Amsparity

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

 
 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Amsparity 20 mg solution for injection in pre-filled syringe 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each 0.4 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 to very light brown solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Juvenile idiopathic arthritis 
 
Polyarticular juvenile idiopathic arthritis 
 
Amsparity 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). Amsparity 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). Adalimumab has not been studied in 
patients aged less than 2 years. 
 
Enthesitis-related arthritis 
 
Amsparity 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 
 
Amsparity 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. 
 



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Paediatric Crohn's disease 
 
Amsparity 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 uveitis 
 
Amsparity 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 
 
Amsparity treatment should be initiated and supervised by specialist physicians experienced in the 
diagnosis and treatment of conditions for which Amsparity is indicated. Ophthalmologists are advised 
to consult with an appropriate specialist before initiation of treatment with Amsparity (see section 4.4). 
Patients treated with Amsparity should be given the patient reminder card. 
 
After proper training in injection technique, patients may self-inject with Amsparity if their physician 
determines that it is appropriate and with medical follow-up as necessary. 
 
During treatment with Amsparity, 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 Amsparity for patients with polyarticular juvenile idiopathic arthritis from 
2 years of age is based on body weight (Table 1). Amsparity is administered every other week via 
subcutaneous injection.  
 
Table 1. Amsparity 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 adalimumab in patients aged less than 2 years for this indication. 
 
Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs. 
 
Enthesitis-related arthritis 
 
The recommended dose of Amsparity for patients with enthesitis-related arthritis from 6 years of age is 
based on body weight (Table 2). Amsparity is administered every other week via subcutaneous 
injection.  



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Table 2. Amsparity 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 
 
Adalimumab has not been studied in patients with enthesitis-related arthritis aged less than 6 years. 
 
Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs. 
 
Paediatric plaque psoriasis 
The recommended Amsparity dose for patients with plaque psoriasis from 4 to 17 years of age is based 
on body weight (Table 3). Amsparity is administered via subcutaneous injection.  
 
Table 3. Amsparity 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 w ithin 
this time period. 
 
If retreatment with Amsparity is indicated, the above guidance on dose and treatment duration should 
be followed. 
 
The safety of adalimumab in paediatric patients with plaque psoriasis has been assessed for a mean of 
13 months. 
 
There is no relevant use of adalimumab in children aged less than 4 years for this indication. 
 
Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs. 
 
Paediatric Crohn's disease 
 
The recommended dose of Amsparity for patients with Crohn’s disease from 6 to 17 years of age is 
based on body weight (Table 4). Amsparity is administered via subcutaneous injection.  
 
Table 4. Amsparity 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 



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Patient 
weight 

Induction dose Maintenance dose 
starting at Week 4 

≥ 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 adalimumab in children aged less than 6 years for this indication. 
 
Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs. 
 
Paediatric uveitis 
 
The recommended dose of Amsparity for paediatric patients with uveitis from 2 years of age is based 
on body weight (Table 5). Amsparity is administered via subcutaneous injection.  
 
In paediatric uveitis, there is no experience in the treatment with adalimumab without concomitant 
treatment with methotrexate. 
 
Table 5. Amsparity 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 Amsparity 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 an Amsparity loading dose in children < 6 years of age (see 
section 5.2). 
 
There is no relevant use of adalimumab 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). 
 
Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs. 
 
Renal and/or hepatic impairment 
 
Adalimumab has not been studied in these patient populations. No dose recommendations can be 
made.  
 



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Method of administration 
 
Amsparity is administered by subcutaneous injection. Full instructions for use are provided in the 
package leaflet. 
 
Amsparity 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 the 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 Amsparity. Because the 
elimination of adalimumab may take up to four months, monitoring should be continued throughout 
this period. 
 
Treatment with Amsparity 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 
Amsparity should be considered prior to initiating therapy (see Other opportunistic infections). 
 
Patients who develop a new infection while undergoing treatment with Amsparity should be monitored 
closely and undergo a complete diagnostic evaluation. Administration of Amsparity 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 Amsparity 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 adalimumab. 
 
Other serious infections seen in clinical trials include pneumonia, pyelonephritis, septic arthritis and 
septicaemia. Hospitalisation or fatal outcomes associated with infections have been reported. 
 



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Tuberculosis 
 
Tuberculosis, including reactivation and new onset of tuberculosis, has been reported in patients 
receiving adalimumab. Reports included cases of pulmonary and extra-pulmonary (i.e. disseminated) 
tuberculosis. 
 
Before initiation of therapy with Amsparity, 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, Amsparity 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 Amsparity and in accordance with local 
recommendations. 
 
Use of anti-tuberculosis prophylaxis treatment should also be considered before the initiation of 
Amsparity 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 adalimumab. Some patients who have been successfully treated for active 
tuberculosis have redeveloped tuberculosis while being treated with adalimumab. 
 
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 Amsparity. 
 
Other opportunistic infections 
 
Opportunistic infections, including invasive fungal infections have been observed in patients receiving 
adalimumab. 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 Amsparity 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. 
 



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Hepatitis B reactivation 
 
Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including adalimumab, 
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 Amsparity. 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 Amsparity 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, Amsparity should be stopped and effective anti-viral therapy with 
appropriate supportive treatment should be initiated. 
 
Neurological events 
 
TNF-antagonists including adalimumab 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 Amsparity in patients with pre-existing or recent-onset central or peripheral nervous system 
demyelinating disorders; discontinuation of Amsparity 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 Amsparity therapy and regularly during treatment to assess for 
pre-existing or developing central demyelinating disorders. 
 
Allergic reactions 
 
Serious allergic reactions associated with adalimumab were rare during clinical trials. Non-serious 
allergic reactions associated with adalimumab were uncommon during clinical trials. Reports of 
serious allergic reactions including anaphylaxis have been received following adalimumab 
administration. If an anaphylactic reaction or other serious allergic reaction occurs, administration of 
Amsparity should be discontinued immediately and appropriate therapy initiated. 
 
Immunosuppression 
 
In a study of 64 patients with rheumatoid arthritis that were treated with adalimumab, 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 



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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 adalimumab 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 
adalimumab should be carefully considered. A risk for the development of hepatosplenic T-cell 
lymphoma in patients treated with Amsparity 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 adalimumab is continued following development of malignancy. Thus, additional 
caution should be exercised in considering adalimumab 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 Amsparity. 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 adalimumab. 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 Amsparity. Discontinuation of Amsparity 
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 adalimumab. 
 
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 adalimumab therapy. 
 
Patients on adalimumab 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. 



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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 adalimumab. Amsparity should be used with 
caution in patients with mild heart failure (NYHA class I/II). Amsparity is contraindicated in moderate 
to severe heart failure (see section 4.3). Treatment with Amsparity must be discontinued in patients 
who develop new or worsening symptoms of congestive heart failure. 
 
Autoimmune processes 
 
Treatment with Amsparity may result in the formation of autoimmune antibodies. The impact of 
long-term treatment with adalimumab on the development of autoimmune diseases is unknown. If a 
patient develops symptoms suggestive of a lupus-like syndrome following treatment with Amsparity 
and is positive for antibodies against double-stranded DNA, further treatment with Amsparity 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 adalimumab. The 
long half-life of adalimumab should be taken into consideration if a surgical procedure is planned. A 
patient who requires surgery while on Amsparity should be closely monitored for infections, and 
appropriate actions should be taken. There is limited safety experience in patients undergoing 
arthroplasty while receiving adalimumab. 
 
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 adalimumab does not worsen or cause 
strictures. 
 
Elderly 
 
The frequency of serious infections among adalimumab-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. 
 



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Excipient 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 
 
Adalimumab has been studied in rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and 
psoriatic arthritis patients taking adalimumab as monotherapy and those taking concomitant 
methotrexate. Antibody formation was lower when adalimumab was given together with methotrexate 
in comparison with use as monotherapy. Administration of adalimumab without methotrexate resulted 
in increased formation of antibodies, increased clearance and reduced efficacy of adalimumab (see 
section 5.1). 
 
The combination of Amsparity and anakinra is not recommended (see section 4.4 “Concurrent 
administration of biologic DMARDS or TNF-antagonists”). 
 
The combination of Amsparity 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 Amsparity treatment. 
 
Pregnancy 
 
A large number (approximately 2,100) of prospectively collected pregnancies exposed to adalimumab 
resulting in live birth with known outcomes, including more than 1,500 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-randomised 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 TNFα, 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 



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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, Amsparity can be used during breast-feeding. 
 
Fertility 
 
Preclinical data on fertility effects of adalimumab are not available. 
 
4.7 Effects on ability to drive and use machines 
 
Adalimumab may have a minor influence on the ability to drive and use machines. Vertigo and visual 
impairment may occur following administration of Amsparity (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Adalimumab 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 adalimumab 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 adalimumab 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 adalimumab. TNF-antagonists, such as adalimumab 
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 adalimumab. 
 
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. 
 



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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 
 

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 
 



14 

System organ class Frequency Adverse reaction 
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 
 

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 
 



15 

System organ class Frequency Adverse reaction 
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, 
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 
 



16 

System organ class Frequency Adverse reaction 
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 
 

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 



17 

System organ class Frequency Adverse reaction 
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 adalimumab every other week was consistent 
with the known safety profile of adalimumab. 
 
Description of selected adverse reactions 
 
Injection site reactions 
 
In the pivotal controlled trials in adults and children, 12.9% of patients treated with adalimumab 
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 adalimumab-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 adalimumab after the infection resolved. 
 
The incidence of serious infections was 0.04 per patient year in adalimumab-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 adalimumab, 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 adalimumab 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 adalimumab 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 an adalimumab 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 an 
adalimumab trial in paediatric patients with uveitis. 
 
During the controlled portions of pivotal adalimumab 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 



18 

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 adalimumab-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 
adalimumab 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 adalimumab-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 adalimumab-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 adalimumab-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 adalimumab 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 adalimumab 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 adalimumab 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 adalimumab-treated patients and 1.6% of control-treated patients. 
 
In controlled Phase 3 trials of adalimumab 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 adalimumab-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 adalimumab in patients with polyarticular juvenile idiopathic arthritis 
who were 2 to < 4 years. 
 
In controlled Phase 3 trials of adalimumab 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 
adalimumab-treated patients and 0.9% of controlled-treated patients. 
 
In the Phase 3 trial of adalimumab in patients with paediatric Crohn’s disease which evaluated efficacy 
and safety of two body weight adjusted maintenance dose regimens following body weight adjusted 



19 

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 adalimumab 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 
adalimumab-treated patients and 1.8% of control-treated patients. 
 
No ALT elevations ≥ 3 x ULN occurred in the Phase 3 trial of adalimumab in paediatric patients with 
plaque psoriasis. 
 
In controlled trials of adalimumab (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 adalimumab-treated and control-treated patients, respectively, ALT 
elevations ≥ 3 x ULN occurred in 2.4% of adalimumab-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 adalimumab and azathioprine/6-mercaptopurine compared 
with adalimumab 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 
 
Amsparity is a biosimilar medicinal product. Detailed information is available on the website of the 
European Medicines Agency http://www.ema.europa.eu. 
 
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. 
 

http://www.ema.europa.eu/
http://www.ema.europa.eu/


20 

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 adalimumab, 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 adalimumab administration. Patients treated with adalimumab 
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 
adalimumab. 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 
 
Juvenile idiopathic arthritis (JIA) 
 
Polyarticular juvenile idiopathic arthritis (pJIA) 
 
The safety and efficacy of adalimumab 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 adalimumab 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 adalimumab 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 7. 
 
Table 7. 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 adalimumab 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. 
 



21 

Table 8. 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 Adalimumab / 

MTX 
(N = 38) 

Placebo / MTX 
(N = 37) 

Adalimumab 
(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 adalimumab 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 adalimumab and MTX compared to adalimumab alone. Taking these results into 
consideration, adalimumab 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 adalimumab 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 adalimumab 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, PedACR 30 response was 93.5% and 90.0%, respectively, using the 
observed data approach. The proportions of subjects with PedACR 50/70/90 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 adalimumab throughout this 
time period. Overall, 20 subjects were treated for 60 weeks or longer. 
 
