbVie S.r.l.  
Tel: +39 06 928921 

Suomi/Finland 
AbbVie Oy  
Puh/Tel:  +358 (0)10 2411 200 

Κύπρος 
Lifepharma (Z.A.M.) Ltd

Sverige 
AbbVie AB



446 

Τηλ.: +357 22 34 74 40 Tel:  +46 (0)8 684 44 600
Latvija 
AbbVie SIA  
Tel: +371 67605000 

United Kingdom 
AbbVie Ltd  
Tel: +44 (0)1628 561090

 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the 
local representative of the Marketing Authorisation Holder. 
 
 
7. Injecting Humira  
 

 The following instructions explain how to give yourself a subcutaneous injection of Humira using 
the pre-filled syringe. First read all the instructions carefully and then follow them step by step.  
 

 You will be instructed by your doctor, nurse or pharmacist on the technique of self-injection.  
 

 Do not attempt to self-inject until you are sure that you understand how to prepare and give the 
injection.  
 

 After proper training, the injection can be given by yourself or given by another person, for 
example, a family member or friend.   
 

 Only use each pre-filled syringe for one injection. 
 
Humira Pre-filled Syringe 
 
      Plunger    Finger Grip      Needle Cover 

 
 
Do not use the pre-filled syringe and call your doctor or pharmacist if the 
 

 liquid is cloudy, discoloured, or has flakes or particles in it 
 expiry (EXP) date has passed 
 liquid has been frozen or left in direct sunlight 
 pre-filled syringe has been dropped or crushed 

 



447 

Do not remove the needle cover until just before injection. Keep Humira out of the sight and reach 
of children. 
 

STEP 1 
 
Take Humira out of the refrigerator. 
 
Leave Humira at room temperature for 15 to 30 minutes before injecting. 
 

 Do not remove the needle cover while allowing Humira to reach room temperature 
 Do not warm Humira in any other way. For example, do not warm it in a microwave or in hot 

water 
STEP 2  
 
           Syringe 

                 Pad 

Check the expiry (EXP) date. Do not use the pre-filled 
syringe if expiry (EXP) date has passed. 
 
Place the following on a clean, flat surface 
 

 1 single-use pre-filled syringe and  
 1 alcohol pad 

 
Wash and dry your hands. 

STEP 3 
 
Injectable Areas 

     Injectable Areas 

Choose an injection site: 
 

 On the front of your thighs or 
 Your belly (abdomen) at least 5 cm from your belly 

button (navel) 
 At least 3 cm from your last injection site 

 
Wipe the injection site in a circular motion with the alcohol 
pad. 
 

 Do not inject through clothes 
 Do not inject into skin that is sore, bruised, red, 

hard, scarred, has stretch marks, or areas with 
psoriasis plaques 

 
 

STEP 4 Hold the pre-filled syringe in one hand between the finger 
grip and the needle cover. 
 
Check the liquid in the pre-filled syringe. 



448 

 

 Make sure the liquid is clear and colourless 
 Do not use the pre-filled syringe if the liquid is 

cloudy or has particles 
 Do not use the pre-filled syringe if it has been 

dropped or crushed 
 

Gently pull the needle cover straight off with the other hand. 
Throw the needle cover away. Do not recap. 
 

 Do not hold or pull the plunger when removing the 
needle cover 

 Do not touch the needle with your fingers or let the 
needle touch anything 

 It is normal to see a drop of liquid at the end of the 
needle

STEP 5 Hold the body of the pre-filled syringe in one hand between 
the thumb and index fingers, like you would a pencil. 
 
Squeeze the skin at your injection site with your other hand 
to make a raised area and hold it firmly. 

 



449 

STEP 6 Insert the needle all the way into the skin at about a 45-
degree angle with one quick, short motion. 
 

 After the needle is in, let go of the skin you are 
holding  

 
Slowly push the plunger all the way in until all of the liquid 
is injected and the pre-filled syringe is empty. 
 

STEP 7 

 

When the injection is completed, slowly pull the needle out 
of the skin while keeping the pre-filled syringe at the same 
angle. 
 
Slowly take your thumb off the plunger. The needle will 
then be covered by the automatic needle guard.  
 The automatic needle guard will not activate unless all the 

liquid is injected 

 Speak to your doctor, pharmacist or nurse if you think 
you have not given a full dose  

After completing the injection, place a cotton ball or gauze 
pad on the skin over the injection site. 
 

 Do not rub 
 Slight bleeding at the injection site is normal 

 
STEP 8 
 
Throw away the used pre-filled syringe in a special disposal container as instructed by your doctor, 
nurse or pharmacist. Never recap a needle. 
 

 Do not recycle or throw the pre-filled syringe in the household waste 
 Always keep the pre-filled syringe and the special disposal container out of the sight and 

reach of children 
 

The needle cover, alcohol pad, cotton ball or gauze pad, blister and packaging may be put in your 
household waste. 

 



450 

Package leaflet: Information for the patient 
 

Humira 40 mg solution for injection in pre-filled pen 
adalimumab 

 
Read all of this leaflet carefully before you start using this medicine because it contains important 
information for you. 
 Keep this leaflet. You may need to read it again. 
 Your doctor will also give you a Patient Reminder Card, which contains important safety 

information that you need to be aware of before you begin using Humira and during treatment with 
Humira. Keep this Patient Reminder Card with you. 

 If you have any questions, ask your doctor or pharmacist. 
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even 

if their signs of illness are the same as yours. 
 If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet  
1. What Humira is and what it is used for 
2. What you need to know before you use Humira 
3. How to use Humira 
4. Possible side effects 
5 How to store Humira 
6. Contents of the pack and other information 
7. Injecting Humira 
 
 
1. What Humira is and what it is used for 
 
Humira contains the active substance adalimumab. 
 
Humira is used to treat 

 Rheumatoid arthritis 
 Polyarticular juvenile idiopathic arthritis 
 Enthesitis-related arthritis 
 Ankylosing spondylitis 
 Axial spondyloarthritis without radiographic evidence of ankylosing spondylitis 
 Psoriatic arthritis 
 Plaque psoriasis 
 Hidradenitis suppurativa 
 Crohn’s disease 
 Ulcerative colitis 
 Non-infectious uveitis 

 
The active ingredient in Humira, adalimumab, is a human monoclonal antibody. Monoclonal antibodies 
are proteins that attach to a specific target. 
 
The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the 
immune (defence) system and is present at increased levels in the inflammatory diseases listed above. By 
attaching to TNFα, Humira decreases the process of inflammation in these diseases. 
 



451 

Rheumatoid arthritis 
 
Rheumatoid arthritis is an inflammatory disease of the joints. 
 
Humira is used to treat moderate to severe rheumatoid arthritis in adults. You may first be given other 
disease-modifying medicines, such as methotrexate. If you do not respond well enough to these medicines, 
you will be given Humira. 
 
Humira can also be used to treat severe, active and progressive rheumatoid arthritis without previous 
methotrexate treatment. 
 
Humira can slow down the damage to the joints caused by the inflammatory disease and can help them 
move more freely.  
 
Your doctor will decide if Humira should be used with methotrexate or alone.  
 
Polyarticular juvenile idiopathic arthritis 
 
Polyarticular juvenile idiopathic arthritis is an inflammatory disease of the joints. 
 
Humira is used to treat polyarticular juvenile idiopathic arthritis in patients from 2 years of age. You may 
first be given other disease-modifying medicines, such as methotrexate. If you do not respond well enough 
to these medicines, you will be given Humira. 
 
Your doctor will decide if Humira should be used with methotrexate or alone. 
 
Enthesitis-related arthritis 
 
Enthesitis-related arthritis is an inflammatory disease of the joints and the places where tendons join the 
bone. 
 
Humira is used to treat enthesitis-related arthritis in patients from 6 years of age. You may first be given 
other disease-modifying medicines, such as methotrexate. If you do not respond well enough to these 
medicines, you will be given Humira. 
 
Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing 
spondylitis 
 
Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing 
spondylitis are inflammatory diseases of the spine. 
 
Humira is used to treat severe ankylosing spondylitis and axial spondyloarthritis without radiographic 
evidence of ankylosing spondylitis in adults. You may first be given other medicines. If you do not 
respond well enough to these medicines, you will be given Humira. 
 
Psoriatic arthritis 
 
Psoriatic arthritis is an inflammatory disease of the joints that is usually associated with psoriasis. 
 
Humira is used to treat psoriatic arthritis in adults. Humira can slow down the damage to the joints caused 
by the disease and can help them move more freely. You may first be given other medicines. If you do not 
respond well enough to these medicines, you will be given Humira. 
 



452 

Plaque psoriasis  
 
Plaque psoriasis is a skin condition that causes red, flaky, crusty patches of skin covered with silvery 
scales. Plaque psoriasis can also affect the nails, causing them to crumble, become thickened and lift away 
from the nail bed which can be painful.   
 
Humira is used to treat 

 moderate to severe chronic plaque psoriasis in adults and  
 severe chronic plaque psoriasis in children and adolescents aged 4 to 17 years for whom topical 

therapy and phototherapies have either not worked very well or are not suitable. 
 

Hidradenitis suppurativa 
 
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic and often painful inflammatory skin 
disease. Symptoms may include tender nodules (lumps) and abscesses (boils) that may leak pus. It most 
commonly affects specific areas of the skin, such as under the breasts, the armpits, inner thighs, groin and 
buttocks. Scarring may also occur in affected areas. 
 
Humira is used to treat  

 moderate to severe hidradenitis suppurativa in adults and 
 moderate to severe hidradenitis suppurativa in adolescents aged 12 to 17 years.  

 
Humira can reduce the number of nodules and abscesses caused by the disease and the pain that is often 
associated with the disease. You may first be given other medicines. If you do not respond well enough to 
these medicines, you will be given Humira. 
 
Crohn’s disease 
 
Crohn’s disease is an inflammatory disease of the digestive tract. 
 
Humira is used to treat 

 moderate to severe Crohn’s disease in adults and  
 moderate to severe Crohn’s disease in children and adolescents aged 6 to 17 years 
 

You may first be given other medicines. If you do not respond well enough to these medicines, you will be 
given Humira. 

 
Ulcerative colitis 
 
Ulcerative colitis is an inflammatory disease of the large intestine. 
 
Humira is used to treat  

 moderate to severe ulcerative colitis in adults and  
 moderate to severe ulcerative colitis in children and adolescents aged 6 to 17 years 

 
You may first be given other medicines. If you do not respond well enough to these medicines, you will be 
given Humira. 
 
Non-infectious uveitis 
 
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. 
 
Humira is used to treat  



453 

 adults with non-infectious uveitis with inflammation affecting the back of the eye 
 children with chronic non-infectious uveitis from 2 years of age with inflammation affecting the 

front of the eye  
 
This inflammation may lead to a decrease of vision and/or the presence of floaters in the eye (black dots or 
wispy lines that move across the field of vision). Humira works by reducing this inflammation. 
 
You may first be given other medicines. If you do not respond well enough to these medicines, you will be 
given Humira. 
 
 
2. What you need to know before you use Humira 
 
Do not use Humira: 
 

 If you are allergic to adalimumab or any of the other ingredients of this medicine (listed in section 
6).  

 
 If you have active tuberculosis or other severe infections (see “Warnings and precautions”). It is 

important that you tell your doctor if you have symptoms of infections, for example, fever, 
wounds, feeling tired, dental problems. 

 
 If you have moderate or severe heart failure. It is important to tell your doctor if you have had or 

have a serious heart condition (see “Warnings and precautions”). 
 
Warnings and precautions 
 
Talk to your doctor or pharmacist before using Humira. 
 
Allergic reactions 
 

 If you get allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling 
or rash do not inject more Humira and contact your doctor immediately since, in rare cases, these 
reactions can be life threatening. 

 
Infections 
 

 If you have an infection, including long-term infection or an infection in one part of the body (for 
example, leg ulcer) consult your doctor before starting Humira. If you are unsure, contact your 
doctor.  

 
 You might get infections more easily while you are receiving Humira treatment. This risk may 

increase if you have problems with your lungs. These infections may be serious and include:  
 tuberculosis 
 infections caused by viruses, fungi, parasites or bacteria 
 severe infection in the blood (sepsis) 

 
In rare cases, these infections can be life-threatening. It is important to tell your doctor if you get 
symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may tell you to 
stop using Humira for some time. 
 



454 

 Tell your doctor if you live or travel in regions where fungal infections (for example, 
histoplasmosis, coccidioidomycosis or blastomycosis) are very common. 

 
 Tell your doctor if you have had infections which keep coming back or other conditions that 

increase the risk of infections. 
 

 If you are over 65 years you may be more likely to get infections while taking Humira. You and 
your doctor should pay special attention to signs of infection while you are being treated with 
Humira. It is important to tell your doctor if you get symptoms of infections, such as fever, 
wounds, feeling tired or dental problems. 

 
Tuberculosis 
 

 It is very important that you tell your doctor if you have ever had tuberculosis, or if you have been 
in close contact with someone who has had tuberculosis. If you have active tuberculosis, do not 
use Humira. 

 
 As cases of tuberculosis have been reported in patients treated with Humira, your doctor 

will check you for signs and symptoms of tuberculosis before starting Humira. This will 
include a thorough medical evaluation including your medical history and appropriate 
screening tests (for example, chest X-ray and a tuberculin test). The conduct and results of 
these tests should be recorded on your Patient Reminder Card.  

 Tuberculosis can develop during therapy even if you have received treatment for the 
prevention of tuberculosis.  

 If symptoms of tuberculosis (for example, cough that does not go away, weight loss, lack 
of energy, mild fever), or any other infection appear during or after therapy tell your 
doctor immediately. 
 

Hepatitis B 
 

 Tell your doctor if you are a carrier of the hepatitis B virus (HBV), if you have active HBV or if 
you think you might be at risk of getting HBV.  

 Your doctor should test you for HBV. In people who carry HBV, Humira can cause the 
virus to become active again. 

 In some rare cases, especially if you are taking other medicines that suppress the immune 
system, reactivation of HBV can be life-threatening.   

 
Surgery or dental procedure 
 

 If you are about to have surgery or dental procedures, please inform your doctor that you are 
taking Humira. Your doctor may recommend temporary discontinuation of Humira.  

 
Demyelinating disease 
 

 If you have or develop a demyelinating disease (a disease that affects the insulating layer around 
the nerves, such as multiple sclerosis), your doctor will decide if you should receive or continue to 
receive Humira. Tell your doctor immediately if you experience symptoms like changes in your 
vision, weakness in your arms or legs or numbness or tingling in any part of your body. 

 
Vaccinations 
 

 Certain vaccines may cause infections and should not be given while receiving Humira.  



455 

 
 Check with your doctor before you receive any vaccines.  
 It is recommended that children, if possible, be given all the scheduled vaccinations for 

their age before they start treatment with Humira. 
 If you received Humira while you were pregnant, your baby may be at higher risk for 

getting such an infection for up to approximately five months after the last Humira dose 
you received during pregnancy. It is important that you tell your baby's doctors and other 
health care professionals about your Humira use during your pregnancy so they can 
decide when your baby should receive any vaccine. 

 
Heart failure 
 

 If you have mild heart failure and are being treated with Humira, your heart failure status must be 
closely monitored by your doctor. It is important to tell your doctor if you have had or have a 
serious heart condition. If you develop new or worsening symptoms of heart failure (e.g. shortness 
of breath, or swelling of your feet), you must contact your doctor immediately. Your doctor will 
decide if you should receive Humira. 

 
Fever, bruising, bleeding or looking pale 
 

 In some patients the body may fail to produce enough of the blood cells that fight off 
infections or help you to stop bleeding. Your doctor may decide to stop treatment. If you 
develop a fever that does not go away, develop light bruises or bleed very easily or look very 
pale, call your doctor right away. 

 
Cancer 
 

 There have been very rare cases of certain kinds of cancer in children and adult patients taking 
Humira or other TNF blockers.   

 
 People with more serious rheumatoid arthritis that have had the disease for a long time 

may have a higher than average risk of getting lymphoma (a cancer that affects the lymph 
system) and leukaemia (a cancer that affects the blood and bone marrow).  

 If you take Humira the risk of getting lymphoma, leukaemia, or other cancers may 
increase. On rare occasions, an uncommon and severe type of lymphoma, has been seen in 
patients taking Humira. Some of those patients were also treated with azathioprine or 6-
mercaptopurine.  

 Tell your doctor if you are taking azathioprine or 6-mercaptopurine with Humira.  
 Cases of non-melanoma skin cancer have been observed in patients taking Humira.  
 If new skin lesions appear during or after therapy or if existing lesions change appearance, 

tell your doctor. 
 

 There have been cases of cancers, other than lymphoma in patients with a specific type of lung 
disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another TNF blocker. 
If you have COPD, or are a heavy smoker, you should discuss with your doctor whether treatment 
with a TNF blocker is appropriate for you. 

 
Autoimmune disease 
 

 On rare occasions, treatment with Humira could result in lupus-like syndrome. Contact your 
doctor if symptoms such as persistent unexplained rash, fever, joint pain or tiredness occur. 

 



456 

Children and adolescents 
 

 Vaccinations: if possible, children should be up to date with all vaccinations before using Humira. 
 

Other medicines and Humira 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 
 
You should not take Humira with medicines containing the following active substances due to increased 
risk of serious infection: 

 anakinra 
 abatacept. 

 
Humira can be taken together with: 

 methotrexate 
 certain disease-modifying anti-rheumatic agents (for example, sulfasalazine, hydroxychloroquine, 

leflunomide and injectable gold preparations) 
 steroids or pain medications including non-steroidal anti-inflammatory drugs (NSAIDs). 

 
If you have questions, please ask your doctor. 
 
Pregnancy and breast-feeding 
 

 You should consider the use of adequate contraception to prevent pregnancy and continue its use 
for at least 5 months after the last Humira treatment. 

 If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for 
advice about taking this medicine. 

 Humira should only be used during a pregnancy if needed. 
 According to a pregnancy study, there was no higher risk of birth defects when the mother had 

received Humira during pregnancy compared with mothers with the same disease who did not 
receive Humira. 

 Humira can be used during breast-feeding. 
 If you receive Humira during your pregnancy, your baby may have a higher risk for getting an 

infection. 
 It is important that you tell your baby’s doctors and other health care professionals about your 

Humira use during your pregnancy before the baby receives any vaccine. For more information on 
vaccines see the “Warnings and precautions” section. 

 
Driving and using machines 
 
Humira may have a small effect on your ability to drive, cycle or use machines. Room spinning sensation 
and vision disturbances may occur after taking Humira. 
 
 
3. How to use Humira 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are not sure.  
 
The recommended doses for Humira in each of the approved uses are shown in the following table.  
Your doctor may prescribe another strength of Humira if you need a different dose. 
 



457 

Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or axial spondyloarthritis 
without radiographic evidence of ankylosing spondylitis 
Age or body weight How much and how often to 

take?
Notes 

Adults  40 mg every other week In rheumatoid arthritis, 
methotrexate is continued while 
using Humira. If your doctor 
decides that methotrexate is 
inappropriate, Humira can be 
given alone. 
 
If you have rheumatoid arthritis 
and you do not receive 
methotrexate with your Humira 
therapy, your doctor may decide 
to give Humira 40 mg every 
week or 80 mg every other 
week. 

 
Polyarticular juvenile idiopathic arthritis
Age or body weight How much and how often to 

take?
Notes 

Children, adolescents and adults 
from 2 years of age weighing 30 
kg or more 

40 mg every other week Not applicable 

Children and adolescents from 2 
years of age weighing 10 kg to 
less than 30 kg 

20 mg every other week  Not applicable 

 
Enthesitis-related arthritis 
Age or body weight How much and how often to 

take?
Notes 

Children, adolescents and adults 
from 6 years of age weighing 30 
kg or more 

40 mg every other week  Not applicable 

Children and adolescents from 6 
years of age weighing 15 kg to 
less than 30 kg 

20 mg every other week Not applicable 

 
Plaque psoriasis 
Age or body weight How much and how often to 

take?
Notes 

Adults  
 

First dose of 80 mg (two 40 mg 
injections in one day), followed 
by 40 mg every other week 
starting one week after the first 
dose. 

If you have an inadequate 
response, your doctor may 
increase the dosage to 40 mg 
every week or 80 mg every 
other week. 

Children and adolescents from 4 
to 17 years of age weighing 30 
kg or more 

First dose of 40 mg, followed by 
40 mg one week later. 
 

Not applicable 



458 

Thereafter, the usual dose is 40 
mg every other week.

Children and adolescents from 4 
to 17 years of age weighing 15 
kg to less than 30 kg 

First dose of 20 mg, followed by 
20 mg one week later. 
 
Thereafter, the usual dose is 20 
mg every other week.

Not applicable 

 
Hidradenitis suppurativa 
Age or body weight How much and how often to 

take?
Notes 

Adults  First dose of 160 mg (four 40 
mg injections in one day or two 
40 mg injections per day for two 
consecutive days), followed by 
an 80 mg dose (two 40 mg 
injections in one day) two 
weeks later. After two further 
weeks, continue with a dose of 
40 mg every week or 80 mg 
every other week, as prescribed 
by your doctor.  

It is recommended that you use 
an antiseptic wash daily on the 
affected areas. 
 

Adolescents from 12 to 17 years 
of age weighing 30 kg or more 

First dose of 80 mg (two 40 mg 
injections in one day), followed 
by 40 mg every other week 
starting one week later.   

If you have an inadequate 
response to Humira 40 mg every 
other week, your doctor may 
increase the dosage to 40 mg 
every week or 80 mg every 
other week. 
It is recommended that you use 
an antiseptic wash daily on the 
affected areas. 

 
Crohn’s disease 
Age or body weight How much and how often to 

take?
Notes 

Children, adolescents and adults 
from 6 years of age weighing 40 
kg or more 

First dose of 80 mg (two 40 mg 
injections in one day), followed 
by 40 mg two weeks later. 
 
If a faster response is required, 
the doctor may prescribe a first 
dose of 160 mg (four 40 mg 
injections in one day or two 40 
mg injections per day for two 
consecutive days), followed by 
80 mg (two 40 mg injections in 
one day) two weeks later. 
 
Thereafter, the usual dose is 40 
mg every other week.

Your doctor may increase the 
dosage to 40 mg every week or 
80 mg every other week. 
 



459 

Children and adolescents from 6 
to 17 years of age weighing less 
than 40 kg 

First dose of 40 mg, followed by 
20 mg two weeks later.  
 
If a faster response is required, 
the doctor may prescribe a first 
dose of 80 mg (two 40 mg 
injections in one day), followed 
by 40 mg two weeks later. 
 
Thereafter, the usual dose is 20 
mg every other week.

Your doctor may increase the 
dose frequency to 20 mg every 
week. 
 

 
Ulcerative colitis 
Age or body weight How much and how often to 

take?
Notes 

Adults First dose of 160 mg (four 40 
mg injections in one day or two 
40 mg injections per day for two 
consecutive days), followed by 
80 mg (two 40 mg injections in 
one day) two weeks later. 
 
Thereafter, the usual dose is 
40 mg every other week.

Your doctor may increase the 
dosage to 40 mg every week or 
80 mg every other week. 

Children and adolescents from 6 
years of age weighing less than 
40 kg 

First dose of 80 mg (two 40 mg 
injections in one day), followed 
by 40 mg (one 40 mg injection) 
two weeks later. 
 
Thereafter, the usual dose is 40 
mg every other week.

You should continue taking 
Humira at your usual dose, even 
after turning 18 years of age. 

Children and adolescents from 6 
years of age weighing 40 kg or 
more 

First dose of 160 mg (four 40 
mg injections in one day or two 
40 mg injections per day for two 
consecutive days), followed by 
80 mg (two 40 mg injections in 
one day) two weeks later. 
 
Thereafter, the usual dose is 80 
mg every other week.

You should continue taking 
Humira at your usual dose, even 
after turning 18 years of age. 

 



460 

Non-infectious uveitis 
Age or body weight How much and how often to 

take?
Notes 

Adults First dose of 80 mg (two 40 mg 
injections in one day), followed 
by 40 mg every other week 
starting one week after the first 
dose.

Corticosteroids or other 
medicines that influence the 
immune system may be 
continued while using Humira. 
Humira can also be given alone.

Children and adolescents from 
2 years of age weighing less 
than 30 kg 
 

20 mg every other week Your doctor may prescribe an 
initial dose of 40 mg to be 
administered one week prior to 
the start of the usual dose of 
20 mg every other week. 
Humira is recommended for use 
in combination with 
methotrexate. 

Children and adolescents from 
2 years of age weighing at least 
30 kg 
 

40 mg every other week  Your doctor may prescribe an 
initial dose of 80 mg to be 
administered one week prior to 
the start of the usual dose of 
40 mg every other week. 
Humira is recommended for use 
in combination with 
methotrexate. 

 
Method and route of administration 
 
Humira is administered by injection under the skin (by subcutaneous injection). 
 
Detailed instructions on how to inject Humira are provided in section 7 ‘Injecting Humira’. 
 
If you use more Humira than you should 
 
If you accidentally inject Humira more frequently than told to by your doctor or pharmacist, call your 
doctor or pharmacist and tell them that you have taken more. Always take the outer carton of the medicine 
with you, even if it is empty.  
 
If you forget to use Humira 
 
If you forget to give yourself an injection, you should inject the next dose of Humira as soon as you 
remember. Then take your next dose as you would have on your originally scheduled day, had you not 
forgotten a dose.  
 
If you stop using Humira 
 
The decision to stop using Humira should be discussed with your doctor. Your symptoms may return if 
you stop using Humira. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 



461 

4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side 
effects are mild to moderate. However, some may be serious and require treatment. Side effects may occur 
at least up to 4 months after the last Humira injection.  
 
Tell your doctor immediately if you notice any of the following 
 
 severe rash, hives or other signs of allergic reaction  
 swollen face, hands, feet 
 trouble breathing, swallowing 
 shortness of breath with physical activity or upon lying down or swelling of the feet 

 
Tell your doctor as soon as possible if you notice any of the following 
 
 signs of infection such as fever, feeling sick, wounds, dental problems, burning on urination 
 feeling weak or tired 
 coughing 
 tingling 
 numbness 
 double vision 
 arm or leg weakness 
 a bump or open sore that doesn't heal 
 signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, 

paleness 
 
The symptoms described above can be signs of the below listed side effects, which have been observed 
with Humira. 
 
Very common (may affect more than 1 in 10 people)   
 
 injection site reactions (including pain, swelling, redness or itching) 
 respiratory tract infections (including cold, runny nose, sinus infection, pneumonia) 
 headache 
 abdominal pain 
 nausea and vomiting 
 rash 
 musculoskeletal pain 
 
Common (may affect up to 1 in 10 people)  
 
 serious infections (including blood poisoning and influenza) 
 intestinal infections (including gastroenteritis) 
 skin infections (including cellulitis and shingles) 
 ear infections 
 oral infections (including tooth infections and cold sores) 
 reproductive tract infections 
 urinary tract infection 
 fungal infections 
 joint infections 
 benign tumours 



462 

 skin cancer 
 allergic reactions (including seasonal allergy) 
 dehydration 
 mood swings (including depression) 
 anxiety 
 difficulty sleeping 
 sensation disorders such as tingling, prickling or numbness 
 migraine 
 nerve root compression (including low back pain and leg pain) 
 vision disturbances 
 eye inflammation 
 inflammation of the eye lid and eye swelling 
 vertigo (feeling of dizziness or spinning) 
 sensation of heart beating rapidly 
 high blood pressure 
 flushing 
 haematoma (collection of blood outside of blood vessels) 
 cough 
 asthma 
 shortness of breath 
 gastrointestinal bleeding 
 dyspepsia (indigestion, bloating, heart burn) 
 acid reflux disease 
 sicca syndrome (including dry eyes and dry mouth) 
 itching 
 itchy rash 
 bruising 
 inflammation of the skin (such as eczema) 
 breaking of finger nails and toe nails 
 increased sweating 
 hair loss 
 new onset or worsening of psoriasis 
 muscle spasms 
 blood in urine 
 kidney problems 
 chest pain 
 oedema (swelling) 
 fever 
 reduction in blood platelets which increases risk of bleeding or bruising 
 impaired healing 
 
Uncommon (may affect up to 1 in 100 people)   
 
 opportunistic infections (which include tuberculosis and other infections that occur when resistance 

to disease is lowered) 
 neurological infections (including viral meningitis) 
 eye infections 
 bacterial infections 
 diverticulitis (inflammation and infection of the large intestine) 
 cancer 



463 

 cancer that affects the lymph system 
 melanoma 
 immune disorders that could affect the lungs, skin and lymph nodes (most commonly presenting as 

sarcoidosis) 
 vasculitis (inflammation of blood vessels) 
 tremor (shaking) 
 neuropathy (disorder of the nerves) 
 stroke 
 hearing loss, buzzing 
 sensation of heart beating irregularly such as skipped beats 
 heart problems that can cause shortness of breath or ankle swelling 
 heart attack 
 a sac in the wall of a major artery, inflammation and clot of a vein, blockage of a blood vessel 
 lung diseases causing shortness of breath (including inflammation) 
 pulmonary embolism (blockage in an artery of the lung) 
 pleural effusion (abnormal collection of fluid in the pleural space) 
 inflammation of the pancreas which causes severe pain in the abdomen and back 
 difficulty in swallowing 
 facial oedema (swelling of the face) 
 gallbladder inflammation, gallbladder stones 
 fatty liver 
 night sweats 
 scar 
 abnormal muscle breakdown 
 systemic lupus erythematosus (including inflammation of skin, heart, lung, joints and other organ 

systems) 
 sleep interruptions 
 impotence 
 inflammations 
 
Rare (may affect up to 1 in 1,000 people) 
 
 leukaemia (cancer affecting the blood and bone marrow) 
 severe allergic reaction with shock 
 multiple sclerosis 
 nerve disorders (such as eye nerve inflammation and Guillain-Barré syndrome that may cause 

muscle weakness, abnormal sensations, tingling in the arms and upper body) 
 heart stops pumping 
 pulmonary fibrosis (scarring of the lung) 
 intestinal perforation (hole in the intestine) 
 hepatitis 
 reactivation of hepatitis B 
 autoimmune hepatitis (inflammation of the liver caused by the body's own immune system) 
 cutaneous vasculitis (inflammation of blood vessels in the skin) 
 Stevens-Johnson syndrome (early symptoms include malaise, fever, headache and rash) 
 facial oedema (swelling of the face) associated with allergic reactions 
 erythema multiforme (inflammatory skin rash) 
 lupus-like syndrome 
 angioedema (localized swelling of the skin) 
 lichenoid skin reaction (itchy reddish-purple skin rash) 



464 

 
Not known (frequency cannot be estimated from the available data) 
 
 hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal) 
 Merkel cell carcinoma (a type of skin cancer) 
 Kaposi’s sarcoma, a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma 

most commonly appears as purple lesions on the skin 
 liver failure 
 worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle         

weakness) 
 
Some side effects observed with Humira may not have symptoms and may only be discovered through 
blood tests. These include: 
 
Very common (may affect more than 1 in 10 people) 
 
 low blood measurements for white blood cells 
 low blood measurements for red blood cells 
 increased lipids in the blood 
 elevated liver enzymes 
 
Common (may affect up to 1 in 10 people) 
 
 high blood measurements for white blood cells 
 low blood measurements for platelets 
 increased uric acid in the blood 
 abnormal blood measurements for sodium 
 low blood measurements for calcium 
 low blood measurements for phosphate 
 high blood sugar 
 high blood measurements for lactate dehydrogenase 
 autoantibodies present in the blood 
 low blood potassium 
 
Uncommon (may affect up to 1 in 100 people)  
 
 elevated bilirubin measurement (liver blood test) 
 
Rare (may affect up to 1 in 1,000 people) 
 
 low blood measurements for white blood cells, red blood cells and platelet count 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V.  By reporting side effects, you can help provide more information on the safety of this 
medicine. 
 
 
5. How to store Humira 
 
Keep this medicine out of the sight and reach of children.  



465 

 
Do not use this medicine after the expiry date stated on the label/blister/carton after EXP.  
 
Store in a refrigerator (2C – 8C). Do not freeze.  
 
Keep the pre-filled pen in the outer carton in order to protect from light.   
 
Alternative Storage: 
 
When needed (for example, when you are travelling), a single Humira pre-filled pen may be stored at 
room temperature (up to 25°C) for a maximum period of 14 days – be sure to protect it from light. Once 
removed from the refrigerator for room temperature storage, the pen must be used within 14 days or 
discarded, even if it is returned to the refrigerator.   
 
You should record the date when the pen is first removed from refrigerator and the date after which it 
should be discarded. 
 
Do not throw away any medicines via wastewater or household waste. Ask your doctor or pharmacist how 
to throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Humira contains 
 
The active substance is adalimumab. 
The other ingredients are mannitol, polysorbate 80 and water for injections. 
 
What the Humira pre-filled pen looks like and contents of the pack 
 
Humira 40 mg solution for injection in pre-filled pen is supplied as a sterile solution of 40 mg adalimumab 
dissolved in 0.4 ml solution. 
 
The Humira pre-filled pen is a single-use grey and plum-coloured pen which contains a glass syringe with 
Humira. There are two caps – one is grey and labelled ‘1’ and the other is plum and labelled ‘2’. There is a 
window on each side of the pen through which you can see the Humira solution inside the syringe.   
 
The Humira pre-filled pen is available in packs containing 1, 2, 4 and 6 pre-filled pens. The 1 pre-filled 
pen pack comes with 2 alcohol pads (1 spare). For the 2, 4 and 6 pre-filled pen packs, each pre-filled pen 
comes with 1 alcohol pad.   
 
Not all pack sizes may be marketed.   
 
Humira may be available as a vial, a pre-filled syringe and/or a pre-filled pen. 
 