Enthesitis-related arthritis 
 
The safety and efficacy of adalimumab 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 adalimumab 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 adalimumab 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 
adalimumab group compared to -11.6% (median percent change -50.0%) in patients in the placebo 



22 

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 adalimumab 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. 
 
Adults with rheumatoid arthritis 
 
Adalimumab was evaluated in over 3,000 patients in all rheumatoid arthritis clinical trials. The 
efficacy and safety of adalimumab 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 adalimumab 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 adalimumab 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 adalimumab 
every week for 52 weeks. The third group received 40 mg of adalimumab 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 adalimumab/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 
adalimumab 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 
adalimumab 40 mg every other week/methotrexate combination therapy, adalimumab 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 adalimumab 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. 
 



23 

ACR response 
 
The percent of adalimumab-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 9. 
 
Table 9. ACR responses in placebo-controlled trials (percent of patients) 
 
Response RA study Ia** RA study IIa** RA study IIIa** 

Placebo/ 
MTXc 
n = 60 

Adalimumabb
/ MTXc 
n = 63 

Placebo 
n = 110 

Adalimumabb 
n = 113 

Placebo/ 
MTXc 

n = 200 

Adalimumabb
/ 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 adalimumab administered every other week 
c  MTX = methotrexate 
** p < 0.01, adalimumab 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 adalimumab 
40 mg every other week, 114 patients continued on adalimumab 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 adalimumab 
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 adalimumab 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, adalimumab-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 adalimumab and methotrexate led to faster and significantly greater ACR responses than 
methotrexate monotherapy and adalimumab monotherapy at Week 52 and responses were sustained at 
Week 104 (see Table 10). 
 
Table 10. ACR responses in RA study V (percent of patients) 
 

Response MTX n = 257 
Adalimumab 

n = 274 
Adalimumab/MTX 

n = 268 p-value
a 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 



24 

Response MTX n = 257 
Adalimumab 

n = 274 
Adalimumab/MTX 

n = 268 p-value
a p-valueb p-valuec 

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 adalimumab/methotrexate 
combination therapy using the Mann-Whitney U test.  

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

c  p-value is from the pairwise comparison of adalimumab 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 adalimumab 40 mg every other week, 
170 patients continued on adalimumab 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 adalimumab/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 adalimumab monotherapy. adalimumab/methotrexate 
combination therapy was clinically and statistically superior to methotrexate (p < 0.001) and 
adalimumab 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 randomised to adalimumab monotherapy or 
adalimumab/methotrexate combination therapy who entered the open-label extension study, 
171 subjects completed 10 years of adalimumab treatment. Among those, 109 subjects (63.7%) were 
reported to be in remission at 10 years. 
 
Radiographic response 
 
In RA study III, where adalimumab-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. Adalimumab/methotrexate patients demonstrated significantly less radiographic 
progression than patients receiving methotrexate alone at 6 and 12 months (see Table 11). 
 
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 adalimumab 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 adalimumab 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 11. Radiographic mean changes over 12 months in RA study III 
 
 Placebo/ 

MTXa 
Adalimumab/MTX 
40 mg every other 

week 

Placebo/MTX- 
Adalimumab/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 



25 

 Placebo/ 
MTXa 

Adalimumab/MTX 
40 mg every other 

week 

Placebo/MTX- 
Adalimumab/MTX 
(95% confidence 

intervalb) 

p-value 

JSNd score 1.0 0.1 0.9 (0.3, 1.4) 0.002 
a  methotrexate 
b  95% confidence intervals for the differences in change scores between methotrexate and adalimumab. 
c  Based on rank analysis 
d  Joint Space Narrowing 
 
In RA study V, structural joint damage was assessed radiographically and expressed as change in 
modified Total Sharp Score (see Table 12). 
 
Table 12. Radiographic mean changes at Week 52 in RA study V 
 
 MTX 

n = 257 
(95% 

confidence 
interval) 

Adalimumab 
n = 274 
(95% 

confidence 
interval) 

Adalimumab/
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 adalimumab/methotrexate 

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

combination therapy using the Mann-Whitney U test. 
c  p-value is from the pairwise comparison of adalimumab 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 
adalimumab/methotrexate combination therapy (63.8% and 61.2%, respectively) compared to 
methotrexate monotherapy (37.4% and 33.5% respectively, p < 0.001) and adalimumab 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 randomised to methotrexate 
monotherapy, adalimumab monotherapy and adalimumab/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 
adalimumab 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 
adalimumab 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). 



26 

 
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 adalimumab/methotrexate combination therapy versus 
methotrexate monotherapy and adalimumab 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. 
 
Paediatric plaque psoriasis 
 
The efficacy of adalimumab 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 adalimumab 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 
adalimumab 0.8 mg/kg had positive efficacy responses (e.g. PASI 75) than those randomised to 
0.4 mg/kg eow or MTX. 
 
Table 13. Paediatric plaque psoriasis efficacy results at 16 weeks 
 

 MTXa 
N = 37 

Adalimumab 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, adalimumab 0.8 mg/kg versus MTX 
c  P = 0.083, adalimumab 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. 
 
Adult plaque psoriasis 
 
The safety and efficacy of adalimumab 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 adalimumab 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 adalimumab at an initial dose of 80 mg followed by 40 mg every other 



27 

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 adalimumab 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 adalimumab 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 adalimumab 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 adalimumab followed by 40 mg every other week (starting one week after the initial dose) for 
16 weeks. There are no data available comparing adalimumab 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 adalimumab 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 14 and 15). 
 
Table 14. Ps study I (REVEAL) efficacy results at 16 weeks 

 
 Placebo 

N = 398 
n (%) 

Adalimumab 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 PASI 75 response was calculated as centre-adjusted rate 
b  p < 0.001, adalimumab vs. placebo 
 
Table 15. Ps study II (CHAMPION) efficacy results at 16 weeks 
 
 Placebo  

N = 53  
n (%) 

MTX  
N = 110  
n (%) 

Adalimumab 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 adalimumab vs. placebo 
b  p < 0.001 adalimumab vs. methotrexate 
c  p < 0.01 adalimumab vs. placebo 
d  p < 0.05 adalimumab 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 adalimumab, 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. 
 



28 

A total of 233 PASI 75 responders at Week 16 and Week 33 received continuous adalimumab therapy 
for 52 weeks in Psoriasis Study I, and continued adalimumab 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 adalimumab 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 adalimumab 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 adalimumab 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 adalimumab versus placebo in 217 adult patients 
with moderate to severe nail psoriasis. Patients received an initial dose of 80 mg adalimumab followed 
by 40 mg every other week (starting one week after the initial dose) or placebo for 26 weeks followed 
by open-label adalimumab 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 16). 
Adalimumab 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 16. 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 

Adalimumab 
40 mg eow 

N = 109 

Placebo 
N = 108 

Adalimumab 
40 mg eow 

N = 109 

Adalimumab 
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 



29 

Endpoint Week 16 
Placebo-controlled 

Week 26 
Placebo-controlled 

Week 52 
Open-label 

Placebo 
N = 108 

Adalimumab 
40 mg eow 

N = 109 

Placebo 
N = 108 

Adalimumab 
40 mg eow 

N = 109 

Adalimumab 
40 mg eow 

N = 80 
Percent Change in 
Total Fingernail 
NAPSI (%) 

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

a  p < 0.001, adalimumab vs. placebo 
 
Adalimumab treated patients showed statistically significant improvements at Week 26 compared with 
placebo in the DLQI. 
 
Paediatric Crohn’s disease 
 
Adalimumab 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 17. 

 
Table 17. 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 18. Rates of discontinuation of corticosteroids or 
immunomodulators are presented in Table 19. 
 
Table 18. 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. 
 



30 

Table 19. 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. 
 
Adult Crohn’s disease 
 
The safety and efficacy of adalimumab were assessed in over 1,500 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 naïve patients were 
randomised to one of four treatment groups; placebo at Weeks 0 and 2, 160 mg adalimumab 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 adalimumab 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 20. 
 



31 

Table 20. Induction of clinical remission and response (percent of patients) 
 

 CD Study I: Infliximab naïve patients CD Study II: Infliximab 
experienced patients 

 Placebo 
N = 74 

Adalimumab 
80/40 mg 

N = 75 

Adalimumab 
160/80 mg 

N = 76 

Placebo 
N = 166 

Adalimumab 
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 adalimumab 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 21. 
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 21. Maintenance of clinical remission and response (percent of patients) 

 
 Placebo 40 mg Adalimumab every other week 

40 mg Adalimumab 
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 adalimumab versus placebo pairwise comparisons of proportions  
** p < 0.02 for adalimumab 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 adalimumab 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. 
 



32 

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 adalimumab 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. 
 
Paediatric uveitis 
 
The safety and efficacy of adalimumab was assessed in a randomised, double-masked, controlled study 
of 90 paediatric patients from 2 to < 18 years of age with active JIA-associated non-infectious 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 1, 
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]). 
 



33 

Figure 1. Kaplan-Meier curves summarizing time to treatment failure in the paediatric uveitis 
study 

 
Note: P = Placebo (Number at Risk); H = Adalimumab (Number at Risk). 
 
Adult uveitis 
 
The safety and efficacy of adalimumab 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 
adalimumab 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). 
 



34 

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 adalimumab. 
 
Clinical response 
 
Results from both studies demonstrated statistically significant reduction of the risk of treatment 
failure in patients treated with adalimumab versus patients receiving placebo (see Table 22). Both 
studies demonstrated an early and sustained effect of adalimumab on the treatment failure rate versus 
placebo (see Figure 2). 
 
Table 22. 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 Valueb 

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) 

 
 



35 

 
Note: P# = Placebo (Number of Events/Number at Risk); A# = Adalimumab (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. Adalimumab 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 adalimumab for colour vision in Study UV I and for colour 
vision, peripheral vision and near vision in Study UV II. 
 
Immunogenicity 
 
Anti-adalimumab antibodies may develop during adalimumab treatment. 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. 
 



36 

Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of the studies with 
the reference medicinal product containing adalimumab in one or more subsets of the paediatric 
population in ulcerative colitis (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption and distribution 
 
Following the administration of 24 mg/m2 (up to a 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 (up to a 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 (up to a 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 µg/ml for patients ≥ 40 kg 
(160/80 mg) and 10.6 ± 6.1 µg/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 µg/ml for the Standard Dose group and 3.5 ± 2.2 µg/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). 



37 

 
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. 
 
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 µg/ml 
(without concomitant methotrexate) and 8 to 9 µg/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 patients with Crohn’s disease, the loading dose of 80 mg adalimumab on Week 0 followed by 
40 mg adalimumab on Week 2 achieves serum adalimumab trough concentrations of approximately 
5.5 µg/ml during the induction period. A loading dose of 160 mg adalimumab on Week 0 followed by 
80 mg adalimumab on Week 2 achieves serum adalimumab trough concentrations of approximately 
12 µg/ml during the induction period. Mean steady-state trough levels of approximately 7 µg/ml were 
observed in Crohn’s disease patients who received a maintenance dose of 40 mg adalimumab 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 µg/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 
 
Adalimumab has not been studied in patients with hepatic or renal impairment. 
 



38 

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 
cynomologous 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 
 
L-Histidine 
L-Histidine hydrochloride monohydrate 
Sucrose 
Edetate Disodium Dihydrate  
L-Methionine 
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 
 
3 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 Amsparity pre-filled syringe may be stored at temperatures up to a maximum of 30°C for a 
period of up to 30 days. The syringe must be protected from light, and discarded if not used within the 
30-day period. 
 
6.5 Nature and contents of container 
 
Amsparity 20 mg solution for injection in single-use pre-filled syringe (type I glass) with a plunger 
stopper (chlorobutyl rubber) and a needle with a needle shield (thermoplastic elastomer). 
 
Packs of: 
• 2 pre-filled syringes (0.4 ml sterile solution) with 2 alcohol pads, each pre-filled syringe is 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. 
 



39 

 
7. MARKETING AUTHORISATION HOLDER 
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBER 
 
EU/1/19/1415/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
<Date of first authorisation: {DD month YYYY}> 
 
 
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. 
 

http://www.ema.europa.eu/
http://www.ema.europa.eu/


40 

This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Amsparity 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 to very light brown solution.  
 
 
4. CLINICAL PARTICULARS  
 
4.1 Therapeutic indications  
 
Juvenile idiopathic arthritis 
 
Polyarticular juvenile idiopathic arthritis 
 
Amsparity 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). Amsparity 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). Adalimumab has not been studied in 
patients aged less than 2 years. 
 
Enthesitis-related arthritis 
 
Amsparity 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 
 
Amsparity 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 
 
Amsparity 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 



41 

primary nutrition therapy and a corticosteroid and/or an immunomodulator, or who are intolerant to or 
have contraindications for such therapies.  
 
Adolescent hidradenitis suppurativa 
 
Amsparity is indicated for the treatment of active moderate to severe hidradenitis suppurativa (HS) 
(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 uveitis 
 
Amsparity 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 
 
Amsparity treatment should be initiated and supervised by specialist physicians experienced in the 
diagnosis and treatment of conditions for which Amsparity is indicated. Ophthalmologists are advised 
to consult with an appropriate specialist before initiation of treatment with Amsparity (see section 4.4). 
Patients treated with Amsparity should be given the patient reminder card. 
 
After proper training in injection technique, patients may self-inject with Amsparity if their physician 
determines that it is appropriate and with medical follow-up as necessary.  
 
During treatment with Amsparity, 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 Amsparity for patients with polyarticular juvenile idiopathic arthritis from 
2 years of age is based on body weight (Table 1). Amsparity is administered every other week via 
subcutaneous injection.  
 
Table 1. Amsparity 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 adalimumab in patients aged less than 2 years for this indication. 
 
Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs.  
 



42 

Enthesitis-related arthritis  
 
The recommended dose of Amsparity for patients with enthesitis-related arthritis from 6 years of age is 
based on body weight (Table 2). Amsparity is administered every other week via subcutaneous 
injection.  
 
Table 2. Amsparity 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 
 
Adalimumab has not been studied in patients with enthesitis-related arthritis aged less than 6 years. 
 
Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs.  
 
Paediatric plaque psoriasis 
 
The recommended Amsparity dose for patients with plaque psoriasis from 4 to 17 years of age is based 
on body weight (Table 3). Amsparity is administered via subcutaneous injection.  
 
Table 3. Amsparity 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 Amsparity is indicated, the above guidance on dose and treatment duration should 
be followed. 
 
The safety of adalimumab in paediatric patients with plaque psoriasis has been assessed for a mean of 
13 months. 
 
There is no relevant use of adalimumab in children aged less than 4 years for this indication. 
 
Amsparity 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 adalimumab in adolescent patients with HS.  
 
The posology of adalimumab in these patients has been determined from pharmacokinetic modelling 
and simulation (see section 5.2). 
 
The recommended Amsparity 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 Amsparity 40 mg every other week, an increase in 
dosage to 40 mg every week or 80 mg every other week may be considered. 
 



43 

Antibiotics may be continued during treatment with Amsparity 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 Amsparity. 
 
Continued therapy beyond 12 weeks should be carefully reconsidered in a patient with no 
improvement within this time period. 
 
Should treatment be interrupted, Amsparity 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 adalimumab in children aged less than 12 years in this indication.  
 
Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs. 
 
Paediatric Crohn’s disease 
 
The recommended dose of Amsparity for patients with Crohn’s disease from 6 to 17 years of age is 
based on body weight (Table 4). Amsparity is administered via subcutaneous injection.  
 
Table 4. Amsparity 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 adalimumab in children aged less than 6 years for this indication.  
 
Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs. 
 
Paediatric uveitis 
 
The recommended dose of Amsparity for paediatric patients with uveitis from 2 years of age is based 
on body weight (Table 5). Amsparity is administered via subcutaneous injection.  
 
In paediatric uveitis, there is no experience in the treatment with adalimumab without concomitant 
treatment with methotrexate. 



44 

 
Table 5. Amsparity 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 Amsparity 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 an Amsparity loading dose in children < 6 years of age (see 
section 5.2). 
 
There is no relevant use of adalimumab 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). 
 
Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs. 
 
Renal and/or hepatic impairment 
 
Adalimumab has not been studied in these patient populations. No dose recommendations can be 
made.  
 
Method of administration 
 
Amsparity is administered by subcutaneous injection. Full instructions for use are provided in the 
package leaflet.  
 
Amsparity 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 the 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 Amsparity. Because the 
elimination of adalimumab may take up to four months, monitoring should be continued throughout 
this period. 



45 

 
Treatment with Amsparity 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 
Amsparity should be considered prior to initiating therapy (see Other opportunistic infections). 
 
Patients who develop a new infection while undergoing treatment with Amsparity should be monitored 
closely and undergo a complete diagnostic evaluation. Administration of Amsparity 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 Amsparity 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 adalimumab. 
 
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 adalimumab. Reports included cases of pulmonary and extra-pulmonary (i.e. disseminated) 
tuberculosis. 
 
Before initiation of therapy with Amsparity, 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, Amsparity 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 Amsparity, and in accordance with local 
recommendations.  
 
Use of anti-tuberculosis prophylaxis treatment should also be considered before the initiation of 
Amsparity 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. 
 



46 

Despite prophylactic treatment for tuberculosis, cases of reactivated tuberculosis have occurred in 
patients treated with adalimumab. Some patients who have been successfully treated for active 
tuberculosis have redeveloped tuberculosis while being treated with adalimumab.  
 
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 Amsparity.  
 
Other opportunistic infections 
 
Opportunistic infections, including invasive fungal infections have been observed in patients receiving 
adalimumab. 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 Amsparity 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 adalimumab, 
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 Amsparity. 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 Amsparity 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, Amsparity should be stopped and effective anti-viral therapy with 
appropriate supportive treatment should be initiated.  
 
Neurological events 
 
TNF-antagonists including adalimumab 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 Amsparity in patients with pre-existing or recent-onset central or peripheral nervous system 
demyelinating disorders; discontinuation of Amsparity 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 Amsparity therapy and regularly during treatment to assess for 
pre-existing or developing central demyelinating disorders. 
 
Allergic reactions 
 
Serious allergic reactions associated with adalimumab were rare during clinical trials. Non-serious 
allergic reactions associated with adalimumab were uncommon during clinical trials. Reports of 
serious allergic reactions including anaphylaxis have been received following adalimumab 
administration. If an anaphylactic reaction or other serious allergic reaction occurs, administration of 
Amsparity should be discontinued immediately and appropriate therapy initiated.  



47 

 
Immunosuppression 
 
In a study of 64 patients with rheumatoid arthritis that were treated with adalimumab, 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 adalimumab 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 
adalimumab should be carefully considered. A risk for the development of hepatosplenic T-cell 
lymphoma in patients treated with Amsparity 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 adalimumab is continued following development of malignancy. Thus, additional 
caution should be exercised in considering adalimumab 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 Amsparity. 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.  
 



48 

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 adalimumab. 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 Amsparity. Discontinuation of Amsparity 
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 adalimumab.  
 
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 adalimumab therapy.  
 
Patients on adalimumab 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 adalimumab. Amsparity should be used with 
caution in patients with mild heart failure (NYHA class I/II). Amsparity is contraindicated in moderate 
to severe heart failure (see section 4.3). Treatment with Amsparity must be discontinued in patients 
who develop new or worsening symptoms of congestive heart failure. 
 
Autoimmune processes 
 
Treatment with Amsparity may result in the formation of autoimmune antibodies. The impact of 
long-term treatment with adalimumab on the development of autoimmune diseases is unknown. If a 
patient develops symptoms suggestive of a lupus-like syndrome following treatment with Amsparity 
and is positive for antibodies against double-stranded DNA, further treatment with Amsparity 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 adalimumab. The 
long half-life of adalimumab should be taken into consideration if a surgical procedure is planned. A 



49 

patient who requires surgery while on Amsparity should be closely monitored for infections, and 
appropriate actions should be taken. There is limited safety experience in patients undergoing 
arthroplasty while receiving adalimumab.  
 
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 adalimumab does not worsen or cause 
strictures.  
 
Elderly 
 
The frequency of serious infections among adalimumab-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.  
 
Excipient 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 
 
Adalimumab has been studied in rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and 
psoriatic arthritis patients taking adalimumab as monotherapy and those taking concomitant 
methotrexate. Antibody formation was lower when adalimumab was given together with methotrexate 
in comparison with use as monotherapy. Administration of adalimumab without methotrexate resulted 
in increased formation of antibodies, increased clearance and reduced efficacy of adalimumab (see 
section 5.1).  
 
The combination of Amsparity and anakinra is not recommended (see section 4.4 “Concurrent 
administration of biologic DMARDS or TNF-antagonists”).  
 
The combination of Amsparity 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 Amsparity treatment. 
 
Pregnancy 
 
A large number (approximately 2,100) of prospectively collected pregnancies exposed to adalimumab 
resulting in live birth with known outcomes, including more than 1,500 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 



50 

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-randomised 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 TNFα, 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, Amsparity can be used during breast-feeding. 
 
Fertility 
 
Preclinical data on fertility effects of adalimumab are not available. 
 
4.7 Effects on ability to drive and use machines  
 
Adalimumab may have a minor influence on the ability to drive and use machines. Vertigo and visual 
impairment may occur following administration of Amsparity (see section 4.8).  
 
4.8 Undesirable effects  
 
Summary of the safety profile 
 
Adalimumab 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 adalimumab 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 adalimumab and 5.4% for control 
treated patients.  
 



51 

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 adalimumab. TNF-antagonists, such as adalimumab 
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 adalimumab.  
 
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 
 



52 

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 
 

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 
 



53 

System organ class Frequency Adverse reaction 
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, 
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 
 



54 

System organ class Frequency Adverse reaction 
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 
 

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 
 



55 

System organ class Frequency Adverse reaction 
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 
1 including spontaneous reporting data  
 
Hidradenitis suppurativa 
 
The safety profile for patients with HS treated with adalimumab weekly was consistent with the known 
safety profile of adalimumab. 
 
Uveitis 
 
The safety profile for patients with uveitis treated with adalimumab every other week was consistent 
with the known safety profile of adalimumab. 
 
Description of selected adverse reactions 
 
Injection site reactions 
 
In the pivotal controlled trials in adults and children, 12.9% of patients treated with adalimumab 
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. 
 



56 

Infections  
 
In the pivotal controlled trials in adults and children, the rate of infection was 1.51 per patient year in 
the adalimumab-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 adalimumab after the infection resolved. 
 
The incidence of serious infections was 0.04 per patient year in adalimumab-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 adalimumab, 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 adalimumab 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 adalimumab 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 an adalimumab 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 an 
adalimumab trial in paediatric patients with uveitis. 
 
During the controlled portions of pivotal adalimumab 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 adalimumab-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 
adalimumab 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 adalimumab-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 adalimumab-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 adalimumab-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).  
 



57 

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 adalimumab 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 adalimumab 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 adalimumab 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 adalimumab-treated patients and 1.6% of control-treated patients.  
 
In controlled Phase 3 trials of adalimumab 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 adalimumab-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 adalimumab in patients with polyarticular juvenile idiopathic arthritis 
who were 2 to < 4 years.  
 
In controlled Phase 3 trials of adalimumab 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 
adalimumab-treated patients and 0.9% of controlled-treated patients.  
 