Marketing Authorisation Holder 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
Manufacturer  



466 

 
AbbVie Biotechnology GmbH 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
AbbVie SA 
Tél/Tel: +32 10  477811 

Lietuva 
AbbVie UAB  
Tel: +370 5 205 3023 

България 
АбВи ЕООД 
Тел.:+359 2 90 30 430 

Luxembourg/Luxemburg 
AbbVie SA 
Belgique/Belgien 
Tél/Tel: +32 10 477811

Česká republika 
AbbVie s.r.o.  
Tel: +420 233 098 111 

Magyarország 
AbbVie Kft. 
Tel.:+36 1 455 8600

Danmark 
AbbVie A/S 
Tlf: +45 72 30-20-28 

Malta 
V.J.Salomone Pharma Limited  
Tel: +356 22983201

Deutschland 
AbbVie Deutschland GmbH & Co. KG 
Tel: 00800 222843 33 (gebührenfrei) 
Tel: +49 (0) 611 / 1720-0

Nederland 
AbbVie B.V. 
Tel:  +31 (0)88 322 2843 

Eesti 
AbbVie Biopharmaceuticals GmbH Eesti filiaal  
Tel: +372 623 1011 

Norge 
AbbVie AS 
Tlf: +47 67 81 80 00

Ελλάδα 
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. 
Τηλ: +30 214 4165 555 

Österreich 
AbbVie GmbH  
Tel: +43 1 20589-0 

España 
AbbVie Spain, S.L.U. 
Tel:  +34 91 384 09 10 

Polska 
AbbVie Polska Sp. z o.o. 
Tel.: +48 22 372 78 00 

France 
AbbVie 
Tél: +33 (0) 1 45 60 13 00 

Portugal 
AbbVie, Lda.  
Tel: +351 (0)21 1908400

Hrvatska  
AbbVie d.o.o. 
Tel + 385 (0)1 5625 501

România 
AbbVie S.R.L. 
Tel: +40 21 529 30 35

Ireland 
AbbVie Limited  
Tel: +353 (0)1 4287900

Slovenija 
AbbVie Biofarmacevtska družba d.o.o. 
Tel: +386 (1)32 08 060

Ísland 
Vistor hf. 
Tel: +354 535 7000 

Slovenská republika 
AbbVie s.r.o. 
Tel: +421 2 5050 0777

Italia 
AbbVie S.r.l.  
Tel: +39 06 928921 

Suomi/Finland 
AbbVie Oy  
Puh/Tel:  +358 (0)10 2411 200 

Κύπρος 
Lifepharma (Z.A.M.) Ltd

Sverige 
AbbVie AB



467 

Τηλ.: +357 22 34 74 40 Tel:  +46 (0)8 684 44 600
Latvija 
AbbVie SIA  
Tel: +371 67605000 

United Kingdom 
AbbVie Ltd  
Tel: +44 (0)1628 561090

 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the 
local representative of the Marketing Authorisation Holder. 
 
 
7.  Injecting Humira 
 

 The following instructions explain how to give yourself a subcutaneous injection of Humira using 
the pre-filled pen. First read all the instructions carefully and then follow them step by step.  
 

 You will be instructed by your doctor, nurse or pharmacist on the technique of self-injection.  
 

 Do not attempt to self-inject until you are sure that you understand how to prepare and give the 
injection.  
 

 After proper training, the injection can be given by yourself or given by another person, for 
example, a family member or friend. 
 

 Only use each pre-filled pen for one injection. 
 
Humira Pre-filled Pen 
 
   Grey Cap 1     White Needle Sleeve      White Arrow                                    Plum-coloured Cap 2 

 
                              Needle           Inspection Window                    Plum Activator Button      
            
Do not use the pre-filled pen and call your doctor or pharmacist if the 
 

 liquid is cloudy, discoloured, or has flakes or particles in it 
 expiry (EXP) date has passed 
 liquid has been frozen or left in direct sunlight 
 pre-filled pen has been dropped or crushed 

 
Do not remove the caps until just before injection. Keep Humira out of the sight and reach of 
children. 
 



468 

STEP 1 
 
Take Humira out of the refrigerator. 
 
Leave Humira at room temperature for 15 to 30 minutes before injecting. 
 

 Do not remove the Grey or Plum-coloured Caps while allowing Humira to reach room 
temperature 

 Do not warm Humira in any other way. For example, do not warm it in a microwave or in hot 
water 

STEP 2  
 
               Pen 

 

                Pad 

 
Check expiry (EXP) date. Do not use the pre-filled pen if 
expiry (EXP) date has passed. 
 
Place the following on a clean, flat surface 
 

 1 single-use pre-filled pen and  
 1 alcohol pad 

 
Wash and dry your hands. 

STEP 3 
 
Injectable Areas 

     Injectable Areas 

 
Choose an injection site: 
 

 On the front of your thighs or 
 Your belly (abdomen) at least 5 cm from your belly 

button (navel) 
 At least 3 cm from your last injection site 

 
Wipe the injection site in a circular motion with the alcohol 
pad. 
 

 Do not inject through clothes 
 Do not inject into skin that is sore, bruised, red, 

hard, scarred, has stretch marks, or areas with 
psoriasis plaques 



469 

STEP 4 
 

 

 
Hold the pre-filled pen with the Grey Cap 1 pointing up.  
 
Check the inspection window. 
 

 It is normal to see 1 or more bubbles in the window 
 Make sure the liquid is clear and colourless 
 Do not use the pre-filled pen if the liquid is cloudy 

or has particles 
 Do not use the pre-filled pen if it has been dropped 

or crushed 

STEP 5  
 
 Cap 1 

 
                                            Cap 2 

 
Pull the Grey Cap 1 straight off. Throw the cap away. Do 
not recap. 
 

 Check that the small black needle cover of the 
syringe has been removed with the cap 

 It is normal to see a few drops of liquid come out of 
the needle 

 
Pull the Plum-coloured Cap 2 straight off. Throw the cap 
away. Do not recap. 
 
The pre-filled pen is now ready to use. 
 
Turn the pre-filled pen so that the white arrow points toward 
the injection site.

STEP 6 
 

 
Squeeze the skin at your injection site with your other hand 
to make a raised area and hold it firmly until the injection is 
complete. 
 
Point the white arrow toward the injection site (thigh or 
abdomen). 
 
Place the white needle sleeve straight (90˚ angle) against the 
injection site. 
 
Hold the pre-filled pen so that you can see the inspection 
window. 
 
Do not press the plum activator button until you are ready to 
inject. 



470 

STEP 7 
 
                             10 Seconds                  

 

 
Firmly push the pre-filled pen down against the injection 
site before starting the injection. 
Keep pushing down to prevent the pre-filled pen from 
moving away from the skin during the injection. 
 
Press the plum activator button and count slowly for 10 
seconds. 
 

 A loud “click” will signal the start of the injection 
 Keep pushing the pre-filled pen down firmly 

against the injection site until the injection is 
complete. 

 
The injection is complete when the yellow indicator has 
stopped moving. 

STEP 8 

  

 
When the injection is completed, slowly pull the pre-filled 
pen from the skin. The white needle sleeve will cover the 
needle tip. 

 A small amount of liquid on the injection site is 
normal 

 
If there are more than a few drops of liquid on the injection 
site, contact your doctor, nurse or pharmacist. 
 
After completing the injection, place a cotton ball or gauze 
pad on the skin over the injection site. 
 

 Do not rub 
 Slight bleeding at the injection site is normal 

STEP 9 
 
Throw away the used pre-filled pen in a special disposal container as instructed by your doctor, nurse 
or pharmacist. 
 

 Do not recycle or throw the pre-filled pen in the household waste 
 Always keep the pre-filled pen and the special disposal container out of the sight and reach of 

children 
 

The caps, alcohol pad, cotton ball or gauze pad, blister and packaging may be put in your household 
waste. 

 



471 

Package leaflet: Information for the patient 
 

Humira 80 mg solution for injection in pre-filled syringe 
adalimumab 

 
Read all of this leaflet carefully before you start using this medicine because it contains important 
information for you. 
 Keep this leaflet. You may need to read it again. 
 Your doctor will also give you a Patient Reminder Card, which contains important safety 

information that you need to be aware of before you begin using Humira and during treatment with 
Humira. Keep this Patient Reminder Card with you.  

 If you have any questions, ask your doctor or pharmacist. 
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even 

if their signs of illness are the same as yours. 
 If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Humira is and what it is used for 
2. What you need to know before you use Humira 
3. How to use Humira 
4. Possible side effects 
5. How to store Humira 
6. Contents of the pack and other information 
7. Injecting Humira 
 
 
1. What Humira is and what it is used for 
 
Humira contains the active substance adalimumab. 
 
Humira is used to treat 

 Rheumatoid arthritis 
 Plaque psoriasis 
 Hidradenitis suppurativa 
 Crohn’s disease 
 Ulcerative colitis 
 Non-infectious uveitis 

 
The active ingredient in Humira, adalimumab, is a human monoclonal antibody. Monoclonal antibodies 
are proteins that attach to a specific target. 
 
The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the 
immune (defence) system and is present at increased levels in the inflammatory diseases listed above. By 
attaching to TNFα, Humira decreases the process of inflammation in these diseases. 
 
Rheumatoid arthritis 
 
Rheumatoid arthritis is an inflammatory disease of the joints. 
 



472 

Humira is used to treat moderate to severe rheumatoid arthritis in adults. You may first be given other 
disease-modifying medicines, such as methotrexate. If you do not respond well enough to these medicines, 
you will be given Humira. 
 
Humira can also be used to treat severe, active and progressive rheumatoid arthritis without previous 
methotrexate treatment. 
 
Humira can slow down the damage to the joints caused by the inflammatory disease and can help them 
move more freely.  
 
Your doctor will decide if Humira should be used with methotrexate or alone. 
 
Plaque psoriasis  
 
Plaque psoriasis is a skin condition that causes red, flaky, crusty patches of skin covered with silvery 
scales. Plaque psoriasis can also affect the nails, causing them to crumble, become thickened and lift away 
from the nail bed which can be painful.   
 
Humira is used to treat moderate to severe chronic plaque psoriasis in adults.   
 
Hidradenitis suppurativa 
 
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic and often painful inflammatory skin 
disease. Symptoms may include tender nodules (lumps) and abscesses (boils) that may leak pus. It most 
commonly affects specific areas of the skin, such as under the breasts, the armpits, inner thighs, groin and 
buttocks. Scarring may also occur in affected areas. 
 
Humira is used to treat  

 moderate to severe hidradenitis suppurativa in adults and 
 moderate to severe hidradenitis suppurativa in adolescents aged 12to 17 years. 
 

Humira can reduce the number of nodules and abscesses caused by the disease and the pain that is often 
associated with the disease. You may first be given other medicines. If you do not respond well enough to 
these medicines, you will be given Humira. 
 
Crohn’s disease 
 
Crohn’s disease is an inflammatory disease of the digestive tract. 
 
Humira is used to treat  

 moderate to severe Crohn’s disease in adults and  
 moderate to severe Crohn’s disease in children and adolescents aged 6 to 17 years.  

 
You may first be given other medicines. If you do not respond well enough to these medicines, you will be 
given Humira. 
 
Ulcerative colitis 
 
Ulcerative colitis is an inflammatory disease of the large intestine. 
 
Humira is used to treat  

 moderate to severe ulcerative colitis in adults and  
 moderate to severe ulcerative colitis in children and adolescents aged 6 to 17 years 



473 

 
You may first be given other medicines. If you do not respond well enough to these medicines, you will be 
given Humira. 
 
Non-infectious uveitis 

 
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. 
 
Humira is used to treat  

 adults with non-infectious uveitis with inflammation affecting the back of the eye  
 children with chronic non-infectious uveitis from 2 years of age with inflammation affecting the 

front of the eye  
 

This inflammation may lead to a decrease of vision and/or the presence of floaters in the eye (black dots or 
wispy lines that move across the field of vision). Humira works by reducing this inflammation. You may 
first be given other medicines. If you do not respond well enough to these medicines, you will be given 
Humira. 
 
 
2. What you need to know before you use Humira 
 
Do not use Humira: 
 

 If you are allergic to adalimumab or any of the other ingredients of this medicine (listed in section 
6).  

 
 If you have active tuberculosis or other severe infections (see “Warnings and precautions”). It is 

important that you tell your doctor if you have symptoms of infections, for example, fever, 
wounds, feeling tired, dental problems. 

 
 If you have moderate or severe heart failure. It is important to tell your doctor if you have had or 

have a serious heart condition (see “Warnings and precautions”). 
 
Warnings and precautions 
  
Talk to your doctor or pharmacist before using Humira. 
 
Allergic reactions 
 

 If you get allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling 
or rash do not inject more Humira and contact your doctor immediately since, in rare cases, these 
reactions can be life threatening.  

 
Infections 
 

 If you have an infection, including long-term infection or an infection in one part of the body (for 
example, leg ulcer) consult your doctor before starting Humira. If you are unsure, contact your 
doctor.  

 
 You might get infections more easily while you are receiving Humira treatment. This risk may 

increase if you have problems with your lungs. These infections may be serious and include: 
 tuberculosis 



474 

 infections caused by viruses, fungi, parasites or bacteria 
 severe infection in the blood (sepsis) 

 
In rare cases, these infections can be life-threatening. It is important to tell your doctor if you get 
symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may tell you to 
stop using Humira for some time. 

 
 Tell your doctor if you live or travel in regions where fungal infections (for example, 

histoplasmosis, coccidioidomycosis or blastomycosis) are very common. 
 

 Tell your doctor if you have had infections which keep coming back or other conditions that 
increase the risk of infections. 

 
 If you are over 65 years you may be more likely to get infections while taking Humira. You and 

your doctor should pay special attention to signs of infection while you are being treated with 
Humira. It is important to tell your doctor if you get symptoms of infections, such as fever, 
wounds, feeling tired or dental problems. 

 
Tuberculosis 
 

 It is very important that you tell your doctor if you have ever had tuberculosis, or if you have been 
in close contact with someone who has had tuberculosis. If you have active tuberculosis, do not 
use Humira. 

 
 As cases of tuberculosis have been reported in patients treated with Humira, your doctor 

will check you for signs and symptoms of tuberculosis before starting Humira. This will 
include a thorough medical evaluation including your medical history and appropriate 
screening tests (for example, chest X-ray and a tuberculin test). The conduct and results of 
these tests should be recorded on your Patient Reminder Card.   

 Tuberculosis can develop during therapy even if you have received treatment for the 
prevention of tuberculosis.  

 If symptoms of tuberculosis (for example, cough that does not go away, weight loss, lack 
of energy, mild fever), or any other infection appear during or after therapy tell your 
doctor immediately.  

 
Hepatitis B 
 

 Tell your doctor if you are a carrier of the hepatitis B virus (HBV), if you have active HBV or if 
you think you might be at risk of getting HBV.   

 
 Your doctor should test you for HBV. In people who carry HBV, Humira can cause the 

virus to become active again.  
 In some rare cases, especially if you are taking other medicines that suppress the immune 

system, reactivation of HBV can be life-threatening.  
 
Surgery or dental procedure 
 

 If you are about to have surgery or dental procedures, please inform your doctor that you are 
taking Humira. Your doctor may recommend temporary discontinuation of Humira. 

 
Demyelinating disease 
 



475 

 If you have or develop a demyelinating disease (a disease that affects the insulating layer around 
the nerves, such as multiple sclerosis), your doctor will decide if you should receive or continue to 
receive Humira. Tell your doctor immediately if you experience symptoms like changes in your 
vision, weakness in your arms or legs or numbness or tingling in any part of your body. 

 
Vaccinations 
 

 Certain vaccines may cause infections and should not be given while receiving Humira.   
 

 Check with your doctor before you receive any vaccines.  
 It is recommended that children, if possible, be given all the scheduled vaccinations for 

their age before they start treatment with Humira.  
 If you received Humira while you were pregnant, your baby may be at higher risk for 

getting such an infection for up to approximately five months after the last Humira dose 
you received during pregnancy. It is important that you tell your baby's doctors and other 
health care professionals about your Humira use during your pregnancy so they can 
decide when your baby should receive any vaccine. 

 
Heart failure 
 

 If you have mild heart failure and are being treated with Humira, your heart failure status must be 
closely monitored by your doctor. It is important to tell your doctor if you have had or have a 
serious heart condition. If you develop new or worsening symptoms of heart failure (e.g. shortness 
of breath, or swelling of your feet), you must contact your doctor immediately. Your doctor will 
decide if you should receive Humira. 

 
Fever, bruising, bleeding or looking pale 
 

 In some patients the body may fail to produce enough of the blood cells that fight off infections or 
help you to stop bleeding. Your doctor may decide to stop treatment. If you develop a fever that 
does not go away, develop light bruises or bleed very easily or look very pale, call your doctor 
right away. 

 
Cancer 
 

 There have been very rare cases of certain kinds of cancer in children and adult patients taking 
Humira or other TNF blockers.  

 
 People with more serious rheumatoid arthritis that have had the disease for a long time 

may have a higher than average risk of getting lymphoma (a cancer that affects the lymph 
system) and leukaemia (a cancer that affects the blood and bone marrow).  

 If you take Humira the risk of getting lymphoma, leukaemia, or other cancers may 
increase. On rare occasions, an uncommon and severe type of lymphoma has been seen in 
patients taking Humira. Some of those patients were also treated with azathioprine or 6- 
mercaptopurine.  

 Tell your doctor if you are taking azathioprine or 6-mercaptopurine with Humira.  
 Cases of non-melanoma skin cancer have been observed in patients taking Humira.  
 If new skin lesions appear during or after therapy or if existing lesions change appearance, 

tell your doctor. 
 

 There have been cases of cancers, other than lymphoma in patients with a specific type of lung 
disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another TNF blocker. 



476 

If you have COPD, or are a heavy smoker, you should discuss with your doctor whether treatment 
with a TNF blocker is appropriate for you. 

 
Autoimmune disease 
 

 On rare occasions, treatment with Humira could result in lupus-like syndrome. Contact your 
doctor if symptoms such as persistent unexplained rash, fever, joint pain or tiredness occur. 

 
Children and adolescents 
 

 Vaccinations: if possible, children should be up to date with all vaccinations before using Humira. 
 

Other medicines and Humira 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 
 
You should not take Humira with medicines containing the following active substances due to increased 
risk of serious infection: 

 anakinra 
 abatacept. 

 
Humira can be taken together with: 

 methotrexate  
 certain disease-modifying anti-rheumatic agents (for example, sulfasalazine, hydroxychloroquine, 

leflunomide and injectable gold preparations) 
 steroids or pain medications including non-steroidal anti-inflammatory drugs (NSAIDs). 

 
If you have questions, please ask your doctor.  
 
Pregnancy and breast-feeding 
 

 You should consider the use of adequate contraception to prevent pregnancy and continue its use 
for at least 5 months after the last Humira treatment. 

 If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for 
advice about taking this medicine. 

 Humira should only be used during a pregnancy if needed. 
 According to a pregnancy study, there was no higher risk of birth defects when the mother had 

received Humira during pregnancy compared with mothers with the same disease who did not 
receive Humira. 

 Humira can be used during breast-feeding. 
 If you receive Humira during your pregnancy, your baby may have a higher risk for getting an 

infection. 
 It is important that you tell your baby’s doctors and other health care professionals about your 

Humira use during your pregnancy before the baby receives any vaccine.  For more information 
on vaccines see the “Warnings and precautions” section. 

 
Driving and using machines 
 
Humira may have a small effect on your ability to drive, cycle or use machines. Room spinning sensation 
and vision disturbances may occur after taking Humira. 
 



477 

 
3. How to use Humira 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are not sure.  
 
The recommended doses for Humira in each of the approved uses are shown in the following table. Your 
doctor may prescribe another strength of Humira if you need a different dose. 
 

Rheumatoid arthritis 
Age or body weight How much and how often to 

take?
Notes 

Adults  40 mg every other week In rheumatoid arthritis, 
methotrexate is continued while 
using Humira. If your doctor 
decides that methotrexate is 
inappropriate, Humira can be 
given alone. 
 
If you have rheumatoid arthritis 
and you do not receive 
methotrexate with your Humira 
therapy, your doctor may decide 
to give Humira 40 mg every 
week or 80 mg every other 
week. 

 
Plaque psoriasis 
Age or body weight How much and how often to 

take?
Notes 

Adults 
 

First dose of 80 mg (one 80 mg 
injection), followed by 40 mg 
every other week starting one 
week after the first dose. 

If you have an inadequate 
response, your doctor may 
increase the dosage to 40 mg 
every week or 80 mg every 
other week. 

 



478 

Hidradenitis suppurativa 
Age or body weight How much and how often to 

take?
Notes 

Adults First dose of 160 mg (two 
80 mg injections in one day or 
one 80 mg injection per day for 
two consecutive days), followed 
by an 80 mg dose (one 80 mg 
injection) two weeks later. After 
two further weeks, continue 
with a dose of 40 mg every 
week or 80 mg every other 
week, as prescribed by your 
doctor.  

It is recommended that you use 
an antiseptic wash daily on the 
affected areas. 
 

Adolescents from 12 to 17 years 
of age weighing 30 kg or more 

First dose of 80 mg (one 80 mg 
injection), followed by 40 mg 
every other week starting one 
week later.   

If you have an inadequate 
response to Humira 40 mg every 
other week, your doctor may 
increase the dosage to 40 mg 
every week or 80 mg every 
other week.  
 
It is recommended that you use 
an antiseptic wash daily on the 
affected areas. 

 
Crohn’s disease 
Age or body weight How much and how often to 

take?
Notes 

Children, adolescents and adults 
from 6 years of age weighing 40 
kg or more 

First dose of 80 mg (one 80 mg 
injection), followed by 40 mg 
two weeks later. 
 
If a faster response is required, 
the doctor may prescribe a first 
dose of 160 mg (two 80 mg 
injections in one day or one 
80 mg injection per day for two 
consecutive days), followed by 
80 mg (one 80 mg injection) 
two weeks later. 
 
Thereafter, the usual dose is 
40 mg every other week.

Your doctor may increase the 
dosage to 40 mg every week or 
80 mg every other week. 
 



479 

Children and adolescents from 6 
to 17 years of age weighing less 
than 40 kg 

First dose of 40 mg, followed by 
20 mg two weeks later.  
 
If a faster response is required, 
the doctor may prescribe a first 
dose of 80 mg (one 80 mg 
injection), followed by 40 mg 
two weeks later. 
 
Thereafter, the usual dose is 
20 mg every other week.

Your doctor may increase the 
dose frequency to 20 mg every 
week. 
 

 
Ulcerative colitis 
Age or body weight How much and how often to 

take?
Notes 

Adults First dose of 160 mg (two 
80 mg injections in one day or 
one 80 mg injection per day for 
two consecutive days), followed 
by 80 mg (one 80 mg injection) 
two weeks later. 
 
Thereafter, the usual dose is 
40 mg every other week.

Your doctor may increase the 
dosage to 40 mg every week or 
80 mg every other week. 

Children and adolescents from 6 
years of age weighing less than 
40 kg 

First dose of 80 mg (one 80 mg 
injection), followed by 40 mg 
(one 40 mg injection) two 
weeks later. 
 
Thereafter, the usual dose is 40 
mg every other week.

You should continue taking 
Humira at your usual dose, even 
after turning 18 years of age. 

Children and adolescents from 6 
years of age weighing 40 kg or 
more 

First dose of 160 mg (two 80 
mg injections in one day or one 
80 mg injection per day for two 
consecutive days), followed by 
80 mg (one 80 mg injection) 
two weeks later. 
 
Thereafter, the usual dose is 80 
mg every other week.

You should continue taking 
Humira at your usual dose, even 
after turning 18 years of age. 

 
Non-infectious uveitis 
Age or body weight How much and how often to 

take?
Notes 

Adults First dose of 80 mg (one 80 mg 
injection), followed by 40 mg 
every other week starting one 
week after the first dose. 

Corticosteroids or other 
medicines that influence the 
immune system may be 
continued while using Humira. 
Humira can also be given alone.

Children and adolescents from 
2 years of age weighing less 
than 30 kg 
 

20 mg every other week Your doctor may prescribe an 
initial dose of 40 mg to be 
administered one week prior to 
the start of the usual dose of 



480 

20 mg every other week. 
Humira is recommended for use 
in combination with 
methotrexate. 

Children and adolescents from 
2 years of age weighing 30 kg 
or more 
 

40 mg every other week  Your doctor may prescribe an 
initial dose of 80 mg to be 
administered one week prior to 
the start of the usual dose of 
40 mg every other week. 
Humira is recommended for use 
in combination with 
methotrexate. 

 
Method and route of administration 
 
Humira is administered by injection under the skin (by subcutaneous injection). 
 
Detailed instructions on how to inject Humira are provided in section 7 ‘Injecting Humira’. 
 
If you use more Humira than you should 
 
If you accidentally inject Humira more frequently than told to by your doctor or pharmacist, call your 
doctor or pharmacist and tell them that you have taken more. Always take the outer carton of the medicine 
with you, even if it is empty.  
 
If you forget to use Humira 
 
If you forget to give yourself an injection, you should inject the next dose of Humira as soon as you 
remember. Then take your next dose as you would have on your originally scheduled day, had you not 
forgotten a dose.  
 
If you stop using Humira 
 
The decision to stop using Humira should be discussed with your doctor. Your symptoms may return if 
you stop using Humira. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side 
effects are mild to moderate. However, some may be serious and require treatment. Side effects may occur 
at least up to 4 months after the last Humira injection.   
 
Tell your doctor immediately if you notice any of the following 
 
 severe rash, hives or other signs of allergic reaction 
 swollen face, hands, feet 
 trouble breathing, swallowing 
 shortness of breath with physical activity or upon lying down or swelling of the feet 
 



481 

Tell your doctor as soon as possible if you notice any of the following 
 
 signs of infection such as fever, feeling sick, wounds, dental problems, burning on urination 
 feeling weak or tired 
 coughing 
 tingling 
 numbness 
 double vision 
 arm or leg weakness 
 a bump or open sore that doesn't heal 
 signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, 

paleness 
 
The symptoms described above can be signs of the below listed side effects, which have been observed 
with Humira. 
 
Very common (may affect more than 1 in 10 people)  
 
 injection site reactions (including pain, swelling, redness or itching) 
 respiratory tract infections (including cold, runny nose, sinus infection, pneumonia) 
 headache 
 abdominal pain 
 nausea and vomiting 
 rash 
 musculoskeletal pain 
 
Common (may affect up to 1 in 10 people) 
 
 serious infections (including blood poisoning and influenza) 
 intestinal infections (including gastroenteritis) 
 skin infections (including cellulitis and shingles) 
 ear infections 
 oral infections (including tooth infections and cold sores) 
 reproductive tract infections 
 urinary tract infection 
 fungal infections 
 joint infections 
 benign tumours 
 skin cancer 
 allergic reactions (including seasonal allergy) 
 dehydration 
 mood swings (including depression) 
 anxiety 
 difficulty sleeping 
 sensation disorders such as tingling, prickling or numbness 
 migraine 
 nerve root compression (including low back pain and leg pain) 
 vision disturbances 
 eye inflammation 
 inflammation of the eye lid and eye swelling 
 vertigo (feeling of dizziness or spinning) 



482 

 sensation of heart beating rapidly 
 high blood pressure 
 flushing 
 haematoma (collection of blood outside of blood vessels) 
 cough 
 asthma 
 shortness of breath 
 gastrointestinal bleeding 
 dyspepsia (indigestion, bloating, heart burn) 
 acid reflux disease 
 sicca syndrome (including dry eyes and dry mouth) 
 itching 
 itchy rash 
 bruising 
 inflammation of the skin (such as eczema) 
 breaking of finger nails and toe nails 
 increased sweating 
 hair loss 
 new onset or worsening of psoriasis 
 muscle spasms 
 blood in urine 
 kidney problems 
 chest pain 
 oedema (swelling) 
 fever 
 reduction in blood platelets which increases risk of bleeding or bruising 
 impaired healing 
 
Uncommon (may affect up to 1 in 100 people) 
 
 opportunistic infections (which include tuberculosis and other infections that occur when resistance 

to disease is lowered) 
 neurological infections (including viral meningitis) 
 eye infections 
 bacterial infections 
 diverticulitis (inflammation and infection of the large intestine) 
 cancer 
 cancer that affects the lymph system 
 melanoma 
 immune disorders that could affect the lungs, skin and lymph nodes (most commonly presenting as 

sarcoidosis) 
 vasculitis (inflammation of blood vessels) 
 tremor (shaking) 
 neuropathy (disorder of the nerves) 
 stroke 
 hearing loss, buzzing 
 sensation of heart beating irregularly such as skipped beats 
 heart problems that can cause shortness of breath or ankle swelling 
 heart attack 
 a sac in the wall of a major artery, inflammation and clot of a vein; blockage of a blood vessel 



483 

 lung diseases causing shortness of breath (including inflammation) 
 pulmonary embolism (blockage in an artery of the lung) 
 pleural effusion (abnormal collection of fluid in the pleural space) 
 inflammation of the pancreas which causes severe pain in the abdomen and back 
 difficulty in swallowing 
 facial oedema (swelling of the face) 
 gallbladder inflammation, gallbladder stones 
 fatty liver 
 night sweats 
 scar 
 abnormal muscle breakdown 
 systemic lupus erythematosus (including inflammation of skin, heart, lung, joints and other organ 

systems) 
 sleep interruptions 
 impotence 
 inflammations 
 
Rare (may affect up to 1 in 1,000 people) 
 
 leukaemia (cancer affecting the blood and bone marrow) 
 severe allergic reaction with shock 
 multiple sclerosis 
 nerve disorders (such as eye nerve inflammation and Guillain-Barré syndrome that may cause 

muscle weakness, abnormal sensations, tingling in the arms and upper body) 
 heart stops pumping 
 pulmonary fibrosis (scarring of the lung) 
 intestinal perforation (hole in the intestine) 
 hepatitis 
 reactivation of hepatitis B 
 autoimmune hepatitis (inflammation of the liver caused by the body's own immune system) 
 cutaneous vasculitis (inflammation of blood vessels in the skin) 
 Stevens-Johnson syndrome (early symptoms include malaise, fever, headache and rash) 
 facial oedema (swelling of the face) associated with allergic reactions 
 erythema multiforme (inflammatory skin rash) 
 lupus-like syndrome 
 angioedema (localized swelling of the skin) 
 lichenoid skin reaction (itchy reddish-purple skin rash) 
 
Not known (frequency cannot be estimated from the available data) 
 
 hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal) 
 Merkel cell carcinoma (a type of skin cancer) 
 Kaposi’s sarcoma, a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma 

most commonly appears as purple lesions on the skin 
 liver failure 
 worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle         

weakness) 
 
Some side effects observed with Humira may not have symptoms and may only be discovered through 
blood tests. These include: 
 



484 

Very common (may affect more than 1 in 10 people)  
 
 low blood measurements for white blood cells 
 low blood measurements for red blood cells 
 increased lipids in the blood 
 elevated liver enzymes 
 
Common (may affect up to 1 in 10 people) 
 
 high blood measurements for white blood cells   
 low blood measurements for platelets 
 increased uric acid in the blood 
 abnormal blood measurements for sodium 
 low blood measurements for calcium 
 low blood measurements for phosphate 
 high blood sugar 
 high blood measurements for lactate dehydrogenase 
 autoantibodies present in the blood 
 low blood potassium 
 
Uncommon (may affect up to 1 in 100 people)  
 
 elevated bilirubin measurement (liver blood test) 
 
Rare (may affect up to 1 in 1,000 people) 
 
 low blood measurements for white blood cells, red blood cells and platelet count 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects, you can help provide more information on the safety of this 
medicine. 
 
 
5. How to store Humira 
 
Keep this medicine out of the sight and reach of children.  
 
Do not use this medicine after the expiry date stated on the label/blister/carton after EXP.  
 
Store in a refrigerator (2C – 8C). Do not freeze.  
 
Keep the pre-filled syringe in the outer carton in order to protect from light. 
 
Alternative Storage: 
 
When needed (for example when you are travelling), a single Humira pre-filled syringe may be stored at 
room temperature (up to 25°C) for a maximum period of 14 days – be sure to protect it from light. Once 
removed from the refrigerator for room temperature storage, the syringe must be used within 14 days or 
discarded, even if it is returned to the refrigerator.   
 



485 

You should record the date when the syringe is first removed from refrigerator and the date after which it 
should be discarded.   
 
Do not throw away any medicines via wastewater or household waste. Ask your doctor or pharmacist how 
to throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Humira contains 
 
The active substance is adalimumab. 
The other ingredients are mannitol, polysorbate 80 and water for injections. 
 
What the Humira pre-filled syringe looks like and contents of the pack 
 
Humira 80 mg solution for injection in pre-filled syringe is supplied as a sterile solution of 80 mg 
adalimumab dissolved in 0.8 ml solution. 
 
The Humira pre-filled syringe is a glass syringe containing a solution of adalimumab.  
 
The Humira pre-filled syringe is available in a pack containing 1 pre-filled syringe for patient use with 1 
alcohol pad.   
 
Humira may be available as a vial, a pre-filled syringe and/or a pre-filled pen. 
 
Marketing Authorisation Holder 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
Manufacturer  
 
AbbVie Biotechnology GmbH 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
AbbVie SA 
Tél/Tel: +32 10  477811 

Lietuva 
AbbVie UAB  
Tel: +370 5 205 3023 

България 
АбВи ЕООД 
Тел.:+359 2 90 30 430 

Luxembourg/Luxemburg 
AbbVie SA 
Belgique/Belgien 
Tél/Tel: +32 10 477811

Česká republika 
AbbVie s.r.o.  
Tel: +420 233 098 111 

Magyarország 
AbbVie Kft. 
Tel.:+36 1 455 8600



486 

Danmark 
AbbVie A/S 
Tlf: +45 72 30-20-28 

Malta 
V.J.Salomone Pharma Limited  
Tel: +356 22983201

Deutschland 
AbbVie Deutschland GmbH & Co. KG 
Tel: 00800 222843 33 (gebührenfrei) 
Tel: +49 (0) 611 / 1720-0

Nederland 
AbbVie B.V. 
Tel:  +31 (0)88 322 2843 

Eesti 
AbbVie Biopharmaceuticals GmbH Eesti filiaal  
Tel: +372 623 1011 

Norge 
AbbVie AS 
Tlf: +47 67 81 80 00

Ελλάδα 
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. 
Τηλ: +30 214 4165 555

Österreich 
AbbVie GmbH  
Tel: +43 1 20589-0

España 
AbbVie Spain, S.L.U. 
Tel:  +34 91 384 09 10 

Polska 
AbbVie Polska Sp. z o.o. 
Tel.: +48 22 372 78 00 

France 
AbbVie 
Tél: +33 (0) 1 45 60 13 00 

Portugal 
AbbVie, Lda.  
Tel: +351 (0)21 1908400 

Hrvatska  
AbbVie d.o.o. 
Tel + 385 (0)1 5625 501

România 
AbbVie S.R.L. 
Tel: +40 21 529 30 35

Ireland 
AbbVie Limited  
Tel: +353 (0)1 4287900

Slovenija 
AbbVie Biofarmacevtska družba d.o.o. 
Tel: +386 (1)32 08 060

Ísland 
Vistor hf. 
Tel: +354 535 7000 

Slovenská republika 
AbbVie s.r.o. 
Tel: +421 2 5050 0777

Italia 
AbbVie S.r.l.  
Tel: +39 06 928921 

Suomi/Finland 
AbbVie Oy  
Puh/Tel:  +358 (0)10 2411 200 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Τηλ.: +357 22 34 74 40

Sverige 
AbbVie AB 
Tel:  +46 (0)8 684 44 600

Latvija 
AbbVie SIA  
Tel: +371 67605000 

United Kingdom 
AbbVie Ltd  
Tel: +44 (0)1628 561090

 
This leaflet was last revised in  
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the 
local representative of the Marketing Authorisation Holder. 
 
 
7. Injecting Humira  
 

 The following instructions explain how to give yourself a subcutaneous injection of Humira using 
the pre-filled syringe. First read all the instructions carefully and then follow them step by step.  
 