In the Phase 3 trial of adalimumab 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 adalimumab 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 
adalimumab-treated patients and 1.8% of control-treated patients.  
 
No ALT elevations ≥ 3 x ULN occurred in the Phase 3 trial of adalimumab in paediatric patients with 
plaque psoriasis.  
 
In controlled trials of adalimumab (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 
adalimumab-treated patients and 0.6% of control-treated patients.  
 
In controlled trials of adalimumab (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 adalimumab-treated and control-treated patients, respectively, ALT 
elevations ≥ 3 x ULN occurred in 2.4% of adalimumab-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.  



58 

 
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 adalimumab and azathioprine/6-mercaptopurine compared 
with adalimumab 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 
 
Amsparity is a biosimilar medicinal product. Detailed information is available on the website of the 
European Medicines Agency http://www.ema.europa.eu. 
 
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 adalimumab, 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 adalimumab administration. Patients treated with adalimumab 
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 
adalimumab. 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.  
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/
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59 

Clinical efficacy and safety 
 
Juvenile idiopathic arthritis (JIA)  
 
Polyarticular juvenile idiopathic arthritis (pJIA) 
 
The safety and efficacy of adalimumab 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 adalimumab 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 adalimumab 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 7.  
 
Table 7. 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 adalimumab 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 8. 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 Adalimumab / 

MTX 
(N = 38) 

Placebo / MTX 
(N = 37) 

Adalimumab 
(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 
 



60 

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 adalimumab 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 adalimumab and MTX compared to adalimumab alone. Taking these results into 
consideration, adalimumab 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 adalimumab 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 adalimumab 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, PedACR 30 response was 93.5% and 90.0%, respectively, using the 
observed data approach. The proportions of subjects with PedACR 50/70/90 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 adalimumab throughout this 
time period. Overall, 20 subjects were treated for 60 weeks or longer.  
 
Enthesitis-related arthritis  
 
The safety and efficacy of adalimumab 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 adalimumab 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 adalimumab 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 
adalimumab 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 adalimumab 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.  
 
Adults with rheumatoid arthritis  
 
Adalimumab was evaluated in over 3,000 patients in all rheumatoid arthritis clinical trials. The 
efficacy and safety of adalimumab 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 adalimumab or placebo were given every other week for 24 weeks.  
 



61 

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 adalimumab 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 adalimumab 
every week for 52 weeks. The third group received 40 mg of adalimumab 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 adalimumab/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 
adalimumab 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 
adalimumab 40 mg every other week/methotrexate combination therapy, adalimumab 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 adalimumab 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 adalimumab-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 9.  
 
Table 9. ACR responses in placebo-controlled trials (percent of patients) 
 
Response RA Study Ia** RA Study IIa** RA Study IIIa** 

Placebo/ 
MTXc 
n = 60 

Adalimumabb
/ MTXc 
n = 63 

Placebo 
n = 110 

Adalimumabb 
n = 113 

Placebo/ 
MTXc 

n = 200 

Adalimumabb
/ 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% 



62 

Response RA Study Ia** RA Study IIa** RA Study IIIa** 
Placebo/ 

MTXc 
n = 60 

Adalimumabb
/ MTXc 
n = 63 

Placebo 
n = 110 

Adalimumabb 
n = 113 

Placebo/ 
MTXc 

n = 200 

Adalimumabb
/ MTXc 
n = 207 

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 adalimumab administered every other week 
c  MTX = methotrexate 
** p < 0.01, adalimumab 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 adalimumab 
40 mg every other week, 114 patients continued on adalimumab 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 adalimumab 
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 adalimumab 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, adalimumab-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 adalimumab and methotrexate led to faster and significantly greater ACR responses than 
methotrexate monotherapy and adalimumab monotherapy at Week 52 and responses were sustained at 
Week 104 (see Table 10).  
 
Table 10. ACR responses in RA study V (percent of patients) 
 

Response MTX n = 257 
Adalimumab 

n = 274 
Adalimumab/MTX 

n = 268 p-value
a 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 adalimumab/methotrexate 
combination therapy using the Mann-Whitney U test.  

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

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

 



63 

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 adalimumab 40 mg every other week, 
170 patients continued on adalimumab 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 adalimumab/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 adalimumab monotherapy. adalimumab/methotrexate 
combination therapy was clinically and statistically superior to methotrexate (p < 0.001) and 
adalimumab 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 randomised to adalimumab monotherapy or 
adalimumab/methotrexate combination therapy who entered the open-label extension study, 
171 subjects completed 10 years of adalimumab treatment. Among those, 109 subjects (63.7%) were 
reported to be in remission at 10 years.  
 
Radiographic response  
 
In RA study III, where adalimumab-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. Adalimumab/methotrexate patients demonstrated significantly less radiographic 
progression than patients receiving methotrexate alone at 6 and 12 months (see Table 11).  
 
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 adalimumab 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 adalimumab 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 11. Radiographic mean changes over 12 months in RA study III 
 
 Placebo/ 

MTXa 
Adalimumab/MTX 
40 mg every other 

week 

Placebo/MTX- 
Adalimumab/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 
a  methotrexate 
b  95% confidence intervals for the differences in change scores between methotrexate and adalimumab. 
c  Based on rank analysis 
d  Joint Space Narrowing 
 
In RA study V, structural joint damage was assessed radiographically and expressed as change in 
modified Total Sharp Score (see Table 12).  
 



64 

Table 12. Radiographic mean changes at Week 52 in RA study V 
 
 MTX 

n = 257 
(95% 

confidence 
interval) 

Adalimumab 
n = 274 
(95% 

confidence 
interval) 

Adalimumab/
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 adalimumab/methotrexate 

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

combination therapy using the Mann-Whitney U test. 
c  p-value is from the pairwise comparison of adalimumab 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 
adalimumab/methotrexate combination therapy (63.8% and 61.2%, respectively) compared to 
methotrexate monotherapy (37.4% and 33.5% respectively, p < 0.001) and adalimumab 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 randomised to methotrexate 
monotherapy, adalimumab monotherapy and adalimumab/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 
adalimumab 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 
adalimumab 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 adalimumab/methotrexate combination therapy 
versus methotrexate monotherapy and adalimumab 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.  
 



65 

Paediatric plaque psoriasis  
 
The efficacy of adalimumab 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 adalimumab 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 
adalimumab 0.8 mg/kg had positive efficacy responses (e.g. PASI 75) than those randomised to 
0.4 mg/kg eow or MTX.  
 
Table 13. Paediatric plaque psoriasis efficacy results at 16 weeks 
 

 MTXa 
N = 37 

Adalimumab 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, adalimumab 0.8 mg/kg versus MTX 
c  P = 0.083, adalimumab 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.  
 
Adult plaque psoriasis  
 
The safety and efficacy of adalimumab 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 adalimumab 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 adalimumab 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 adalimumab 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 adalimumab 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 adalimumab 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 adalimumab followed by 40 mg every other week (starting one week after the initial dose) for 



66 

16 weeks. There are no data available comparing adalimumab 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 adalimumab 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 14 and 15).  
 
Table 14. Ps study I (REVEAL) efficacy results at 16 weeks 
 
 Placebo 

N = 398 
n (%) 

Adalimumab 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 PASI 75 response was calculated as centre-adjusted rate 
b  p < 0.001, adalimumab vs. placebo 
 
Table 15. Ps study II (CHAMPION) efficacy results at 16 weeks 
 
 Placebo  

N = 53  
n (%) 

MTX  
N = 110  
n (%) 

Adalimumab 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 adalimumab vs. placebo 
b  p < 0.001 adalimumab vs. methotrexate 
c  p < 0.01 adalimumab vs. placebo 
d  p < 0.05 adalimumab 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 adalimumab, 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 adalimumab therapy 
for 52 weeks in Psoriasis Study I, and continued adalimumab 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 



67 

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 adalimumab 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 adalimumab 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 adalimumab 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 adalimumab versus placebo in 217 adult patients 
with moderate to severe nail psoriasis. Patients received an initial dose of 80 mg adalimumab followed 
by 40 mg every other week (starting one week after the initial dose) or placebo for 26 weeks followed 
by open-label adalimumab 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 16). 
Adalimumab 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 16. 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 

Adalimumab 
40 mg eow 

N = 109 

Placebo 
N = 108 

Adalimumab 
40 mg eow 

N = 109 

Adalimumab 
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 -44.2a -11.5 -56.2a -72.2 

a  p<0.001, adalimumab vs. placebo 
 
Adalimumab treated patients showed statistically significant improvements at Week 26 compared with 
placebo in the DLQI.  
 
Adolescent hidradenitis suppurativa  
 
There are no clinical trials with adalimumab 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 



68 

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).  
 
Adult hidradenitis suppurativa  
 
The safety and efficacy of adalimumab 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 adalimumab 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 adalimumab in Period A were 
re-randomised in Period B to 1 of 3 treatment groups (adalimumab 40 mg every week, adalimumab 
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 adalimumab 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 adalimumab 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 adalimumab 
in Period A were re-randomised in Period B to 1 of 3 treatment groups (adalimumab 40 mg every 
week, adalimumab 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 adalimumab 40 mg 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 adalimumab 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 17). Patients treated with adalimumab 
had significantly reduced risk of disease flare during the initial 12 weeks of treatment.  
 
Table 17. Efficacy results at 12 weeks, HS studies I and II 
 
 HS study I HS study II 
 

Placebo 
Adalimumab 
40 mg weekly Placebo 

Adalimumab 
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%)*** 



69 

 HS study I HS study II 
 

Placebo 
Adalimumab 
40 mg weekly Placebo 

Adalimumab 
40 mg weekly 

≥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, adalimumab 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 adalimumab 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 adalimumab 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 adalimumab 40 mg weekly at Week 12, the HiSCR rate at 
Week 36 was higher in patients who continued weekly adalimumab than in patients in whom dosing 
frequency was reduced to every other week, or in whom treatment was withdrawn (see Table 18). 
 
Table 18. Proportion of patientsa achieving HiSCRb at Weeks 24 and 36 after treatment 
reassignment from weekly adalimumab at Week 12 
 

 
Placebo 

(treatment 
withdrawal) 

N = 73 

Adalimumab 40 mg 
every other week 

N = 70 

Adalimumab 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 adalimumab 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 
adalimumab therapy, the HiSCR rate at Week 48 was 68.3% and at Week 96 was 65.1%. Longer term 
treatment with adalimumab 40 mg weekly for 96 weeks identified no new safety findings.  
 
Among patients whose adalimumab treatment was withdrawn at Week 12 in Studies HS-I and HS-II, 
the HiSCR rate 12 weeks after re-introduction of adalimumab 40 mg weekly returned to levels similar 
to that observed before withdrawal (56.0%).  
 
Paediatric Crohn’s disease  
 
Adalimumab 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.  



70 

 
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 19.  
 
Table 19. 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 20. Rates of discontinuation of corticosteroids or 
immunomodulators are presented in Table 21.  
 
Table 20. 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 21. 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.  
 



71 

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.  
 
Adult Crohn’s disease  
 
The safety and efficacy of adalimumab were assessed in over 1,500 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 naïve patients were 
randomised to one of four treatment groups; placebo at Weeks 0 and 2, 160 mg adalimumab 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 adalimumab 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 22.  
 
Table 22. Induction of clinical remission and response (percent of patients) 
 
 CD Study I: Infliximab naïve patients CD Study II: Infliximab 

experienced patients 
 Placebo 

N = 74 
Adalimumab 

80/40 mg 
N = 75 

Adalimumab 
160/80 mg 

N = 76 

Placebo 
N = 166 

Adalimumab 
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 adalimumab 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 23. 



72 

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 23. Maintenance of clinical remission and response (percent of patients) 
 
 Placebo 40 mg Adalimumab every other week 

40 mg Adalimumab 
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 adalimumab versus placebo pairwise comparisons of proportions  
** p < 0.02 for adalimumab 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 adalimumab 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 adalimumab 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.  
 