487 

 You will be instructed by your doctor, nurse or pharmacist on the technique of self-injection.  
 

 Do not attempt to self-inject until you are sure that you understand how to prepare and give the 
injection.  
 

 After proper training, the injection can be given by yourself or given by another person, for 
example, a family member or friend.   
 

 Only use each pre-filled syringe for one injection. 
 
Humira Pre-filled Syringe 
 
          Plunger              Finger Grip          Needle Cover 

 
 

Do not use the pre-filled syringe and call your doctor or pharmacist if the 

 liquid is cloudy, discoloured, or has flakes or particles in it 
 expiry (EXP) date has passed 
 liquid has been frozen or left in direct sunlight 
 pre-filled syringe has been dropped or crushed 

 
Do not remove the needle cover until just before injection. Keep Humira out of the sight and reach 
of children. 
 

STEP 1 
 
Take Humira out of the refrigerator. 
 
Leave Humira at room temperature for 15 to 30 minutes before injecting. 
 

 Do not remove the needle cover while allowing Humira to reach room temperature 
 Do not warm Humira in any other way. For example, do not warm it in a microwave or in hot 

water 



488 

STEP 2  

           Syringe 

 
                 Pad 

Check the expiry (EXP) date. Do not use the pre-filled 
syringe if expiry (EXP) date has passed. 
 
Place the following on a clean, flat surface 
 

 1 single-use pre-filled syringe and  
 1 alcohol pad 

 
Wash and dry your hands. 

STEP 3 
 
Injectable Areas 

     Injectable Areas 

Choose an injection site: 
 

 On the front of your thighs or 
 Your belly (abdomen) at least 5 cm from your belly 

button (navel) 
 At least 3 cm from your last injection site 

 
Wipe the injection site in a circular motion with the alcohol 
pad. 
 

 Do not inject through clothes 
 Do not inject into skin that is sore, bruised, red, 

hard, scarred, has stretch marks, or areas with 
psoriasis plaques 

 
 



489 

STEP 4 

 

Hold the pre-filled syringe in one hand. 
 
Check the liquid in the pre-filled syringe. 
 

 Make sure the liquid is clear and colourless 
 Do not use the pre-filled syringe if the liquid is 

cloudy or has particles 
 Do not use the pre-filled syringe if it has been 

dropped or crushed 
 

Gently pull the needle cover straight off with the other hand. 
Throw the needle cover away. Do not recap. 
 

 Do not touch the needle with your fingers or let the 
needle touch anything 

STEP 5 

 

Hold the pre-filled syringe with the needle facing up. 
 

 Hold the pre-filled syringe at eye level with one 
hand so you can see the air in the pre-filled syringe 

 
Slowly push the plunger in to push the air out through the 
needle.  
 

 It is normal to see a drop of liquid at the end of the 
needle 

 

STEP 6 Hold the body of the pre-filled syringe in one hand between 
the thumb and index fingers, like you would a pencil. 
 
Squeeze the skin at your injection site with your other hand 
to make a raised area and hold it firmly. 

 



490 

STEP 7 

 

Insert the needle all the way into the skin at about a 45-
degree angle with one quick, short motion. 
 

 After the needle is in, let go of the skin you are 
holding  

 
Slowly push the plunger all the way in until all of the liquid 
is injected and the pre-filled syringe is empty. 
 

STEP 8 

 
             Cotton Ball 

When the injection is completed, slowly pull the needle out 
of the skin while keeping the pre-filled syringe at the same 
angle. 
 
After completing the injection, place a cotton ball or gauze 
pad on the skin over the injection site. 
 

 Do not rub 
 Slight bleeding at the injection site is normal 

 

 
STEP 9 
 
Throw away the used pre-filled syringe in a special disposal container as instructed by your doctor, 
nurse or pharmacist. Never recap a needle. 
 

 Do not recycle or throw the pre-filled syringe in the household waste 
 Always keep the pre-filled syringe and the special disposal container out of the sight and 

reach of children 
 

The needle cover, alcohol pad, cotton ball or gauze pad, blister and packaging may be put in your 
household waste. 

 

  



491 

Package leaflet: Information for the patient 
 

Humira 80 mg solution for injection in pre-filled syringe 
adalimumab 

 
Read all of this leaflet carefully before you start using this medicine because it contains important 
information for you. 
 Keep this leaflet. You may need to read it again. 
 Your doctor will also give you a Patient Reminder Card, which contains important safety 

information that you need to be aware of before you begin using Humira and during treatment with 
Humira. Keep this Patient Reminder Card with you.  

 If you have any questions, ask your doctor or pharmacist. 
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even 

if their signs of illness are the same as yours. 
 If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Humira is and what it is used for 
2. What you need to know before you use Humira 
3. How to use Humira 
4. Possible side effects 
5. How to store Humira 
6. Contents of the pack and other information 
7. Injecting Humira 
 
 
1. What Humira is and what it is used for 
 
Humira contains the active substance adalimumab. 
 
Humira is used to treat 

 Rheumatoid arthritis 
 Plaque psoriasis 
 Hidradenitis suppurativa 
 Crohn’s disease 
 Ulcerative colitis 
 Non-infectious uveitis 

 
The active ingredient in Humira, adalimumab, is a human monoclonal antibody. Monoclonal antibodies 
are proteins that attach to a specific target. 
 
The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the 
immune (defence) system and is present at increased levels in the inflammatory diseases listed above. By 
attaching to TNFα, Humira decreases the process of inflammation in these diseases. 
 
Rheumatoid arthritis 
 
Rheumatoid arthritis is an inflammatory disease of the joints. 
 



492 

Humira is used to treat moderate to severe rheumatoid arthritis in adults. You may first be given other 
disease-modifying medicines, such as methotrexate. If you do not respond well enough to these medicines, 
you will be given Humira. 
 
Humira can also be used to treat severe, active and progressive rheumatoid arthritis without previous 
methotrexate treatment. 
 
Humira can slow down the damage to the joints caused by the inflammatory disease and can help them 
move more freely.  
 
Your doctor will decide if Humira should be used with methotrexate or alone. 
 
Plaque psoriasis  
 
Plaque psoriasis is a skin condition that causes red, flaky, crusty patches of skin covered with silvery 
scales. Plaque psoriasis can also affect the nails, causing them to crumble, become thickened and lift away 
from the nail bed which can be painful.   
 
Humira is used to treat moderate to severe chronic plaque psoriasis in adults.   
 
Hidradenitis suppurativa 
 
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic and often painful inflammatory skin 
disease. Symptoms may include tender nodules (lumps) and abscesses (boils) that may leak pus. It most 
commonly affects specific areas of the skin, such as under the breasts, the armpits, inner thighs, groin and 
buttocks. Scarring may also occur in affected areas. 
 
Humira is used to treat  

 moderate to severe hidradenitis suppurativa in adults and 
 moderate to severe hidradenitis suppurativa in adolescents aged 12to 17 years. 
 

Humira can reduce the number of nodules and abscesses caused by the disease and the pain that is often 
associated with the disease. You may first be given other medicines. If you do not respond well enough to 
these medicines, you will be given Humira. 
 
Crohn’s disease 
 
Crohn’s disease is an inflammatory disease of the digestive tract. 
 
Humira is used to treat  

 moderate to severe Crohn’s disease in adults and  
 moderate to severe Crohn’s disease in children and adolescents aged 6 to 17 years.  

 
You may first be given other medicines. If you do not respond well enough to these medicines, you will be 
given Humira. 
 
Ulcerative colitis 
 
Ulcerative colitis is an inflammatory disease of the large intestine. 
 
Humira is used to treat  

 moderate to severe ulcerative colitis in adults and  
 moderate to severe ulcerative colitis in children and adolescents aged 6 to 17 years 



493 

 
You may first be given other medicines. If you do not respond well enough to these medicines, you will be 
given Humira. 
 
Non-infectious uveitis 

 
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. 
 
Humira is used to treat  

 adults with non-infectious uveitis with inflammation affecting the back of the eye  
 children with chronic non-infectious uveitis from 2 years of age with inflammation affecting the 

front of the eye  
 

This inflammation may lead to a decrease of vision and/or the presence of floaters in the eye (black dots or 
wispy lines that move across the field of vision). Humira works by reducing this inflammation. You may 
first be given other medicines. If you do not respond well enough to these medicines, you will be given 
Humira. 
 
 
2. What you need to know before you use Humira 
 
Do not use Humira: 
 

 If you are allergic to adalimumab or any of the other ingredients of this medicine (listed in section 
6).  

 
 If you have active tuberculosis or other severe infections (see “Warnings and precautions”). It is 

important that you tell your doctor if you have symptoms of infections, for example, fever, 
wounds, feeling tired, dental problems. 

 
 If you have moderate or severe heart failure. It is important to tell your doctor if you have had or 

have a serious heart condition (see “Warnings and precautions”). 
 
Warnings and precautions 
  
Talk to your doctor or pharmacist before using Humira. 
 
Allergic reactions 
 

 If you get allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling 
or rash do not inject more Humira and contact your doctor immediately since, in rare cases, these 
reactions can be life threatening.  

 
Infections 
 

 If you have an infection, including long-term infection or an infection in one part of the body (for 
example, leg ulcer) consult your doctor before starting Humira. If you are unsure, contact your 
doctor.  

 
 You might get infections more easily while you are receiving Humira treatment. This risk may 

increase if you have problems with your lungs. These infections may be serious and include: 
 

 tuberculosis 



494 

 infections caused by viruses, fungi, parasites or bacteria 
 severe infection in the blood (sepsis) 

 
In rare cases, these infections can be life-threatening. It is important to tell your doctor if you get 
symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may tell you to 
stop using Humira for some time. 

 
 Tell your doctor if you live or travel in regions where fungal infections (for example, 

histoplasmosis, coccidioidomycosis or blastomycosis) are very common. 
 

 Tell your doctor if you have had infections which keep coming back or other conditions that 
increase the risk of infections. 

 
 If you are over 65 years you may be more likely to get infections while taking Humira. You and 

your doctor should pay special attention to signs of infection while you are being treated with 
Humira. It is important to tell your doctor if you get symptoms of infections, such as fever, 
wounds, feeling tired or dental problems. 

 
Tuberculosis 
 

 It is very important that you tell your doctor if you have ever had tuberculosis, or if you have been 
in close contact with someone who has had tuberculosis. If you have active tuberculosis, do not 
use Humira. 

 
 As cases of tuberculosis have been reported in patients treated with Humira, your doctor 

will check you for signs and symptoms of tuberculosis before starting Humira. This will 
include a thorough medical evaluation including your medical history and appropriate 
screening tests (for example, chest X-ray and a tuberculin test). The conduct and results of 
these tests should be recorded on your Patient Reminder Card.   

 Tuberculosis can develop during therapy even if you have received treatment for the 
prevention of tuberculosis.  

 If symptoms of tuberculosis (for example, cough that does not go away, weight loss, lack 
of energy, mild fever), or any other infection appear during or after therapy tell your 
doctor immediately.  

 
Hepatitis B 
 

 Tell your doctor if you are a carrier of the hepatitis B virus (HBV), if you have active HBV or if 
you think you might be at risk of getting HBV.   

 
 Your doctor should test you for HBV. In people who carry HBV, Humira can cause the 

virus to become active again.  
 In some rare cases, especially if you are taking other medicines that suppress the immune 

system, reactivation of HBV can be life-threatening.  
 
Surgery or dental procedure 
 

 If you are about to have surgery or dental procedures please inform your doctor that you are taking 
Humira. Your doctor may recommend temporary discontinuation of Humira. 

 



495 

Demyelinating disease 
 

 If you have or develop a demyelinating disease (a disease that affects the insulating layer around 
the nerves, such as multiple sclerosis), your doctor will decide if you should receive or continue to 
receive Humira. Tell your doctor immediately if you experience symptoms like changes in your 
vision, weakness in your arms or legs or numbness or tingling in any part of your body. 

 
Vaccinations 
 

 Certain vaccines may cause infections and should not be given while receiving Humira.   
 

 Check with your doctor before you receive any vaccines.  
 It is recommended that children, if possible, be given all the scheduled vaccinations for 

their age before they start treatment with Humira.  
 If you received Humira while you were pregnant, your baby may be at higher risk for 

getting such an infection for up to approximately five months after the last Humira dose 
you received during pregnancy. It is important that you tell your baby's doctors and other 
health care professionals about your Humira use during your pregnancy so they can 
decide when your baby should receive any vaccine. 

 
Heart failure 
 

 If you have mild heart failure and are being treated with Humira, your heart failure status must be 
closely monitored by your doctor. It is important to tell your doctor if you have had or have a 
serious heart condition. If you develop new or worsening symptoms of heart failure (e.g. shortness 
of breath, or swelling of your feet), you must contact your doctor immediately. Your doctor will 
decide if you should receive Humira. 

 
Fever, bruising, bleeding or looking pale 
 

 In some patients the body may fail to produce enough of the blood cells that fight off infections or 
help you to stop bleeding. Your doctor may decide to stop treatment. If you develop a fever that 
does not go away, develop light bruises or bleed very easily or look very pale, call your doctor 
right away. 

 
Cancer 
 

 There have been very rare cases of certain kinds of cancer in children and adult patients taking 
Humira or other TNF blockers.  

 
 People with more serious rheumatoid arthritis that have had the disease for a long time 

may have a higher than average risk of getting lymphoma (a cancer that affects the lymph 
system) and leukaemia (a cancer that affects the blood and bone marrow).  

 If you take Humira the risk of getting lymphoma, leukaemia, or other cancers may 
increase. On rare occasions, an uncommon and severe type of lymphoma has been seen in 
patients taking Humira. Some of those patients were also treated with azathioprine or 6- 
mercaptopurine.  

 Tell your doctor if you are taking azathioprine or 6-mercaptopurine with Humira.  
 Cases of non-melanoma skin cancer have been observed in patients taking Humira.  
 If new skin lesions appear during or after therapy or if existing lesions change appearance, 

tell your doctor. 
 



496 

 There have been cases of cancers, other than lymphoma, in patients with a specific type of lung 
disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another TNF blocker. 
If you have COPD, or are a heavy smoker, you should discuss with your doctor whether treatment 
with a TNF blocker is appropriate for you. 

 
Autoimmune disease 
 

 On rare occasions, treatment with Humira could result in lupus-like syndrome. Contact your 
doctor if symptoms such as persistent unexplained rash, fever, joint pain or tiredness occur. 

 
Children and adolescents 
 

 Vaccinations: if possible, children should be up to date with all vaccinations before using Humira. 
 

Other medicines and Humira 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 
 
You should not take Humira with medicines containing the following active substances due to increased 
risk of serious infection: 

 anakinra 
 abatacept. 

 
Humira can be taken together with: 

 methotrexate  
 certain disease-modifying anti-rheumatic agents (for example, sulfasalazine, hydroxychloroquine, 

leflunomide and injectable gold preparations) 
 steroids or pain medications including non-steroidal anti-inflammatory drugs (NSAIDs). 

 
If you have questions, please ask your doctor.  
 
Pregnancy and breast-feeding 
 

 You should consider the use of adequate contraception to prevent pregnancy and continue its use 
for at least 5 months after the last Humira treatment. 

 If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for 
advice about taking this medicine. 

 Humira should only be used during a pregnancy if needed. 
 According to a pregnancy study, there was no higher risk of birth defects when the mother had 

received Humira during pregnancy compared with mothers with the same disease who did not 
receive Humira. 

 Humira can be used during breast-feeding. 
 If you receive Humira during your pregnancy, your baby may have a higher risk for getting an 

infection. 
 It is important that you tell your baby’s doctors and other health care professionals about your 

Humira use during your pregnancy before the baby receives any vaccine.  For more information 
on vaccines see the “Warnings and precautions” section. 

 
Driving and using machines 
 
Humira may have a small effect on your ability to drive, cycle or use machines. Room spinning sensation 
and vision disturbances may occur after taking Humira. 



497 

 
 
3. How to use Humira 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are not sure.  
 
The recommended doses for Humira in each of the approved uses are shown in the following table. Your 
doctor may prescribe another strength of Humira if you need a different dose. 
 

Rheumatoid arthritis 
Age or body weight How much and how often to 

take?
Notes 

Adults  40 mg every other week In rheumatoid arthritis, 
methotrexate is continued while 
using Humira. If your doctor 
decides that methotrexate is 
inappropriate, Humira can be 
given alone. 
 
If you have rheumatoid arthritis 
and you do not receive 
methotrexate with your Humira 
therapy, your doctor may decide 
to give Humira 40 mg every 
week or 80 mg every other 
week. 

 
Plaque psoriasis 
Age or body weight How much and how often to 

take?
Notes 

Adults 
 

First dose of 80 mg (one 80 mg 
injection), followed by 40 mg 
every other week starting one 
week after the first dose. 

If you have an inadequate 
response, your doctor may 
increase the dosage to 40 mg 
every week or 80 mg every 
other week. 

 



498 

Hidradenitis suppurativa 
Age or body weight How much and how often to 

take?
Notes 

Adults First dose of 160 mg (two 
80 mg injections in one day or 
one 80 mg injection per day for 
two consecutive days), followed 
by an 80 mg dose (one 80 mg 
injection) two weeks later. After 
two further weeks, continue 
with a dose of 40 mg every 
week or 80 mg every other 
week, as prescribed by your 
doctor.  

It is recommended that you use 
an antiseptic wash daily on the 
affected areas. 
 

Adolescents from 12 to 17 years 
of age weighing 30 kg or more 

First dose of 80 mg (one 80 mg 
injection), followed by 40 mg 
every other week starting one 
week later.   