Paediatric uveitis 
 
The safety and efficacy of adalimumab was assessed in a randomised, double-masked, controlled study 
of 90 paediatric patients from 2 to < 18 years of age with active JIA-associated non-infectious 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. 
 



73 

Clinical response 
 
Adalimumab significantly delayed the time to treatment failure, as compared to placebo (see Figure 1, 
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 1. Kaplan-Meier curves summarizing time to treatment failure in the paediatric uveitis 
study 

 
Note: P = Placebo (Number at Risk); H = Adalimumab (Number at Risk). 
 
Adult uveitis 
 
The safety and efficacy of adalimumab 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 
adalimumab 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. 
 



74 

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 t́ime 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 adalimumab. 
 
Clinical response 
 
Results from both studies demonstrated statistically significant reduction of the risk of treatment 
failure in patients treated with adalimumab versus patients receiving placebo (see Table 24). Both 
studies demonstrated an early and sustained effect of adalimumab on the treatment failure rate versus 
placebo (see Figure 2). 
 
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 Valueb 

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.  
 



75 

Figure 2. Kaplan-Meier curves summarizing time to treatment failure on or after Week 6 
(Study UV I) or Week 2 (Study UV II) 

 
 

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



76 

 
Quality of life 
 
Patient reported outcomes regarding vision-related functioning were measured in both clinical studies, 
using the NEI VFQ-25. Adalimumab 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 adalimumab for colour vision in Study UV I and for colour 
vision, peripheral vision and near vision in Study UV II. 
 
Immunogenicity 
 
Anti-adalimumab antibodies may develop during adalimumab treatment. 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.  
 
Paediatric population  
 
The European Medicines Agency has deferred the obligation to submit the results of the studies with 
the reference medicinal product containing adalimumab in one or more subsets of the paediatric 
population in ulcerative colitis (see section 4.2 for information on paediatric use).  
 
5.2 Pharmacokinetic properties  
 
Absorption and distribution  
 
Following the administration of 24 mg/m2 (up to a 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 (up to a 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 (up to a 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 



77 

(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 µg/ml for patients ≥ 40 kg 
(160/80 mg) and 10.6 ± 6.1 µg/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 µg/ml for the Standard Dose group and 3.5 ± 2.2 µg/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.  
 
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 µg/ml 
(without concomitant methotrexate) and 8 to 9 µg/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 adalimumab 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. 
 



78 

In patients with Crohn’s disease, the loading dose of 80 mg adalimumab on Week 0 followed by 
40 mg adalimumab on Week 2 achieves serum adalimumab trough concentrations of approximately 
5.5 μg/ml during the induction period. A loading dose of 160 mg adalimumab on Week 0 followed by 
80 mg adalimumab on Week 2 achieves serum adalimumab trough concentrations of approximately 
12 μg/ml during the induction period. Mean steady-state trough levels of approximately 7 μg/ml were 
observed in Crohn’s disease patients who received a maintenance dose of 40 mg adalimumab 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 μg/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  
 
Adalimumab 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 
cynomologous 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  
 
L-Histidine 
L-Histidine hydrochloride monohydrate 
Sucrose 
Edetate Disodium Dihydrate  
L-Methionine 
Polysorbate 80 
Water for injections 
 



79 

6.2 Incompatibilities  
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products.  
 
6.3 Shelf life  
 
3 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.  
 
A single Amsparity vial may be stored at temperatures up to a maximum of 30°C for a period of up 
to 30 days. The vial must be protected from light, and discarded if not used within the 30-day 
period. 
 
6.5 Nature and contents of container  
 
Amsparity 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:  
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  
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBER  
 
EU/1/19/1415/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION  
 
<Date of first authorisation: {DD month YYYY}> 
 
 
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.  
 

http://www.ema.europa.eu/
http://www.ema.europa.eu/


80 

This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1.  NAME OF THE MEDICINAL PRODUCT  
 
Amsparity 40 mg solution for injection in pre-filled syringe  
Amsparity 40 mg solution for injection in pre-filled pen  
 
 
2.  QUALITATIVE AND QUANTITATIVE COMPOSITION  
 
Amsparity 40 mg solution for injection in pre-filled syringe  
 
Each 0.8 ml single dose pre-filled syringe contains 40 mg of adalimumab.  
 
Amsparity 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 to very light brown solution.  
 
 
4.  CLINICAL PARTICULARS  
 
4.1  Therapeutic indications  
 
Rheumatoid arthritis  
 
Amsparity 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.  
 
Amsparity can be given as monotherapy in case of intolerance to methotrexate or when continued 
treatment with methotrexate is inappropriate.  
 
Adalimumab 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.  
 



81 

Juvenile idiopathic arthritis 
 
Polyarticular juvenile idiopathic arthritis  
 
Amsparity 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). Amsparity 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). Adalimumab has not been studied in 
patients aged less than 2 years.  
 
Enthesitis-related arthritis  
 
Amsparity 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)  
 
Amsparity 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  
 
Amsparity 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 
 
Amsparity 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. Adalimumab 
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 
 
Amsparity is indicated for the treatment of moderate to severe chronic plaque psoriasis in adult 
patients who are candidates for systemic therapy.  
 
Paediatric plaque psoriasis 
 
Amsparity 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 
 
Amsparity is indicated for the treatment of active moderate to severe hidradenitis suppurativa (HS) 
(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).  
 



82 

Crohn’s disease 
 
Amsparity 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 
 
Amsparity 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 
 
Amsparity 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.  
 
Uveitis 
 
Amsparity 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 
 
Amsparity 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  
 
Amsparity treatment should be initiated and supervised by specialist physicians experienced in the 
diagnosis and treatment of conditions for which Amsparity is indicated. Ophthalmologists are advised 
to consult with an appropriate specialist before initiation of treatment with Amsparity (see section 4.4). 
Patients treated with Amsparity should be given the patient reminder card.  
 
After proper training in injection technique, patients may self-inject with Amsparity if their physician 
determines that it is appropriate and with medical follow-up as necessary.  
 
During treatment with Amsparity, other concomitant therapies (e.g. corticosteroids and/or 
immunomodulatory agents) should be optimised.  
 
Posology 
 
Rheumatoid arthritis  
 
The recommended dose of Amsparity 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 Amsparity.  
 
Glucocorticoids, salicylates, non-steroidal anti-inflammatory drugs, or analgesics can be continued 
during treatment with Amsparity. Regarding combination with disease modifying anti-rheumatic drugs 
other than methotrexate see sections 4.4 and 5.1.  
 



83 

In monotherapy, some patients who experience a decrease in their response to Amsparity 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.  
 
Amsparity 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 adalimumab 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 Amsparity 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 Amsparity 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 Amsparity 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.  
 
Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs. 
 
Hidradenitis suppurativa  
 
The recommended Amsparity 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 Amsparity 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 Amsparity.  
 



84 

Continued therapy beyond 12 weeks should be carefully reconsidered in a patient with no 
improvement within this time period.  
 
Should treatment be interrupted, Amsparity 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).  
 
Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs. 
 
Crohn’s disease  
 
The recommended Amsparity 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), 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 Amsparity and signs and symptoms of disease recur, 
Amsparity 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 Amsparity 40 mg every other week may 
benefit from an increase in dosage to 40 mg Amsparity 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.  
 
Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs. 
 
Ulcerative colitis  
 
The recommended Amsparity 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 Amsparity 40 mg every other week may 
benefit from an increase in dosage to 40 mg Amsparity every week or 80 mg every other week.  
 
Available data suggest that clinical response is usually achieved within 2-8 weeks of treatment. 
Amsparity therapy should not be continued in patients failing to respond within this time period.  
 



85 

Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs. 
 
Uveitis  
 
The recommended dose of Amsparity 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 Amsparity alone. Treatment with Amsparity 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 Amsparity.  
 
It is recommended that the benefit and risk of continued long-term treatment should be evaluated on a 
yearly basis (see section 5.1).  
 
Amsparity 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 
 
Adalimumab 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 Amsparity for patients with polyarticular juvenile idiopathic arthritis from 
2 years of age is based on body weight (Table 1). Amsparity is administered every other week via 
subcutaneous injection.  
 
Table 1. Amsparity 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 adalimumab in patients aged less than 2 years for this indication.  
 
Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs. 
 



86 

Enthesitis-related arthritis  
 
The recommended dose of Amsparity for patients with enthesitis-related arthritis from 6 years of age is 
based on body weight (Table 2). Amsparity is administered every other week via subcutaneous 
injection.  
 
Table 2. Amsparity 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 
 
Adalimumab has not been studied in patients with enthesitis-related arthritis aged less than 6 years.  
 
Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs. 
 
Paediatric plaque psoriasis  
 
The recommended Amsparity dose for patients with plaque psoriasis from 4 to 17 years of age is based 
on body weight (Table 3). Amsparity is administered via subcutaneous injection.  
 
Table 3. Amsparity 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 Amsparity is indicated, the above guidance on dose and treatment duration should 
be followed.  
 
The safety of adalimumab in paediatric patients with plaque psoriasis has been assessed for a mean of 
13 months.  
 
There is no relevant use of adalimumab in children aged less than 4 years for this indication.  
 
Amsparity 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 adalimumab in adolescent patients with HS. The posology of 
adalimumab in these patients has been determined from pharmacokinetic modelling and simulation 
(see section 5.2).  
 
The recommended Amsparity 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 Amsparity 40 mg every other week, an increase in 
dosage to 40 mg every week or 80 mg every other week may be considered.  
 



87 

Antibiotics may be continued during treatment with Amsparity 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 Amsparity.  
 
Continued therapy beyond 12 weeks should be carefully reconsidered in a patient with no 
improvement within this time period.  
 
Should treatment be interrupted, Amsparity 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 adalimumab in children aged less than 12 years in this indication.  
 
Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs. 
 
Paediatric Crohn’s disease 
 
The recommended dose of Amsparity for patients with Crohn’s disease from 6 to 17 years of age is 
based on body weight (Table 4). Amsparity is administered via subcutaneous injection.  
 
Table 4. Amsparity 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 adalimumab in children aged less than 6 years for this indication.  
 
Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs. 
 
Paediatric uveitis 
 
The recommended dose of Amsparity for paediatric patients with uveitis from 2 years of age is based 
on body weight (Table 5). Amsparity is administered via subcutaneous injection.  
 
In paediatric uveitis, there is no experience in the treatment with adalimumab without concomitant 
treatment with methotrexate. 



88 

 
Table 5. Amsparity 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 Amsparity 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 an Amsparity loading dose in children < 6 years of age (see 
section 5.2). 
 
There is no relevant use of adalimumab 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). 
 
Amsparity may be available in other strengths and/or presentations depending on the individual 
treatment needs. 
 
Paediatric ulcerative colitis  
 
The safety and efficacy of adalimumab in children aged 4-17 years have not yet been established. No 
data are available. There is no relevant use of Amsparity in children aged less than 4 years for this 
indication.  
 
Psoriatic arthritis and axial spondyloarthritis including ankylosing spondylitis  
 
There is no relevant use of adalimumab in the paediatric population for the indications of ankylosing 
spondylitis and psoriatic arthritis.  
 
Method of administration  
 
Amsparity is administered by subcutaneous injection. Full instructions for use are provided in the 
package leaflet.  
 
Amsparity 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 the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded.  
 



89 

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 Amsparity. Because the 
elimination of adalimumab may take up to four months, monitoring should be continued throughout 
this period.  
 
Treatment with Amsparity 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 
Amsparity should be considered prior to initiating therapy (see Other opportunistic infections).  
 
Patients who develop a new infection while undergoing treatment with Amsparity should be monitored 
closely and undergo a complete diagnostic evaluation. Administration of Amsparity 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 Amsparity 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 adalimumab.  
 
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 adalimumab. Reports included cases of pulmonary and extra-pulmonary (i.e. disseminated) 
tuberculosis.  
 