If you have an inadequate 
response to Humira 40 mg every 
other week, your doctor may 
increase the dosage to 40 mg 
every week or 80 mg every 
other week.  
 
It is recommended that you use 
an antiseptic wash daily on the 
affected areas. 

 
Crohn’s disease 
Age or body weight How much and how often to 

take?
Notes 

Children, adolescents and adults 
from 6 years of age weighing 40 
kg or more 

First dose of 80 mg (one 80 mg 
injection), followed by 40 mg 
two weeks later. 
 
If a faster response is required, 
the doctor may prescribe a first 
dose of 160 mg (two 80 mg 
injections in one day or one 
80 mg injection per day for two 
consecutive days), followed by 
80 mg (one 80 mg injection) 
two weeks later. 
 
Thereafter, the usual dose is 
40 mg every other week.

Your doctor may increase the 
dosage to 40 mg every week or 
80 mg every other week. 
 



499 

Children and adolescents from 6 
to 17  years of age weighing less 
than 40 kg 

First dose of 40 mg, followed by 
20 mg two weeks later.  
 
If a faster response is required, 
the doctor may prescribe a first 
dose of 80 mg (one 80 mg 
injection), followed by 40 mg 
two weeks later. 
 
Thereafter, the usual dose is 
20 mg every other week.

Your doctor may increase the 
dose frequency to 20 mg every 
week. 
 

 
Ulcerative colitis 
Age or body weight How much and how often to 

take?
Notes 

Adults First dose of 160 mg (two 
80 mg injections in one day or 
one 80 mg injection per day for 
two consecutive days), followed 
by 80 mg (one 80 mg injection) 
two weeks later. 
 
Thereafter, the usual dose is 
40 mg every other week.

Your doctor may increase the 
dosage to 40 mg every week or 
80 mg every other week. 

Children and adolescents from 6 
years of age weighing less than 
40 kg 

First dose of 80 mg (one 80 mg 
injection), followed by 40 mg 
(one 40 mg injection) two 
weeks later. 
 
Thereafter, the usual dose is 40 
mg every other week.

You should continue taking 
Humira at your usual dose, even 
after turning 18 years of age. 

Children and adolescents from 6 
years of age weighing 40 kg or 
more 

First dose of 160 mg (two 80 
mg injections in one day or one 
80 mg injection per day for two 
consecutive days), followed by 
80 mg (one 80 mg injection) 
two weeks later. 
 
Thereafter, the usual dose is 80 
mg every other week.

You should continue taking 
Humira at your usual dose, even 
after turning 18 years of age. 

 
Non-infectious uveitis 
Age or body weight How much and how often to 

take?
Notes 

Adults First dose of 80 mg (one 80 mg 
injection), followed by 40 mg 
every other week starting one 
week after the first dose. 

Corticosteroids or other 
medicines that influence the 
immune system may be 
continued while using Humira. 
Humira can also be given alone.

Children and adolescents from 
2 years of age weighing less 
than 30 kg 
 

20 mg every other week Your doctor may prescribe an 
initial dose of 40 mg to be 
administered one week prior to 
the start of the usual dose of 



500 

20 mg every other week. 
Humira is recommended for use 
in combination with 
methotrexate. 

Children and adolescents from 
2 years of age weighing 30 kg 
or more 
 

40 mg every other week  Your doctor may prescribe an 
initial dose of 80 mg to be 
administered one week prior to 
the start of the usual dose of 
40 mg every other week. 
Humira is recommended for use 
in combination with 
methotrexate. 

 
Method and route of administration 
 
Humira is administered by injection under the skin (by subcutaneous injection). 
 
Detailed instructions on how to inject Humira are provided in section 7 ‘Injecting Humira’. 
 
If you use more Humira than you should 
 
If you accidentally inject Humira more frequently than told to by your doctor or pharmacist, call your 
doctor or pharmacist and tell them that you have taken more. Always take the outer carton of the medicine 
with you, even if it is empty.  
 
If you forget to use Humira 
 
If you forget to give yourself an injection, you should inject the next dose of Humira as soon as you 
remember. Then take your next dose as you would have on your originally scheduled day, had you not 
forgotten a dose.  
 
If you stop using Humira 
 
The decision to stop using Humira should be discussed with your doctor. Your symptoms may return if 
you stop using Humira. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side 
effects are mild to moderate. However, some may be serious and require treatment. Side effects may occur 
at least up to 4 months after the last Humira injection.   
 
Tell your doctor immediately if you notice any of the following 
 
 severe rash, hives or other signs of allergic reaction 
 swollen face, hands, feet 
 trouble breathing, swallowing 
 shortness of breath with physical activity or upon lying down or swelling of the feet 
 
Tell your doctor as soon as possible if you notice any of the following 



501 

 
 signs of infection such as fever, feeling sick, wounds, dental problems, burning on urination 
 feeling weak or tired 
 coughing 
 tingling 
 numbness 
 double vision 
 arm or leg weakness 
 a bump or open sore that doesn't heal 
 signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, 

paleness 
 
The symptoms described above can be signs of the below listed side effects, which have been observed 
with Humira. 
 
Very common (may affect more than 1 in 10 people)  
 
 injection site reactions (including pain, swelling, redness or itching) 
 respiratory tract infections (including cold, runny nose, sinus infection, pneumonia) 
 headache 
 abdominal pain 
 nausea and vomiting 
 rash 
 musculoskeletal pain 
 
Common (may affect up to 1 in 10 people) 
 
 serious infections (including blood poisoning and influenza) 
 intestinal infections (including gastroenteritis) 
 skin infections (including cellulitis and shingles) 
 ear infections 
 oral infections (including tooth infections and cold sores) 
 reproductive tract infections 
 urinary tract infection 
 fungal infections 
 joint infections 
 benign tumours 
 skin cancer 
 allergic reactions (including seasonal allergy) 
 dehydration 
 mood swings (including depression) 
 anxiety 
 difficulty sleeping 
 sensation disorders such as tingling, prickling or numbness 
 migraine 
 nerve root compression (including low back pain and leg pain) 
 vision disturbances 
 eye inflammation 
 inflammation of the eye lid and eye swelling 
 vertigo (feeling of dizziness or spinning) 
 sensation of heart beating rapidly 



502 

 high blood pressure 
 flushing 
 haematoma (collection of blood outside of blood vessels) 
 cough 
 asthma 
 shortness of breath 
 gastrointestinal bleeding 
 dyspepsia (indigestion, bloating, heart burn) 
 acid reflux disease 
 sicca syndrome (including dry eyes and dry mouth) 
 itching 
 itchy rash 
 bruising 
 inflammation of the skin (such as eczema) 
 breaking of finger nails and toe nails 
 increased sweating 
 hair loss 
 new onset or worsening of psoriasis 
 muscle spasms 
 blood in urine 
 kidney problems 
 chest pain 
 oedema (swelling) 
 fever 
 reduction in blood platelets which increases risk of bleeding or bruising 
 impaired healing 
 
Uncommon (may affect up to 1 in 100 people) 
 
 opportunistic infections (which include tuberculosis and other infections that occur when resistance 

to disease is lowered) 
 neurological infections (including viral meningitis) 
 eye infections 
 bacterial infections 
 diverticulitis (inflammation and infection of the large intestine) 
 cancer 
 cancer that affects the lymph system 
 melanoma 
 immune disorders that could affect the lungs, skin and lymph nodes (most commonly presenting as 

sarcoidosis) 
 vasculitis (inflammation of blood vessels) 
 tremor (shaking) 
 neuropathy (disorder of the nerves) 
 stroke 
 hearing loss, buzzing 
 sensation of heart beating irregularly such as skipped beats 
 heart problems that can cause shortness of breath or ankle swelling 
 heart attack 
 a sac in the wall of a major artery, inflammation and clot of a vein; blockage of a blood vessel 
 lung diseases causing shortness of breath (including inflammation) 



503 

 pulmonary embolism (blockage in an artery of the lung) 
 pleural effusion (abnormal collection of fluid in the pleural space) 
 inflammation of the pancreas which causes severe pain in the abdomen and back 
 difficulty in swallowing 
 facial oedema (swelling of the face) 
 gallbladder inflammation, gallbladder stones 
 fatty liver 
 night sweats 
 scar 
 abnormal muscle breakdown 
 systemic lupus erythematosus (including inflammation of skin, heart, lung, joints and other organ 

systems) 
 sleep interruptions 
 impotence 
 inflammations 
 
Rare (may affect up to 1 in 1,000 people) 
 
 leukaemia (cancer affecting the blood and bone marrow) 
 severe allergic reaction with shock 
 multiple sclerosis 
 nerve disorders (such as eye nerve inflammation and Guillain-Barré syndrome that may cause 

muscle weakness, abnormal sensations, tingling in the arms and upper body) 
 heart stops pumping 
 pulmonary fibrosis (scarring of the lung) 
 intestinal perforation (hole in the intestine) 
 hepatitis 
 reactivation of hepatitis B 
 autoimmune hepatitis (inflammation of the liver caused by the body's own immune system) 
 cutaneous vasculitis (inflammation of blood vessels in the skin) 
 Stevens-Johnson syndrome (early symptoms include malaise, fever, headache and rash) 
 facial oedema (swelling of the face) associated with allergic reactions 
 erythema multiforme (inflammatory skin rash) 
 lupus-like syndrome 
 angioedema (localized swelling of the skin) 
 lichenoid skin reaction (itchy reddish-purple skin rash) 
 
Not known (frequency cannot be estimated from the available data) 
 
 hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal) 
 Merkel cell carcinoma (a type of skin cancer) 
 Kaposi’s sarcoma, a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma 

most commonly appears as purple lesions on the skin 
 liver failure 
 worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle         

weakness) 
 
Some side effects observed with Humira may not have symptoms and may only be discovered through 
blood tests. These include: 
 
Very common (may affect more than 1 in 10 people)  



504 

 
 low blood measurements for white blood cells 
 low blood measurements for red blood cells 
 increased lipids in the blood 
 elevated liver enzymes 
 
Common (may affect up to 1 in 10 people) 
 
 high blood measurements for white blood cells   
 low blood measurements for platelets 
 increased uric acid in the blood 
 abnormal blood measurements for sodium 
 low blood measurements for calcium 
 low blood measurements for phosphate 
 high blood sugar 
 high blood measurements for lactate dehydrogenase 
 autoantibodies present in the blood 
 low blood potassium 
 
Uncommon (may affect up to 1 in 100 people)  
 
 elevated bilirubin measurement (liver blood test) 
 
Rare (may affect up to 1 in 1,000 people) 
 
 low blood measurements for white blood cells, red blood cells and platelet count 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects, you can help provide more information on the safety of this 
medicine. 
 
 
5. How to store Humira 
 
Keep this medicine out of the sight and reach of children.  
 
Do not use this medicine after the expiry date stated on the label/blister/carton after EXP.  
 
Store in a refrigerator (2C – 8C). Do not freeze.  
 
Keep the pre-filled syringe in the outer carton in order to protect from light. 
 
Alternative Storage: 
 
When needed (for example when you are travelling), a single Humira pre-filled syringe may be stored at 
room temperature (up to 25°C) for a maximum period of 14 days – be sure to protect it from light. Once 
removed from the refrigerator for room temperature storage, the syringe must be used within 14 days or 
discarded, even if it is returned to the refrigerator.   
 



505 

You should record the date when the syringe is first removed from refrigerator and the date after which it 
should be discarded.   
 
Do not throw away any medicines via wastewater or household waste. Ask your doctor or pharmacist how 
to throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Humira contains 
 
The active substance is adalimumab. 
The other ingredients are mannitol, polysorbate 80 and water for injections. 
 
What the Humira pre-filled syringe with automatic needle guard looks like and contents of the pack 
 
Humira 80 mg solution for injection in pre-filled syringe with automatic needle guard is supplied as a 
sterile solution of 80 mg adalimumab dissolved in 0.8 ml solution. 
 
The Humira pre-filled syringe is a glass syringe containing a solution of adalimumab.  
 
The Humira pre-filled syringe is available in a pack containing 1 pre-filled syringe for patient use with 1 
alcohol pad.   
 
Humira may be available as a vial, a pre-filled syringe and/or a pre-filled pen. 
 
Marketing Authorisation Holder 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany   
 
Manufacturer  
 
AbbVie Biotechnology GmbH 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
AbbVie SA 
Tél/Tel: +32 10  477811 

Lietuva 
AbbVie UAB  
Tel: +370 5 205 3023 

България 
АбВи ЕООД 
Тел.:+359 2 90 30 430 

Luxembourg/Luxemburg 
AbbVie SA 
Belgique/Belgien 
Tél/Tel: +32 10 477811

Česká republika 
AbbVie s.r.o.  
Tel: +420 233 098 111 

Magyarország 
AbbVie Kft. 
Tel.:+36 1 455 8600



506 

Danmark 
AbbVie A/S 
Tlf: +45 72 30-20-28 

Malta 
V.J.Salomone Pharma Limited  
Tel: +356 22983201

Deutschland 
AbbVie Deutschland GmbH & Co. KG 
Tel: 00800 222843 33 (gebührenfrei) 
Tel: +49 (0) 611 / 1720-0

Nederland 
AbbVie B.V. 
Tel:  +31 (0)88 322 2843 

Eesti 
AbbVie Biopharmaceuticals GmbH Eesti filiaal  
Tel: +372 623 1011 

Norge 
AbbVie AS 
Tlf: +47 67 81 80 00

Ελλάδα 
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. 
Τηλ: +30 214 4165 555

Österreich 
AbbVie GmbH  
Tel: +43 1 20589-0

España 
AbbVie Spain, S.L.U. 
Tel:  +34 91 384 09 10 

Polska 
AbbVie Polska Sp. z o.o. 
Tel.: +48 22 372 78 00 

France 
AbbVie 
Tél: +33 (0) 1 45 60 13 00 

Portugal 
AbbVie, Lda.  
Tel: +351 (0)21 1908400 

Hrvatska  
AbbVie d.o.o. 
Tel + 385 (0)1 5625 501

România 
AbbVie S.R.L. 
Tel: +40 21 529 30 35

Ireland 
AbbVie Limited  
Tel: +353 (0)1 4287900

Slovenija 
AbbVie Biofarmacevtska družba d.o.o. 
Tel: +386 (1)32 08 060

Ísland 
Vistor hf. 
Tel: +354 535 7000 

Slovenská republika 
AbbVie s.r.o. 
Tel: +421 2 5050 0777

Italia 
AbbVie S.r.l.  
Tel: +39 06 928921 

Suomi/Finland 
AbbVie Oy  
Puh/Tel:  +358 (0)10 2411 200 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Τηλ.: +357 22 34 74 40

Sverige 
AbbVie AB 
Tel:  +46 (0)8 684 44 600

Latvija 
AbbVie SIA  
Tel: +371 67605000 

United Kingdom 
AbbVie Ltd  
Tel: +44 (0)1628 561090

 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the 
local representative of the Marketing Authorisation Holder. 
 
 
7. Injecting Humira  
 

 The following instructions explain how to give yourself a subcutaneous injection of Humira using 
the pre-filled syringe. First read all the instructions carefully and then follow them step by step.  
 



507 

 You will be instructed by your doctor, nurse or pharmacist on the technique of self-injection.  
 

 Do not attempt to self-inject until you are sure that you understand how to prepare and give the 
injection.  
 

 After proper training, the injection can be given by yourself or given by another person, for 
example, a family member or friend.   
 

 Only use each pre-filled syringe for one injection. 
 
Humira Pre-filled Syringe 
 
        Plunger    Finger Grip           Needle Cover 

 
 
Do not use the pre-filled syringe and call your doctor or pharmacist if the 
 

 liquid is cloudy, discoloured, or has flakes or particles in it 
 expiry (EXP) date has passed 
 liquid has been frozen or left in direct sunlight 
 pre-filled syringe has been dropped or crushed 

 
Do not remove the needle cover until just before injection. Keep Humira out of the sight and reach 
of children. 
 

STEP 1 
 
Take Humira out of the refrigerator. 
 
Leave Humira at room temperature for 15 to 30 minutes before injecting. 
 

 Do not remove the needle cover while allowing Humira to reach room temperature 
 Do not warm Humira in any other way. For example, do not warm it in a microwave or in hot 

water 



508 

STEP 2  
 
           Syringe 

                 Pad 

Check the expiry (EXP) date. Do not use the pre-filled 
syringe if expiry (EXP) date has passed. 
 
Place the following on a clean, flat surface 
 

 1 single-use pre-filled syringe and  
 1 alcohol pad 

 
Wash and dry your hands. 

STEP 3 
 
Injectable Areas 

     Injectable Areas 

Choose an injection site: 
 

 On the front of your thighs or 
 Your belly (abdomen) at least 5 cm from your belly 

button (navel) 
 At least 3 cm from your last injection site 

 
Wipe the injection site in a circular motion with the alcohol 
pad. 
 

 Do not inject through clothes 
 Do not inject into skin that is sore, bruised, red, 

hard, scarred, has stretch marks, or areas with 
psoriasis plaques 

 
 



509 

STEP 4 

 

Hold the pre-filled syringe in one hand between the finger 
grip and the needle cover. 
 
Check the liquid in the pre-filled syringe. 
 

 Make sure the liquid is clear and colourless 
 Do not use the pre-filled syringe if the liquid is 

cloudy or has particles 
 Do not use the pre-filled syringe if it has been 

dropped or crushed 
 

Gently pull the needle cover straight off with the other hand. 
Throw the needle cover away. Do not recap. 
 