Before initiation of therapy with Amsparity, 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, Amsparity 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 Amsparity, and in accordance with local 
recommendations.  



90 

 
Use of anti-tuberculosis prophylaxis treatment should also be considered before the initiation of 
Amsparity 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 adalimumab. Some patients who have been successfully treated for active 
tuberculosis have redeveloped tuberculosis while being treated with adalimumab.  
 
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 Amsparity.  
 
Other opportunistic infections  
 
Opportunistic infections, including invasive fungal infections have been observed in patients receiving 
adalimumab. 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 Amsparity 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 adalimumab, 
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 Amsparity. 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 Amsparity 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, Amsparity should be stopped and effective anti-viral therapy with 
appropriate supportive treatment should be initiated.  
 
Neurological events  
 
TNF-antagonists including adalimumab 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 Amsparity in patients with pre-existing or recent-onset central or peripheral nervous system 
demyelinating disorders; discontinuation of Amsparity 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 Amsparity therapy and regularly during treatment to assess for 
pre-existing or developing central demyelinating disorders.  
 



91 

Allergic reactions  
 
Serious allergic reactions associated with adalimumab were rare during clinical trials. Non-serious 
allergic reactions associated with adalimumab were uncommon during clinical trials. Reports of 
serious allergic reactions including anaphylaxis have been received following adalimumab 
administration. If an anaphylactic reaction or other serious allergic reaction occurs, administration of 
Amsparity should be discontinued immediately and appropriate therapy initiated.  
 
Immunosuppression  
 
In a study of 64 patients with rheumatoid arthritis that were treated with adalimumab, 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 adalimumab 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 
adalimumab should be carefully considered. A risk for the development of hepatosplenic T-cell 
lymphoma in patients treated with Amsparity 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 adalimumab is continued following development of malignancy. Thus, additional 
caution should be exercised in considering adalimumab 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 Amsparity. 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.  
 



92 

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 adalimumab. 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 Amsparity. Discontinuation of Amsparity 
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 adalimumab.  
 
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 adalimumab therapy.  
 
Patients on adalimumab 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 adalimumab. Amsparity should be used with 
caution in patients with mild heart failure (NYHA class I/II). Amsparity is contraindicated in moderate 
to severe heart failure (see section 4.3). Treatment with Amsparity must be discontinued in patients 
who develop new or worsening symptoms of congestive heart failure.  
 
Autoimmune processes  
 
Treatment with Amsparity may result in the formation of autoimmune antibodies. The impact of 
long-term treatment with adalimumab on the development of autoimmune diseases is unknown. If a 
patient develops symptoms suggestive of a lupus-like syndrome following treatment with Amsparity 
and is positive for antibodies against double-stranded DNA, further treatment with Amsparity 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 



93 

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 adalimumab. The 
long half-life of adalimumab should be taken into consideration if a surgical procedure is planned. A 
patient who requires surgery while on Amsparity should be closely monitored for infections, and 
appropriate actions should be taken. There is limited safety experience in patients undergoing 
arthroplasty while receiving adalimumab.  
 
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 adalimumab does not worsen or cause 
strictures.  
 
Elderly 
 
The frequency of serious infections among adalimumab-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.  
 
Excipient 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  
 
Adalimumab has been studied in rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and 
psoriatic arthritis patients taking adalimumab as monotherapy and those taking concomitant 
methotrexate. Antibody formation was lower when adalimumab was given together with methotrexate 
in comparison with use as monotherapy. Administration of adalimumab without methotrexate resulted 
in increased formation of antibodies, increased clearance and reduced efficacy of adalimumab (see 
section 5.1).  
 
The combination of Amsparity and anakinra is not recommended (see section 4.4 “Concurrent 
administration of biologic DMARDS or TNF-antagonists”).  
 
The combination of Amsparity 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 Amsparity treatment. 
 



94 

Pregnancy 
 
A large number (approximately 2,100) of prospectively collected pregnancies exposed to adalimumab 
resulting in live birth with known outcomes, including more than 1,500 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-randomised 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 TNFα, 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, Amsparity can be used during breast-feeding. 
 
Fertility 
 
Preclinical data on fertility effects of adalimumab are not available. 
 
4.7 Effects on ability to drive and use machines  
 
Adalimumab may have a minor influence on the ability to drive and use machines. Vertigo and visual 
impairment may occur following administration of Amsparity (see section 4.8).  
 
4.8 Undesirable effects  
 
Summary of the safety profile  
 
Adalimumab 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 



95 

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 adalimumab 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 adalimumab 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 adalimumab. TNF-antagonists, such as adalimumab 
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 adalimumab.  
 
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) 
 



96 

System organ class Frequency Adverse reaction 
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, 
Merkel cell carcinoma (neuroendocrine carcinoma of 
the skin)1 
 

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 
 



97 

System organ class Frequency Adverse reaction 
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 
 

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 
 



98 

System organ class Frequency Adverse reaction 
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 
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 
 



99 

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 

* 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 adalimumab weekly was consistent with the known 
safety profile of adalimumab.  
 



100 

Uveitis 
 
The safety profile for patients with uveitis treated with adalimumab every other week was consistent 
with the known safety profile of adalimumab.  
 
Description of selected adverse reactions 
 
Injection site reactions  
 
In the pivotal controlled trials in adults and children, 12.9% of patients treated with adalimumab 
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 adalimumab-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 adalimumab after the infection resolved.  
 
The incidence of serious infections was 0.04 per patient year in adalimumab-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 adalimumab, 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 adalimumab 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 adalimumab 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 an adalimumab 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 an 
adalimumab trial in paediatric patients with uveitis. 
 
During the controlled portions of pivotal adalimumab 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 adalimumab-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 
adalimumab 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 adalimumab-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 adalimumab-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 adalimumab-treated patients and 0.6 (0.1, 4.5) per 1,000 patient-years 
among control patients.  



101 

 
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 adalimumab 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 adalimumab 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 adalimumab 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 adalimumab-treated patients and 1.6% of control-treated patients.  
 
In controlled Phase 3 trials of adalimumab 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 adalimumab-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 adalimumab in patients with polyarticular juvenile idiopathic arthritis 
who were 2 to < 4 years.  
 
In controlled Phase 3 trials of adalimumab 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 
adalimumab-treated patients and 0.9% of controlled-treated patients.  
 
In the Phase 3 trial of adalimumab 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 adalimumab 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 
adalimumab-treated patients and 1.8% of control-treated patients.  
 
No ALT elevations ≥3 x ULN occurred in the Phase 3 trial of adalimumab in paediatric patients with 
plaque psoriasis.  
 
In controlled trials of adalimumab (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 



102 

period duration ranging from 12 to 16 weeks, ALT elevations ≥ 3 x ULN occurred in 0.3% of 
adalimumab-treated patients and 0.6% of control-treated patients.  
 
In controlled trials of adalimumab (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 adalimumab-treated and control-treated patients, respectively, ALT 
elevations ≥ 3 x ULN occurred in 2.4% of adalimumab-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 adalimumab and azathioprine/6-mercaptopurine compared 
with adalimumab 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  
 
Amsparity is a biosimilar medicinal product. Detailed information is available on the website of the 
European Medicines Agency http://www.ema.europa.eu. 
 
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 adalimumab, 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 

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metalloproteinases (MMP-1 and MMP-3) that produce tissue remodelling responsible for cartilage 
destruction were also decreased after adalimumab administration. Patients treated with adalimumab 
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 
adalimumab. 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  
 
Adalimumab was evaluated in over 3,000 patients in all rheumatoid arthritis clinical trials. The 
efficacy and safety of adalimumab 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 adalimumab 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 adalimumab 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 adalimumab 
every week for 52 weeks. The third group received 40 mg of adalimumab 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 adalimumab/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 
adalimumab 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 
adalimumab 40 mg every other week/methotrexate combination therapy, adalimumab 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 adalimumab 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 



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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 adalimumab-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.  
 
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 

Adalimumabb
/ MTXc 
n = 63 

Placebo 
n = 110 

Adalimumabb 
n = 113 

Placebo/ 
MTXc 

n = 200 

Adalimumabb
/ 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 adalimumab administered every other week 
c  MTX = methotrexate 
** p < 0.01, adalimumab 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 adalimumab 
40 mg every other week, 114 patients continued on adalimumab 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 adalimumab 
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 adalimumab 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, adalimumab-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 adalimumab and methotrexate led to faster and significantly greater ACR responses than 
methotrexate monotherapy and adalimumab monotherapy at Week 52 and responses were sustained at 
Week 104 (see Table 8).  
 



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Table 8. ACR responses in RA study V (percent of patients) 
 

Response MTX n = 257 
Adalimumab 

n = 274 
Adalimumab/MTX 

n = 268 p-value
a 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 adalimumab/methotrexate 
combination therapy using the Mann-Whitney U test.  

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

c  p-value is from the pairwise comparison of adalimumab 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 adalimumab 40 mg every other week, 
170 patients continued on adalimumab 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 adalimumab/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 adalimumab monotherapy. Adalimumab/methotrexate 
combination therapy was clinically and statistically superior to methotrexate (p < 0.001) and 
adalimumab 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 randomised to adalimumab monotherapy or 
adalimumab/methotrexate combination therapy who entered the open-label extension study, 
171 subjects completed 10 years of adalimumab treatment. Among those, 109 subjects (63.7%) were 
reported to be in remission at 10 years.  
 
Radiographic response  
 
In RA study III, where adalimumab-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. Adalimumab/methotrexate patients demonstrated significantly less radiographic 
progression than patients receiving methotrexate alone at 6 and 12 months (see Table 9).  
 
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 adalimumab 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 adalimumab 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.  
 



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Table 9. Radiographic mean changes over 12 months in RA study III 
 
 Placebo/ 

MTXa 
Adalimumab/MTX 
40 mg every other 

week 

Placebo/MTX- 
Adalimumab/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 
a  methotrexate 
b  95% confidence intervals for the differences in change scores between methotrexate and adalimumab. 
c  Based on rank analysis 
d  Joint 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) 

Adalimumab 
n = 274 
(95% 

confidence 
interval) 

Adalimumab/
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 adalimumab/methotrexate 

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

combination therapy using the Mann-Whitney U test 
c  p-value is from the pairwise comparison of adalimumab 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 
adalimumab/methotrexate combination therapy (63.8% and 61.2%, respectively) compared to 
methotrexate monotherapy (37.4% and 33.5%, respectively, p < 0.001) and adalimumab 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 randomised to methotrexate 
monotherapy, adalimumab monotherapy and adalimumab/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 
adalimumab 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 
adalimumab in all four studies support these findings, with statistically significant physical component 



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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 adalimumab/methotrexate combination therapy versus 
methotrexate monotherapy and adalimumab 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.  
 
Juvenile idiopathic arthritis (JIA)  
 
Polyarticular juvenile idiopathic arthritis (pJIA)  
 
The safety and efficacy of adalimumab 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 adalimumab 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 adalimumab 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 11.  
 
Table 11. 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 adalimumab 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.  
 



108 

Table 12. 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 Adalimumab / 

MTX 
(N = 38) 

Placebo / MTX 
(N = 37) 

Adalimumab 
(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 adalimumab 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 adalimumab and MTX compared to adalimumab alone. Taking these results into 
consideration, adalimumab 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 adalimumab 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 adalimumab 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, PedACR 30 response was 93.5% and 90.0%, respectively, using the 
observed data approach. The proportions of subjects with PedACR 50/70/90 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 
adalimumab throughout this time period. Overall, 20 subjects were treated for 60 weeks or longer.  
 
Enthesitis-related arthritis  
 
The safety and efficacy of adalimumab 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 adalimumab 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 adalimumab 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 
adalimumab group compared to -11.6% (median percent change -50.0%) in patients in the placebo 



109 

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 adalimumab 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.  
 