 Do not hold or pull the plunger when removing the 
needle cover 

 Do not touch the needle with your fingers or let the 
needle touch anything 

 It is normal to see a drop of liquid at the end of the 
needle

STEP 5 Hold the body of the pre-filled syringe in one hand between 
the thumb and index fingers, like you would a pencil. 
 
Squeeze the skin at your injection site with your other hand 
to make a raised area and hold it firmly. 

 

STEP 6 

 

Insert the needle all the way into the skin at about a 45-
degree angle with one quick, short motion. 
 

 After the needle is in, let go of the skin you are 
holding  

 
Slowly push the plunger all the way in until all of the liquid 
is injected and the pre-filled syringe is empty. 
 



510 

STEP 7 

 

When the injection is completed, slowly pull the needle out 
of the skin while keeping the pre-filled syringe at the same 
angle. 
 
Slowly take your thumb off the plunger. The needle will 
then be covered by the automatic needle guard.  
 The automatic needle guard will not activate unless all the 

liquid is injected 

 Speak to your doctor, pharmacist or nurse if you think 
you have not given a full dose  

After completing the injection, place a cotton ball or gauze 
pad on the skin over the injection site. 
 

 Do not rub 
 Slight bleeding at the injection site is normal 

STEP 8 
 
Throw away the used pre-filled syringe in a special disposal container as instructed by your doctor, 
nurse or pharmacist. Never recap a needle. 
 

 Do not recycle or throw the pre-filled syringe in the household waste 
 Always keep the pre-filled syringe and the special disposal container out of the sight and 

reach of children 
 

The needle cover, alcohol pad, cotton ball or gauze pad, blister and packaging may be put in your 
household waste. 

 



511 

Package leaflet: Information for the patient 
 

Humira 80 mg solution for injection in pre-filled pen 
adalimumab 

 
Read all of this leaflet carefully before you start using this medicine because it contains important 
information for you. 
 Keep this leaflet. You may need to read it again. 
 Your doctor will also give you a Patient Reminder Card, which contains important safety 

information that you need to be aware of before you begin using Humira and during treatment with 
Humira. Keep this Patient Reminder Card with you. 

 If you have any questions, ask your doctor or pharmacist. 
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even 

if their signs of illness are the same as yours. 
 If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet  
1. What Humira is and what it is used for 
2. What you need to know before you use Humira 
3. How to use Humira 
4. Possible side effects 
5 How to store Humira 
6. Contents of the pack and other information 
7. Injecting Humira 
 
 
1. What Humira is and what it is used for 
 
Humira contains the active substance adalimumab. 
 
Humira is used to treat 

 Rheumatoid arthritis 
 Plaque psoriasis 
 Hidradenitis suppurativa 
 Crohn’s disease 
 Ulcerative colitis 
 Non-infectious uveitis 

 
The active ingredient in Humira, adalimumab, is a human monoclonal antibody. Monoclonal antibodies 
are proteins that attach to a specific target. 
 
The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the 
immune (defence) system and is present at increased levels in the inflammatory diseases listed above. By 
attaching to TNFα, Humira decreases the process of inflammation in these diseases. 
 
Rheumatoid arthritis 
 
Rheumatoid arthritis is an inflammatory disease of the joints. 
 



512 

Humira is used to treat moderate to severe rheumatoid arthritis in adults. You may first be given other 
disease-modifying medicines, such as methotrexate. If you do not respond well enough to these medicines, 
you will be given Humira. 
 
Humira can also be used to treat severe, active and progressive rheumatoid arthritis without previous 
methotrexate treatment. 
 
Humira can slow down the damage to the joints caused by the inflammatory disease and can help them 
move more freely.  
 
Your doctor will decide if Humira should be used with methotrexate or alone. 
 
Plaque psoriasis  
 
Plaque psoriasis is a skin condition that causes red, flaky, crusty patches of skin covered with silvery 
scales. Plaque psoriasis can also affect the nails, causing them to crumble, become thickened and lift away 
from the nail bed which can be painful.   
 
Humira is used to treat moderate to severe chronic plaque psoriasis in adults. 
 

Hidradenitis suppurativa 
 
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic and often painful inflammatory skin 
disease. Symptoms may include tender nodules (lumps) and abscesses (boils) that may leak pus. It most 
commonly affects specific areas of the skin, such as under the breasts, the armpits, inner thighs, groin and 
buttocks. Scarring may also occur in affected areas. 
 
Humira is used to treat  

 moderate to severe hidradenitis suppurativa in adults and 
 moderate to severe hidradenitis suppurativa in adolescents aged 12 to 17 years.  

 
Humira can reduce the number of nodules and abscesses caused by the disease and the pain that is often 
associated with the disease. You may first be given other medicines. If you do not respond well enough to 
these medicines, you will be given Humira. 
 
Crohn’s disease 
 
Crohn’s disease is an inflammatory disease of the digestive tract. 
 
Humira is used to treat 

 moderate to severe Crohn’s disease in adults and  
 moderate to severe Crohn’s disease in children and adolescents aged 6 to 17 years. 
 

You may first be given other medicines. If you do not respond well enough to these medicines, you will be 
given Humira. 

 
Ulcerative colitis 
 
Ulcerative colitis is an inflammatory disease of the large intestine. 
 
Humira is used to treat  

 moderate to severe ulcerative colitis in adults and  
 moderate to severe ulcerative colitis in children and adolescents aged 6 to 17 years 



513 

 
You may first be given other medicines. If you do not respond well enough to these medicines, you will be 
given Humira. 
 
Non-infectious uveitis 
 
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. 
 
Humira is used to treat  

 adults with non-infectious uveitis with inflammation affecting the back of the eye  
 children with chronic non-infectious uveitis from 2 years of age with inflammation affecting the 

front of the eye 
 
This inflammation may lead to a decrease of vision and/or the presence of floaters in the eye (black dots or 
wispy lines that move across the field of vision). Humira works by reducing this inflammation. You may 
first be given other medicines. If you do not respond well enough to these medicines, you will be given 
Humira.  
 
 
2. What you need to know before you use Humira 
 
Do not use Humira: 
 

 If you are allergic to adalimumab or any of the other ingredients of this medicine (listed in section 
6).  

 
 If you have active tuberculosis or other severe infections (see “Warnings and precautions”). It is 

important that you tell your doctor if you have symptoms of infections, for example, fever, 
wounds, feeling tired, dental problems. 

 
 If you have moderate or severe heart failure. It is important to tell your doctor if you have had or 

have a serious heart condition (see “Warnings and precautions”). 
 
Warnings and precautions 
 
Talk to your doctor or pharmacist before using Humira. 
 
Allergic reactions 
 

 If you get allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling 
or rash do not inject more Humira and contact your doctor immediately since, in rare cases, these 
reactions can be life threatening. 

 
Infections 
 

 If you have an infection, including long-term infection or an infection in one part of the body (for 
example, leg ulcer) consult your doctor before starting Humira. If you are unsure, contact your 
doctor.  

 
 You might get infections more easily while you are receiving Humira treatment. This risk may 

increase if you have problems with your lungs. These infections may be serious and include:  
 tuberculosis 



514 

 infections caused by viruses, fungi, parasites or bacteria 
 severe infection in the blood (sepsis) 

 
In rare cases, these infections can be life-threatening. It is important to tell your doctor if you get 
symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may tell you to 
stop using Humira for some time. 
 

 Tell your doctor if you live or travel in regions where fungal infections (for example, 
histoplasmosis, coccidioidomycosis or blastomycosis) are very common. 

 
 Tell your doctor if you have had infections which keep coming back or other conditions that 

increase the risk of infections. 
 

 If you are over 65 years you may be more likely to get infections while taking Humira. You and 
your doctor should pay special attention to signs of infection while you are being treated with 
Humira. It is important to tell your doctor if you get symptoms of infections, such as fever, 
wounds, feeling tired or dental problems. 

 
Tuberculosis 
 

 It is very important that you tell your doctor if you have ever had tuberculosis, or if you have been 
in close contact with someone who has had tuberculosis. If you have active tuberculosis, do not 
use Humira. 

 
 As cases of tuberculosis have been reported in patients treated with Humira, your doctor 

will check you for signs and symptoms of tuberculosis before starting Humira. This will 
include a thorough medical evaluation including your medical history and appropriate 
screening tests (for example, chest X-ray and a tuberculin test). The conduct and results of 
these tests should be recorded on your Patient Reminder Card.  

 Tuberculosis can develop during therapy even if you have received treatment for the 
prevention of tuberculosis.  

 If symptoms of tuberculosis (for example, cough that does not go away, weight loss, lack 
of energy, mild fever), or any other infection appear during or after therapy tell your 
doctor immediately. 
 

Hepatitis B 
 

 Tell your doctor if you are a carrier of the hepatitis B virus (HBV), if you have active HBV or if 
you think you might be at risk of getting HBV.  

 Your doctor should test you for HBV. In people who carry HBV, Humira can cause the 
virus to become active again. 

 In some rare cases, especially if you are taking other medicines that suppress the immune 
system, reactivation of HBV can be life-threatening.   

 
Surgery or dental procedure 
 

 If you are about to have surgery or dental procedures please inform your doctor that you are taking 
Humira. Your doctor may recommend temporary discontinuation of Humira.  

 
Demyelinating disease 
 



515 

 If you have or develop a demyelinating disease (a disease that affects the insulating layer around 
the nerves, such as multiple sclerosis), your doctor will decide if you should receive or continue to 
receive Humira. Tell your doctor immediately if you experience symptoms like changes in your 
vision, weakness in your arms or legs or numbness or tingling in any part of your body. 

 
Vaccinations 
 

 Certain vaccines may cause infections and should not be given while receiving Humira.  
 

 Check with your doctor before you receive any vaccines.  
 It is recommended that children, if possible, be given all the scheduled vaccinations for 

their age before they start treatment with Humira. 
 If you received Humira while you were pregnant, your baby may be at higher risk for 

getting such an infection for up to approximately five months after the last Humira dose 
you received during pregnancy. It is important that you tell your baby's doctors and other 
health care professionals about your Humira use during your pregnancy so they can 
decide when your baby should receive any vaccine. 

 
Heart failure 
 

 If you have mild heart failure and are being treated with Humira, your heart failure status must be 
closely monitored by your doctor. It is important to tell your doctor if you have had or have a 
serious heart condition. If you develop new or worsening symptoms of heart failure (e.g. shortness 
of breath, or swelling of your feet), you must contact your doctor immediately. Your doctor will 
decide if you should receive Humira. 

 
Fever, bruising, bleeding or looking pale 
 

 In some patients the body may fail to produce enough of the blood cells that fight off infections or 
help you to stop bleeding. Your doctor may decide to stop treatment. If you develop a fever that 
does not go away, develop light bruises or bleed very easily or look very pale, call your doctor 
right away. 

 
Cancer 
 

 There have been very rare cases of certain kinds of cancer in children and adult patients taking 
Humira or other TNF blockers.   

 
 People with more serious rheumatoid arthritis that have had the disease for a long time 

may have a higher than average risk of getting lymphoma (a cancer that affects the lymph 
system) and leukaemia (a cancer that affects the blood and bone marrow).  

 If you take Humira the risk of getting lymphoma, leukaemia, or other cancers may 
increase. On rare occasions, an uncommon and severe type of lymphoma, has been seen in 
patients taking Humira. Some of those patients were also treated with azathioprine or 6-
mercaptopurine.  

 Tell your doctor if you are taking azathioprine or 6-mercaptopurine with Humira.  
 Cases of non-melanoma skin cancer have been observed in patients taking Humira.  
 If new skin lesions appear during or after therapy or if existing lesions change appearance, 

tell your doctor. 
 

 There have been cases of cancers, other than lymphoma in patients with a specific type of lung 
disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another TNF blocker. 



516 

If you have COPD, or are a heavy smoker, you should discuss with your doctor whether treatment 
with a TNF blocker is appropriate for you. 

 
Autoimmune disease 
 

 On rare occasions, treatment with Humira could result in lupus-like syndrome. Contact your 
doctor if symptoms such as persistent unexplained rash, fever, joint pain or tiredness occur. 

 
Children and adolescents 
 

 Vaccinations: if possible, children should be up to date with all vaccinations before using Humira. 
 

Other medicines and Humira 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 
 
You should not take Humira with medicines containing the following active substances due to increased 
risk of serious infection: 

 anakinra 
 abatacept. 

 
Humira can be taken together with: 

 methotrexate 
 certain disease-modifying anti-rheumatic agents (for example, sulfasalazine, hydroxychloroquine, 

leflunomide and injectable gold preparations) 
 steroids or pain medications including non-steroidal anti-inflammatory drugs (NSAIDs). 

 
If you have questions, please ask your doctor. 
 
Pregnancy and breast-feeding 
 

 You should consider the use of adequate contraception to prevent pregnancy and continue its use 
for at least 5 months after the last Humira treatment. 

 If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for 
advice about taking this medicine. 

 Humira should only be used during a pregnancy if needed. 
 According to a pregnancy study, there was no higher risk of birth defects when the mother had 

received Humira during pregnancy compared with mothers with the same disease who did not 
receive Humira. 

 Humira can be used during breast-feeding. 
 If you receive Humira during your pregnancy, your baby may have a higher risk for getting an 

infection. 
 It is important that you tell your baby’s doctors and other health care professionals about your 

Humira use during your pregnancy before the baby receives any vaccine. For more information on 
vaccines see the “Warnings and precautions” section. 

 
Driving and using machines 
 
Humira may have a small effect on your ability to drive, cycle or use machines. Room spinning sensation 
and vision disturbances may occur after taking Humira. 
 
 



517 

3. How to use Humira 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are not sure. 
 
The recommended doses for Humira in each of the approved uses are shown in the following table. Your 
doctor may prescribe another strength of Humira if you need a different dose. 
 

Rheumatoid arthritis 
Age or body weight How much and how often to 

take?
Notes 

Adults  40 mg every other week In rheumatoid arthritis, 
methotrexate is continued while 
using Humira. If your doctor 
decides that methotrexate is 
inappropriate, Humira can be 
given alone. 
 
If you have rheumatoid arthritis 
and you do not receive 
methotrexate with your Humira 
therapy, your doctor may decide 
to give Humira 40 mg every 
week or 80 mg every other 
week. 

 
Plaque psoriasis 
Age or body weight How much and how often to 

take?
Notes 

Adults  
 

First dose of 80 mg (one 80 mg 
injection), followed by 40 mg 
every other week starting one 
week after the first dose. 

If you have an inadequate 
response, your doctor may 
increase the dosage to 40 mg 
every week or 80 mg every 
other week. 

 
Hidradenitis suppurativa 
Age or body weight How much and how often to 

take?
Notes 

Adults  First dose of 160 mg (two 80 
mg injections in one day or one 
80 mg injection per day for two 
consecutive days), followed by 
an 80 mg dose (one 80 mg 
injection) two weeks later. After 
two further weeks, continue 
with a dose of 40 mg every 
week or 80 mg every other 
week, as prescribed by your 
doctor.  

It is recommended that you use 
an antiseptic wash daily on the 
affected areas. 
 



518 

Adolescents from 12 to 17 years 
of age weighing 30 kg or more 

First dose of 80 mg (one 80 mg 
injection), followed by 40 mg 
every other week starting one 
week later.   

If you have an inadequate 
response to Humira 40 mg every 
other week, your doctor may 
increase the dosage to 40 mg 
every week or 80 mg every 
other week.  
It is recommended that you use 
an antiseptic wash daily on the 
affected areas. 

 
Crohn’s disease 
Age or body weight How much and how often to 

take?
Notes 

Children, adolescents and adults 
from 6 to 17 years of age 
weighing 40 kg or more 

First dose of 80 mg (one 80 mg 
injection), followed by 40 mg 
two weeks later. 
 
If a faster response is required, 
the doctor may prescribe a first 
dose of 160 mg (two 80 mg 
injections in one day or one 
80 mg injection per day for two 
consecutive days), followed by 
80 mg (one 80 mg injection) 
two weeks later. 
 
Thereafter, the usual dose is 40 
mg every other week.

Your doctor may increase the 
dosage to 40 mg every week or 
80 mg every other week. 
 

Children and adolescents from 6 
to 17 years of age weighing less 
than 40 kg 

First dose of 40 mg, followed by 
20 mg two weeks later.  
If a faster response is required, 
the doctor may prescribe a first 
dose of 80 mg (one 80 mg 
injection), followed by 40 mg 
two weeks later. 
 
Thereafter, the usual dose is 20 
mg every other week.

Your doctor may increase the 
dose frequency to 20 mg every 
week. 
 

 
Ulcerative colitis 
Age or body weight How much and how often to 

take?
Notes 

Adults First dose of 160 mg (two 80 
mg injections in one day or one 
80 mg injection per day for two 
consecutive days), followed by 
80 mg (one 80 mg injection) 
two weeks later. 
 
Thereafter, the usual dose is 40 
mg every other week. 
 

Your doctor may increase the 
dosage to 40 mg every week or 
80 mg every other week. 



519 

Children and adolescents from 6 
years of age weighing less than 
40 kg 

First dose of 80 mg (one 80 mg 
injection), followed by 40 mg 
(one 40 mg injection) two 
weeks later. 
 
Thereafter, the usual dose is 40 
mg every other week.

You should continue taking 
Humira at your usual dose, even 
after turning 18 years of age. 

Children and adolescents from 6 
years of age weighing 40 kg or 
more 

First dose of 160 mg (two 80 
mg injections in one day or one 
80 mg injection per day for two 
consecutive days), followed by 
80 mg (one 80 mg injection) 
two weeks later. 
 
Thereafter, the usual dose is 80 
mg every other week.

You should continue taking 
Humira at your usual dose, even 
after turning 18 years of age. 