Axial spondyloarthritis  
 
Ankylosing spondylitis (AS)  
 
Adalimumab 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 adalimumab 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 adalimumab compared to 
placebo. Significant response was first observed at Week 2 and maintained through 24 weeks 
(Table 13).  
 
Table 13. Efficacy responses in placebo-controlled AS study – study I – reduction of signs and 
symptoms 
 
Response Placebo 

N = 107 
Adalimumab 

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 adalimumab and placebo at 
Weeks 2, 12 and 24  
a  Assessments in Ankylosing Spondylitis  
b  Bath Ankylosing Spondylitis Disease Activity Index 
 
Adalimumab 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).  
 



110 

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 adalimumab were assessed in two randomised, 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 adalimumab. 
 
Study nr-axSpA I 
 
In Study nr-axSpA I, adalimumab 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 adalimumab 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 adalimumab 40 mg every other week subcutaneously 
for up to an additional 144 weeks. Week 12 results showed statistically significant improvement of the 
signs and symptoms of active nr-axSpA in patients treated with adalimumab compared to placebo 
(Table 14).  
 
Table 14. Efficacy response in placebo-controlled study nr-axSpA I 
 
Double-blind 
Response at Week 12 

Placebo 
N = 94 

Adalimumab 
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 adalimumab  
f  high sensitivity C-Reactive Protein (mg/L)  
g  n = 73 placebo and n = 70 adalimumab  
h  Spondyloarthritis Research Consortium of Canada  
i  n = 84 placebo and adalimumab  
j  n = 82 placebo and n = 85 adalimumab  
***, **, * Statistically significant at p < 0.001, < 0.01, and < 0.05, respectively, for all comparisons between 
adalimumab and placebo.  
 
In the open-label extension, improvement in the signs and symptoms was maintained with adalimumab 
therapy through Week 156.  
 



111 

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 adalimumab-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. Adalimumab 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 adalimumab 40 mg eow 
for 28 weeks. 
 
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 randomised to receive either 
continued treatment with adalimumab 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 adalimumab 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 adalimumab 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 

 

 
TIME (WEEKS) 

Treatment Placebo  Adalimumab ∆ Censored 
Note: P = Placebo (Number at Risk (flared)); A = Adalimumab (Number at Risk (flared)). 

PR
O

B
A

B
IL

IT
Y

 O
F 

N
O

 F
L

A
R

E
 



112 

 
Among the 68 patients who flared in the group allocated to treatment withdrawal, 65 completed 
12 weeks of rescue therapy with adalimumab, 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 adalimumab 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 15). 
 
Table 15. Efficacy response in placebo-controlled period for study nr-axSpA II 
 
Double-blind  
Response at Week 68 

Placebo  
N = 153 

Adalimumab 
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 adalimumab 
and placebo. 
 
Psoriatic arthritis  
 
Adalimumab, 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 adalimumab 
was administered every other week.  
 
There is insufficient evidence of the efficacy of adalimumab in patients with ankylosing 
spondylitis-like psoriatic arthropathy due to the small number of patients studied.  
 
Table 16. ACR response in placebo-controlled psoriatic arthritis studies (percent of patients) 
 
 PsA study I PsA study II 
Response Placebo 

N = 162 
Adalimumab 

N = 151 
Placebo 
N = 49 

Adalimumab 
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 adalimumab and placebo  
* p < 0.05 for all comparisons between adalimumab and placebo  
N/A not applicable 
 



113 

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.  
 
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 
adalimumab or placebo and at Week 48 when all patients were on open-label adalimumab. A modified 
Total Sharp Score (mTSS), which included distal interphalangeal joints (i.e. not identical to the TSS 
used for rheumatoid arthritis), was used.  
 
Adalimumab 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 adalimumab group (at Week 48).  
 
In subjects treated with adalimumab with no radiographic progression from baseline to 
Week 48 (n = 102), 84% continued to show no radiographic progression through 144 weeks of 
treatment. Adalimumab 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 adalimumab 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 adalimumab 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 adalimumab 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 adalimumab 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 adalimumab 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 adalimumab 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 adalimumab followed by 40 mg every other week (starting one week after the initial dose) for 
16 weeks. There are no data available comparing adalimumab 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 adalimumab 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 17 and 18).  
 



114 

Table 17. Ps study I (REVEAL) efficacy results at 16 weeks 
 

 Placebo 
N = 398 
n (%) 

Adalimumab 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 PASI 75 response was calculated as centre-adjusted rate 
b  p < 0.001, adalimumab vs. placebo 
 
Table 18. Ps study II (CHAMPION) efficacy results at 16 weeks 
 
 Placebo  

N = 53  
n (%) 

MTX  
N = 110  
n (%) 

Adalimumab 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 adalimumab vs. placebo 
b  p < 0.001 adalimumab vs. methotrexate 
c  p < 0.01 adalimumab vs. placebo 
d  p < 0.05 adalimumab 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 adalimumab, 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 adalimumab therapy 
for 52 weeks in Psoriasis Study I, and continued adalimumab 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.  
 



115 

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 adalimumab 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 adalimumab 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 adalimumab 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 adalimumab versus placebo in 217 adult patients 
with moderate to severe nail psoriasis. Patients received an initial dose of 80 mg adalimumab followed 
by 40 mg every other week (starting one week after the initial dose) or placebo for 26 weeks followed 
by open-label adalimumab 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 19). 
Adalimumab 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 19. 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 

Adalimumab 
40 mg eow 

N = 109 

Placebo 
N = 108 

Adalimumab 
40 mg eow 

N = 109 

Adalimumab 
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 -44.2a -11.5 -56.2a -72.2 

a  p<0.001, adalimumab vs. placebo 
 
Adalimumab treated patients showed statistically significant improvements at Week 26 compared with 
placebo in the DLQI.  
 
Paediatric plaque psoriasis  
 
The efficacy of adalimumab 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 adalimumab 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 
adalimumab 0.8 mg/kg had positive efficacy responses (e.g. PASI 75) than those randomised to 
0.4 mg/kg eow or MTX.  
 



116 

Table 20. Paediatric plaque psoriasis efficacy results at 16 weeks 
 

 MTXa 
N = 37 

Adalimumab 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, adalimumab 0.8 mg/kg versus MTX 
c  P = 0.083, adalimumab 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.  
 
Hidradenitis suppurativa  
 
The safety and efficacy of adalimumab 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 adalimumab 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 adalimumab in Period A were 
re-randomised in Period B to 1 of 3 treatment groups (adalimumab 40 mg every week, adalimumab 
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 adalimumab 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 adalimumab 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 adalimumab 
in Period A were re-randomised in Period B to 1 of 3 treatment groups (adalimumab 40 mg every 
week, adalimumab 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 adalimumab 40 mg 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.  
 



117 

At Week 12, a significantly higher proportion of patients treated with adalimumab 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 21). Patients treated with adalimumab 
had significantly reduced risk of disease flare during the initial 12 weeks of treatment.  
 
Table 21. Efficacy results at 12 weeks, HS studies I and II 
 
 HS Study I HS Study II 

Placebo 
Adalimumab 40 mg 

Weekly Placebo 
Adalimumab 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, adalimumab 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 adalimumab 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 adalimumab 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 adalimumab 40 mg weekly at Week 12, the HiSCR rate at 
Week 36 was higher in patients who continued weekly adalimumab than in patients in whom dosing 
frequency was reduced to every other week, or in whom treatment was withdrawn (see Table 22).  
 
Table 22. Proportion of patientsa achieving HiSCRb at Weeks 24 and 36 after treatment 
reassignment from weekly adalimumab at Week 12 
 

 

Placebo 
(treatment 
withdrawal) 

N = 73 

Adalimumab 40 mg 
every other week 

N = 70 

Adalimumab 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 adalimumab 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 
adalimumab therapy, the HiSCR rate at Week 48 was 68.3% and at Week 96 was 65.1%. Longer term 
treatment with adalimumab 40 mg weekly for 96 weeks identified no new safety findings.  
 
Among patients whose adalimumab treatment was withdrawn at Week 12 in Studies HS-I and HS-II, 
the HiSCR rate 12 weeks after re-introduction of adalimumab 40 mg weekly returned to levels similar 
to that observed before withdrawal (56.0 %).  



118 

 
Adolescent hidradenitis suppurativa  
 
There are no clinical trials with adalimumab 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).  
 
Crohn’s disease  
 
The safety and efficacy of adalimumab 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 naïve patients were 
randomised to one of four treatment groups; placebo at Weeks 0 and 2, 160 mg adalimumab 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 adalimumab 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 23.  
 
Table 23. Induction of clinical remission and response (percent of patients) 
 
 CD study I: Infliximab naïve patients CD Study II: Infliximab 

experienced patients 
 Placebo 

N = 74 
Adalimumab 

80/40 mg 
N = 75 

Adalimumab 
160/80 mg 

N = 76 

Placebo 
N = 166 

Adalimumab 
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 adalimumab 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.  
 



119 

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 24. 
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 24. Maintenance of clinical remission and response (percent of patients) 
 
 Placebo 40 mg Adalimumab every other week 

40 mg Adalimumab 
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 adalimumab versus placebo pairwise comparisons of proportions  
** p < 0.02 for adalimumab 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 adalimumab 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 adalimumab 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.  
 
Paediatric Crohn’s disease  
 
Adalimumab 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.  
 



120 

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 25.  
 
Table 25. 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 26. Rates of discontinuation of corticosteroids or 
immunomodulators are presented in Table 27.  
 
Table 26. 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 27. 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).  



121 

 
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.  
 
Ulcerative colitis  
 
The safety and efficacy of multiple doses of adalimumab 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 adalimumab at Week 0 followed by 80 mg at Week 2, or 80 mg adalimumab 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 adalimumab 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 adalimumab 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 
adalimumab 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 28.  
 
Table 28. Response, remission and mucosal healing in study UC-II (percent of patients) 

 
 Placebo Adalimumab 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 daysa 6% 13%* 

   
Week 8 and 52 (N = 140) (N = 150) 

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 adalimumab vs. placebo pairwise comparison of proportions  
** p<0.001 for adalimumab 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.  



122 

 
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 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 adalimumab 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 
adalimumab 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 adalimumab. 
 
Clinical response  
 
Results from both studies demonstrated statistically significant reduction of the risk of treatment 
failure in patients treated with adalimumab versus patients receiving placebo (see Table 29). Both 
studies demonstrated an early and sustained effect of adalimumab on the treatment failure rate versus 
placebo (see Figure 2).  
 



123 

Table 29. 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 Valueb 

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) 

 
 
 



124 

 
Note: P# = Placebo (Number of Events/Number at Risk); A# = Adalimumab (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. Adalimumab 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 adalimumab for colour vision in Study UV I and for colour 
vision, peripheral vision and near vision in Study UV II. 
 
Paediatric uveitis 
 
The safety and efficacy of adalimumab was assessed in a randomised, double-masked, controlled study 
of 90 paediatric patients from 2 to < 18 years of age with active JIA-associated non-infectious 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 



125 

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 

 
Note: P = Placebo (Number at Risk); H = Adalimumab (Number at Risk). 

 
Immunogenicity 
 
Anti-adalimumab antibodies may develop during adalimumab treatment. 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.  
 



126 

Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of the studies with 
the reference medicinal product containing adalimumab in one or more subsets of the paediatric 
population in ulcerative colitis (see section 4.2 for information on paediatric use).  
 
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 µg/ml 
(without concomitant methotrexate) and 8 to 9 µg/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 (up to a 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 (up to a 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 
nonradiographic axial spondyloarthritis patients, the mean (±SD) trough steady-state concentration at 
Week 68 was 8.0 ± 4.6 µg/ml. 
 
In adult patients with psoriasis, the mean steady-state trough concentration was 5 µg/ml during 
adalimumab 40 mg every other week monotherapy treatment.  
 
Following the administration of 0.8 mg/kg (up to a 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 adalimumab 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.  
 



127 

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 adalimumab on Week 0 followed by 
40 mg adalimumab on Week 2 achieves serum adalimumab trough concentrations of approximately 
5.5 µg/ml during the induction period. A loading dose of 160 mg adalimumab on Week 0 followed by 
80 mg adalimumab on Week 2 achieves serum adalimumab trough concentrations of approximately 
12 µg/ml during the induction period. Mean steady-state trough levels of approximately 7 µg/ml were 
observed in Crohn’s disease patients who received a maintenance dose of 40 mg adalimumab 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 µg/ml for patients ≥ 40 kg 
(160/80 mg) and 10.6±6.1 µg/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 µg/ml for the Standard Dose group and 3.5±2.2 µg/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 adalimumab on Week 0 followed by 
80 mg adalimumab on Week 2 achieves serum adalimumab trough concentrations of approximately 
12 µg/ml during the induction period. Mean steady-state trough levels of approximately 8 µg/ml were 
observed in ulcerative colitis patients who received a maintenance dose of 40 mg adalimumab 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 µg/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). 
 
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). 



128 

 
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 
 
Adalimumab 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 
cynomologous 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  
 
L-Histidine 
L-Histidine hydrochloride monohydrate 
Sucrose 
Edetate Disodium Dihydrate  
L-Methionine 
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  
 
3 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.  



129 

 
A single Amsparity pre-filled syringe or pre-filled pen may be stored at temperatures up to a maximum 
of 30°C for a period of up to 30 days. The syringe or pen must be protected from light, and discarded 
if not used within the 30-day period.  
 
6.5 Nature and contents of container  
 
Amsparity 40 mg solution for injection in pre-filled syringe  
 
Amsparity 40 mg solution for injection in single-use pre-filled syringe (type I glass) with a plunger 
stopper (chlorobutyl rubber) and a needle with a needle shield (thermoplastic elastomer).  
 
Packs of:  
• 1 pre-filled syringe (0.8 ml sterile solution) with 2 alcohol pads, each pre-filled syringe is in a 

blister.  
• 2 pre-filled syringes (0.8 ml sterile solution) with 2 alcohol pads, each pre-filled syringe is in a 

blister.  
• 4 pre-filled syringes (0.8 ml sterile solution) with 4 alcohol pads, each pre-filled syringe is in a 

blister.  
• 6 pre-filled syringes (0.8 ml sterile solution) with 6 alcohol pads, each pre-filled syringe is in a 

blister.  
 
Amsparity 40 mg solution for injection in pre-filled pen  
 
Amsparity 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 
(chlorobutyl 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.  
• 2 pre-filled pens (0.8 ml sterile solution) with 2 alcohol pads.  
• 4 pre-filled pens (0.8 ml sterile solution) with 4 alcohol pads.  
• 6 pre-filled pens (0.8 ml sterile solution) with 6 alcohol pads.  
 
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  
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBERS  
 
Amsparity 40 mg solution for injection in pre-filled syringe 
 
EU/1/19/1415/003 
EU/1/19/1415/004 
EU/1/19/1415/005 



130 

EU/1/19/1415/006 
 
Amsparity 40 mg solution for injection in pre-filled pen  
 
EU/1/19/1415/007 
EU/1/19/1415/008 
EU/1/19/1415/009 
EU/1/19/1415/010 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION  
 
<Date of first authorisation: {DD month YYYY}> 

 
 
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.  
 
 

http://www.ema.europa.eu/
http://www.ema.europa.eu/


131 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND MANUFACTURER 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 

 
 
 



132 

 
A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 

MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer of the biological active substance 
 
Wyeth BioPharma  
Division of Wyeth Pharmaceuticals LLC 
One Burtt Road 
Andover, MA 01810 
USA 
 
Name and address of the manufacturer responsible for batch release  
 
Pfizer Service Company BVBA 
Hoge Wei 10 
Zaventem 1930 
Belgium 
 
 
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 authorisation 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.  

 



133 

• Additional risk minimisation measures  
 

The Patient Reminder Cards (adult and paediatric) contain the following key elements 
 
-  infections, including tuberculosis 
-  cancer 
-  nervous system problems 
-  vaccinations 



134 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



135 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



136 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Amsparity 20 mg solution for injection in pre-filled syringe  
adalimumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE  
 
One 0.4 ml pre-filled syringe contains 20 mg adalimumab. 
 
 
3. LIST OF EXCIPIENTS  
 
Excipients: L-histidine, L-histidine hydrochloride monohydrate, sucrose, edetate disodium dihydrate, 
L-methionine, 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 
 
 



137 

9. SPECIAL STORAGE CONDITIONS  
 
Store in a refrigerator. Do not freeze. 
 
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  
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER  
 
EU/1/19/1415/001 
 
 
13. BATCH NUMBER  
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE  
 
Amsparity 20 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE  
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
PC  
SN  
NN  
 



138 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY BACKING TEXT 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Amsparity 20 mg solution for injection in pre-filled syringe  
adalimumab  
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Pfizer Europe MA EEIG 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. OTHER 
 
For storage information, see package leaflet. 
 
For single use only. 
 
For paediatric use 
 
 



139 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  
 
SYRINGE LABEL  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION  
 
Amsparity 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/0.4 ml 
 
 
6. OTHER  
 
 



140 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Amsparity 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: L-histidine, L-histidine hydrochloride monohydrate, sucrose, edetate disodium dihydrate, 
L-methionine, polysorbate 80, 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  
 
 



141 

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  
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER  
 
EU/1/19/1415/002 
 
 
13. BATCH NUMBER  
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE  
 
Amsparity 40 mg/0.8 ml  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE  
 
2D barcode carrying the unique identifier included.  
 
 



142 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
PC  
SN  
NN  
 
 



143 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
INNER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Amsparity 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: L-histidine, L-histidine hydrochloride monohydrate, sucrose, edetate disodium dihydrate, 
L-methionine, polysorbate 80, 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  
 
 



144 

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  
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER  
 
EU/1/19/1415/002 
 
 
13. BATCH NUMBER  
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE  
 
Amsparity 40 mg/0.8 ml  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE  
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
 



145 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  
 
VIAL LABEL  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION  
 
Amsparity 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  
 
 



146 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Amsparity 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: L-histidine, L-histidine hydrochloride monohydrate, sucrose, edetate disodium dihydrate, 
L-methionine, polysorbate 80, and water for injections. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Solution for injection 
1 pre-filled syringe  
2 alcohol pads  
 
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.  
 
 



147 

7. OTHER SPECIAL WARNING, IF NECESSARY  
 
 
8. EXPIRY DATE  
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS  
 
Store in a refrigerator. Do not freeze.  
 
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  
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER  
 
EU/1/19/1415/003 
EU/1/19/1415/004 
EU/1/19/1415/005 
EU/1/19/1415/006 
 
 
13. BATCH NUMBER  
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE  
 
Amsparity 40 mg  
 
 



148 

17. UNIQUE IDENTIFIER – 2D BARCODE  
 
2D barcode carrying the unique identifier included.  
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
PC  
SN  
NN  
 
 



149 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY BACKING TEXT 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Amsparity 40 mg solution for injection in pre-filled syringe  
adalimumab  
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Pfizer Europe MA EEIG 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. OTHER 
 
For storage information, see package leaflet.  
 
For single use only  
 
 



150 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  
 
SYRINGE LABEL  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION  
 
Amsparity 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  
 
 



151 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Amsparity 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: L-histidine, L-histidine hydrochloride monohydrate, sucrose, edetate disodium dihydrate, 
L-methionine, 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.  
 
 



152 

7. OTHER SPECIAL WARNING, IF NECESSARY  
 
 
8. EXPIRY DATE  
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS  
 
Store in a refrigerator. Do not freeze.  
 
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  
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER  
 
EU/1/19/1415/007 
EU/1/19/1415/008 
EU/1/19/1415/009 
EU/1/19/1415/010 
 
 
13. BATCH NUMBER  
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE  
 
Amsparity 40 mg  
 
 



153 

17. UNIQUE IDENTIFIER – 2D BARCODE  
 
2D barcode carrying the unique identifier included.  
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
PC  
SN  
NN  
 
 



154 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  
 
PEN LABEL  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION  
 
Amsparity 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  
 
 



155 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



156 

Package leaflet: Information for the patient 
 

Amsparity 20 mg solution for injection in pre-filled syringe 
adalimumab 

 

 
 

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects your child may get. See the end of 
section 4 for how to report side effects. 
 
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 child’s 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 Amsparity and during 
treatment with Amsparity. Keep this patient reminder card with you or your child. 

− If you have any further questions, ask your child’s 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 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 Amsparity is and what it is used for 
2. What you need to know before your child uses Amsparity 
3. How to use Amsparity 
4. Possible side effects 
5. How to store Amsparity 
6. Contents of the pack and other information 
 
 
1. What Amsparity is and what it is used for 
 
Amsparity contains the active substance adalimumab, a medicine that acts on your child’s body’s 
immune (defence) system. 
 
Amsparity is intended for the treatment of the following inflammatory diseases: 
• polyarticular juvenile idiopathic arthritis 
• paediatric enthesitis-related arthritis 
• paediatric plaque psoriasis 
• paediatric Crohn’s disease 
• paediatric uveitis 
 
The active ingredient in Amsparity, adalimumab, is a monoclonal antibody. Monoclonal antibodies are 
proteins that attach to a specific target in the body. 
 
The target of adalimumab is another 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 



157 

above. By attaching to TNFα, Amsparity blocks its action and reduces the 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. 
 
Amsparity is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged 2 
to 17 years. 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 Amsparity to treat his/her 
polyarticular juvenile idiopathic arthritis. 
 
Paediatric enthesitis-related arthritis 
 
Paediatric enthesitis-related arthritis is an inflammatory disease of the joints and the places where 
tendons join the bone. 
 
Amsparity is used to treat enthesitis-related arthritis in children and adolescents aged 6 to 17 years. 
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 Amsparity to treat his/her 
enthesitis-related arthritis. 
 
Paediatric plaque psoriasis 
 
Plaque psoriasis is an inflammatory 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. 
 
Amsparity is used to treat severe chronic plaque psoriasis in children and adolescents aged 4 to 
17 years for whom medicines applied to the skin and treatment with UV light have either not worked 
very well or are not suitable. 
 
Paediatric Crohn’s disease 
 
Crohn’s disease is an inflammatory disease of the gut. 
 
Amsparity is used to treat Crohn’s disease in children and adolescents aged 6 to 17 years. 
 
If your child has Crohn’s disease, your child will first be given other medicines. If your child does not 
respond well enough to these medicines, your child will be given Amsparity to reduce the signs and 
symptoms of his/her Crohn’s disease. 
 
Paediatric uveitis 
 
Non-infectious uveitis is an inflammatory disease affecting certain parts 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). Amsparity works by reducing this inflammation. 
 
Amsparity is used to treat children and adolescents with chronic non-infectious uveitis from 2 years of 
age with inflammation affecting the front of the eye. 
 
Your child may first be given other medicines. If these medicines do not work well enough, your child 
will be given Amsparity to reduce the signs and symptoms of his/her disease. 
 



158 

 
2. What you need to know before your child uses Amsparity  
 
Do not use Amsparity 
 
• 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, sepsis (blood poisoning) or 

opportunistic infections (unusual infections associated with a weakened immune system). It is 
important that you tell your child’s doctor if your child has symptoms of infections, for example, 
fever, wounds, feeling tired, dental problems (see “Warnings and precautions”). 

 
• if your child has moderate or severe heart failure. It is important to tell your child’s 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 Amsparity.  
 
It is important that you and your child’s doctor record the brand name and batch number of your 
child’s medication. 
 
Allergic reactions 
 
• If your child has allergic reactions with symptoms such as chest tightness, wheezing, dizziness, 

swelling or rash, do not inject more Amsparity and contact your child’s 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 child’s doctor before starting Amsparity. If you are 
unsure, contact your child’