 
Non-infectious uveitis 
Age or body weight How much and how often to 

take?
Notes 

Adults First dose of 80 mg (one 80 mg 
injection), followed by 40 mg 
every other week starting one 
week after the first dose. 

Corticosteroids or other 
medicines that influence the 
immune system may be 
continued while using Humira. 
Humira can also be given alone.

Children and adolescents from 
2 years of age weighing less 
than 30 kg 
 

20 mg every other week Your doctor may prescribe an 
initial dose of 40 mg to be 
administered one week prior to 
the start of the usual dose of 
20 mg every other week. 
Humira is recommended for use 
in combination with 
methotrexate. 

Children and adolescents from 
2 years of age weighing 30 kg 
or more 
 

40 mg every other week  Your doctor may prescribe an 
initial dose of 80 mg to be 
administered one week prior to 
the start of the usual dose of 
40 mg every other week. 
Humira is recommended for use 
in combination with 
methotrexate. 

 
Method and route of administration 
 
Humira is administered by injection under the skin (by subcutaneous injection). 
 
Detailed instructions on how to inject Humira are provided in section 7 ‘Injecting Humira’. 
 
If you use more Humira than you should 
 



520 

If you accidentally inject Humira more frequently than told to by your doctor or pharmacist, call your 
doctor or pharmacist and tell them that you have taken more. Always take the outer carton of the medicine 
with you, even if it is empty.  
 
If you forget to use Humira 
 
If you forget to give yourself an injection, you should inject the next dose of Humira as soon as you 
remember. Then take your next dose as you would have on your originally scheduled day, had you not 
forgotten a dose.  
 
If you stop using Humira 
 
The decision to stop using Humira should be discussed with your doctor. Your symptoms may return if 
you stop using Humira. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side 
effects are mild to moderate. However, some may be serious and require treatment. Side effects may occur 
at least up to 4 months after the last Humira injection.  
 
Tell your doctor immediately if you notice any of the following 
 
 severe rash, hives or other signs of allergic reaction  
 swollen face, hands, feet 
 trouble breathing, swallowing 
 shortness of breath with physical activity or upon lying down or swelling of the feet 

 
Tell your doctor as soon as possible if you notice any of the following 
 
 signs of infection such as fever, feeling sick, wounds, dental problems, burning on urination 
 feeling weak or tired 
 coughing 
 tingling 
 numbness 
 double vision 
 arm or leg weakness 
 a bump or open sore that doesn't heal 
 signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, 

paleness 
 
The symptoms described above can be signs of the below listed side effects, which have been observed 
with Humira. 
 
Very common (may affect more than 1 in 10 people)   
 
 injection site reactions (including pain, swelling, redness or itching) 
 respiratory tract infections (including cold, runny nose, sinus infection, pneumonia) 
 headache 



521 

 abdominal pain 
 nausea and vomiting 
 rash 
 musculoskeletal pain 
 
Common (may affect up to 1 in 10 people)  
 
 serious infections (including blood poisoning and influenza) 
 intestinal infections (including gastroenteritis) 
 skin infections (including cellulitis and shingles) 
 ear infections 
 oral infections (including tooth infections and cold sores) 
 reproductive tract infections 
 urinary tract infection 
 fungal infections 
 joint infections 
 benign tumours 
 skin cancer 
 allergic reactions (including seasonal allergy) 
 dehydration 
 mood swings (including depression) 
 anxiety 
 difficulty sleeping 
 sensation disorders such as tingling, prickling or numbness 
 migraine 
 nerve root compression (including low back pain and leg pain) 
 vision disturbances 
 eye inflammation 
 inflammation of the eye lid and eye swelling 
 vertigo (feeling of dizziness or spinning) 
 sensation of heart beating rapidly 
 high blood pressure 
 flushing 
 haematoma (collection of blood outside of blood vessels) 
 cough 
 asthma 
 shortness of breath 
 gastrointestinal bleeding 
 dyspepsia (indigestion, bloating, heart burn) 
 acid reflux disease 
 sicca syndrome (including dry eyes and dry mouth) 
 itching 
 itchy rash 
 bruising 
 inflammation of the skin (such as eczema) 
 breaking of finger nails and toe nails 
 increased sweating 
 hair loss 
 new onset or worsening of psoriasis 
 muscle spasms 



522 

 blood in urine 
 kidney problems 
 chest pain 
 oedema (swelling) 
 fever 
 reduction in blood platelets which increases risk of bleeding or bruising 
 impaired healing 
 
Uncommon (may affect up to 1 in 100 people)   
 
 opportunistic infections (which include tuberculosis and other infections that occur when resistance 

to disease is lowered) 
 neurological infections (including viral meningitis) 
 eye infections 
 bacterial infections 
 diverticulitis (inflammation and infection of the large intestine) 
 cancer 
 cancer that affects the lymph system 
 melanoma 
 immune disorders that could affect the lungs, skin and lymph nodes (most commonly presenting as 

sarcoidosis) 
 vasculitis (inflammation of blood vessels) 
 tremor (shaking) 
 neuropathy (disorder of the nerves) 
 stroke 
 hearing loss, buzzing 
 sensation of heart beating irregularly such as skipped beats 
 heart problems that can cause shortness of breath or ankle swelling 
 heart attack 
 a sac in the wall of a major artery, inflammation and clot of a vein, blockage of a blood vessel 
 lung diseases causing shortness of breath (including inflammation) 
 pulmonary embolism (blockage in an artery of the lung) 
 pleural effusion (abnormal collection of fluid in the pleural space) 
 inflammation of the pancreas which causes severe pain in the abdomen and back 
 difficulty in swallowing 
 facial oedema (swelling of the face) 
 gallbladder inflammation, gallbladder stones 
 fatty liver 
 night sweats 
 scar 
 abnormal muscle breakdown 
 systemic lupus erythematosus (including inflammation of skin, heart, lung, joints and other organ 

systems) 
 sleep interruptions 
 impotence 
 inflammations 
 
Rare (may affect up to 1 in 1,000 people) 
 
 leukaemia (cancer affecting the blood and bone marrow) 



523 

 severe allergic reaction with shock 
 multiple sclerosis 
 nerve disorders (such as eye nerve inflammation and Guillain-Barré syndrome that may cause 

muscle weakness, abnormal sensations, tingling in the arms and upper body) 
 heart stops pumping 
 pulmonary fibrosis (scarring of the lung) 
 intestinal perforation (hole in the intestine) 
 hepatitis 
 reactivation of hepatitis B 
 autoimmune hepatitis (inflammation of the liver caused by the body's own immune system) 
 cutaneous vasculitis (inflammation of blood vessels in the skin) 
 Stevens-Johnson syndrome (early symptoms include malaise, fever, headache and rash) 
 facial oedema (swelling of the face) associated with allergic reactions 
 erythema multiforme (inflammatory skin rash) 
 lupus-like syndrome 
 angioedema (localized swelling of the skin) 
 lichenoid skin reaction (itchy reddish-purple skin rash) 
 
Not known (frequency cannot be estimated from the available data) 
 
 hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal) 
 Merkel cell carcinoma (a type of skin cancer) 
 Kaposi’s sarcoma, a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma 

most commonly appears as purple lesions on the skin 
 liver failure 
 worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle         

weakness) 
 
Some side effects observed with Humira may not have symptoms and may only be discovered through 
blood tests. These include: 
 
Very common (may affect more than 1 in 10 people) 
 
 low blood measurements for white blood cells 
 low blood measurements for red blood cells 
 increased lipids in the blood 
 elevated liver enzymes 
 
Common (may affect up to 1 in 10 people) 
 
 high blood measurements for white blood cells 
 low blood measurements for platelets 
 increased uric acid in the blood 
 abnormal blood measurements for sodium 
 low blood measurements for calcium 
 low blood measurements for phosphate 
 high blood sugar 
 high blood measurements for lactate dehydrogenase 
 autoantibodies present in the blood 
 low blood potassium 
 



524 

Uncommon (may affect up to 1 in 100 people)  
 
 elevated bilirubin measurement (liver blood test) 
 
Rare (may affect up to 1 in 1,000 people) 
 
 low blood measurements for white blood cells, red blood cells and platelet count 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects, you can help provide more information on the safety of this 
medicine. 
 
 
5. How to store Humira 
 
Keep this medicine out of the sight and reach of children.  
 
Do not use this medicine after the expiry date stated on the label/blister/carton after EXP.  
 
Store in a refrigerator (2C – 8C). Do not freeze.  
 
Keep the pre-filled pen in the outer carton in order to protect from light.   
 
Alternative Storage: 
 
When needed (for example, when you are travelling), a single Humira pre-filled pen may be stored at 
room temperature (up to 25°C) for a maximum period of 14 days – be sure to protect it from light. Once 
removed from the refrigerator for room temperature storage, the pen must be used within 14 days or 
discarded, even if it is returned to the refrigerator.   
 
You should record the date when the pen is first removed from refrigerator and the date after which it 
should be discarded. 
 
Do not throw away any medicines via wastewater or household waste. Ask your doctor or pharmacist how 
to throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Humira contains 
 
The active substance is adalimumab. 
The other ingredients are mannitol, polysorbate 80 and water for injections. 
 



525 

What the Humira pre-filled pen looks like and contents of the pack 
 
Humira 80 mg solution for injection in pre-filled pen is supplied as a sterile solution of 80 mg adalimumab 
dissolved in 0.8 ml solution. 
 
The Humira pre-filled pen is a single-use grey and plum-coloured pen which contains a glass syringe with 
Humira. There are two caps – one is grey and labelled ‘1’ and the other is plum and labelled ‘2’. There is a 
window on each side of the pen through which you can see the Humira solution inside the syringe. 
 
The Humira pre-filled pen is available in packs containing: 

 1 pre-filled pen for patient use with 2 alcohol pads (1 spare) 
 3 pre-filled pens for patient use with 4 alcohol pads (1 spare) 

 
Not all pack sizes may be marketed. 
 
 
Humira may be available as a vial, a pre-filled syringe and/or a pre-filled pen. 
 
Marketing Authorisation Holder 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
Manufacturer  
 
AbbVie Biotechnology GmbH 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
AbbVie SA 
Tél/Tel: +32 10  477811 

Lietuva 
AbbVie UAB  
Tel: +370 5 205 3023 

България 
АбВи ЕООД 
Тел.:+359 2 90 30 430 

Luxembourg/Luxemburg 
AbbVie SA 
Belgique/Belgien 
Tél/Tel: +32 10 477811

Česká republika 
AbbVie s.r.o.  
Tel: +420 233 098 111 

Magyarország 
AbbVie Kft. 
Tel.:+36 1 455 8600

Danmark 
AbbVie A/S 
Tlf: +45 72 30-20-28 

Malta 
V.J.Salomone Pharma Limited  
Tel: +356 22983201

Deutschland 
AbbVie Deutschland GmbH & Co. KG 
Tel: 00800 222843 33 (gebührenfrei) 
Tel: +49 (0) 611 / 1720-0

Nederland 
AbbVie B.V. 
Tel:  +31 (0)88 322 2843 



526 

Eesti 
AbbVie Biopharmaceuticals GmbH Eesti filiaal  
Tel: +372 623 1011 

Norge 
AbbVie AS 
Tlf: +47 67 81 80 00

Ελλάδα 
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. 
Τηλ: +30 214 4165 555 

Österreich 
AbbVie GmbH  
Tel: +43 1 20589-0 

España 
AbbVie Spain, S.L.U. 
Tel:  +34 91 384 09 10 

Polska 
AbbVie Polska Sp. z o.o. 
Tel.: +48 22 372 78 00 

France 
AbbVie 
Tél: +33 (0) 1 45 60 13 00 

Portugal 
AbbVie, Lda.  
Tel: +351 (0)21 1908400

Hrvatska  
AbbVie d.o.o. 
Tel + 385 (0)1 5625 501

România 
AbbVie S.R.L. 
Tel: +40 21 529 30 35

Ireland 
AbbVie Limited  
Tel: +353 (0)1 4287900

Slovenija 
AbbVie Biofarmacevtska družba d.o.o. 
Tel: +386 (1)32 08 060

Ísland 
Vistor hf. 
Tel: +354 535 7000 

Slovenská republika 
AbbVie s.r.o. 
Tel: +421 2 5050 0777

Italia 
AbbVie S.r.l.  
Tel: +39 06 928921 

Suomi/Finland 
AbbVie Oy  
Puh/Tel:  +358 (0)10 2411 200 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Τηλ.: +357 22 34 74 40

Sverige 
AbbVie AB 
Tel:  +46 (0)8 684 44 600

Latvija 
AbbVie SIA  
Tel: +371 67605000 

United Kingdom 
AbbVie Ltd  
Tel: +44 (0)1628 561090 

 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the 
local representative of the Marketing Authorisation Holder. 
 
 



527 

7.  Injecting Humira 
 

 The following instructions explain how to give yourself a subcutaneous injection of Humira using 
the pre-filled pen. First read all the instructions carefully and then follow them step by step.  
 

 You will be instructed by your doctor, nurse or pharmacist on the technique of self-injection.  
 

 Do not attempt to self-inject until you are sure that you understand how to prepare and give the 
injection.  
 

 After proper training, the injection can be given by yourself or given by another person, for 
example, a family member or friend. 
 

 Only use each pre-filled pen for one injection. 
 
Humira Pre-filled Pen 
 
   Grey Cap 1     White Needle Sleeve    White Arrow                          Plum-coloured Cap 2 

 
                              Needle           Inspection Window                    Plum Activator Button      
            
Do not use the pre-filled pen and call your doctor or pharmacist if the 
 

 liquid is cloudy, discoloured, or has flakes or particles in it 
 expiry (EXP) date has passed 
 liquid has been frozen or left in direct sunlight 
 pre-filled pen has been dropped or crushed 

 
Do not remove the caps until just before injection. Keep Humira out of the sight and reach of 
children. 
 

STEP 1 
 
Take Humira out of the refrigerator. 
 
Leave Humira at room temperature for 15 to 30 minutes before injecting. 
 

 Do not remove the Grey or Plum-coloured Caps while allowing Humira to reach room 
temperature 

 Do not warm Humira in any other way. For example, do not warm it in a microwave or in hot 
water 

 



528 

STEP 2  
 
               Pen 

 

                Pad 

 
Check expiry (EXP) date. Do not use the pre-filled pen if 
expiry (EXP) date has passed. 
 
Place the following on a clean, flat surface 
 

 1 single-use pre-filled pen and  
 1 alcohol pad 

 
Wash and dry your hands. 

STEP 3 
 
Injectable Areas 

     Injectable Areas 

 
Choose an injection site: 
 

 On the front of your thighs or 
 Your belly (abdomen) at least 5 cm from your belly 

button (navel) 
 At least 3 cm from your last injection site 

 
Wipe the injection site in a circular motion with the alcohol 
pad. 
 

 Do not inject through clothes 
 Do not inject into skin that is sore, bruised, red, 

hard, scarred, has stretch marks, or areas with 
psoriasis plaques 



529 

STEP 4 
 

 

 
Hold the pre-filled pen with the Grey Cap 1 pointing up.  
 
Check the inspection window. 
 

 It is normal to see 1 or more bubbles in the window 
 Make sure the liquid is clear and colourless 
 Do not use the pre-filled pen if the liquid is cloudy 

or has particles 
 Do not use the pre-filled pen if it has been dropped 

or crushed 

STEP 5  
 
Cap 1 

 
                                            Cap 2 

 
Pull the Grey Cap 1 straight off. Throw the cap away. Do 
not recap. 
 

 Check that the small black needle cover of the 
syringe has been removed with the cap 

 It is normal to see a few drops of liquid come out of 
the needle 

 
Pull the Plum-coloured Cap 2 straight off. Throw the cap 
away. Do not recap. 
 
The pre-filled pen is now ready to use. 
 
Turn the pre-filled pen so that the white arrow points toward 
the injection site.

STEP 6 
 

 
Squeeze the skin at your injection site with your other hand 
to make a raised area and hold it firmly until the injection is 
complete. 
 
Point the white arrow toward the injection site (thigh or 
abdomen). 
 
Place the white needle sleeve straight (90˚ angle) against the 
injection site. 
 
Hold the pre-filled pen so that you can see the inspection 
window. 
 
Do not press the plum activator button until you are ready to 
inject.



530 

STEP 7 
 
                             15 Seconds                  

 

 
Firmly push the pre-filled pen down against the injection 
site before starting the injection. 
Keep pushing down to prevent the pre-filled pen from 
moving away from the skin during the injection. 
 
Press the plum activator button and count slowly for 15 
seconds. 
 

 A loud “click” will signal the start of the injection 
 Keep pushing the pre-filled pen down firmly 

against the injection site until the injection is 
complete. 

 
The injection is complete when the yellow indicator has 
stopped moving. 

STEP 8 

  

 
When the injection is completed, slowly pull the pre-filled 
pen from the skin. The white needle sleeve will cover the 
needle tip. 

 A small amount of liquid on the injection site is 
normal 

 
If there are more than a few drops of liquid on the injection 
site, contact your doctor, nurse or pharmacist. 
 
After completing the injection, place a cotton ball or gauze 
pad on the skin over the injection site. 
 

 Do not rub 
 Slight bleeding at the injection site is normal 

STEP 9 
 
Throw away the used pre-filled pen in a special disposal container as instructed by your doctor, nurse 
or pharmacist. 
 

 Do not recycle or throw the pre-filled pen in the household waste 
 Always keep the pre-filled pen and the special disposal container out of the sight and reach of 

children 
 

The caps, alcohol pad, cotton ball or gauze pad, blister and packaging may be put in your household 
waste. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE ANDMANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVEUSE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET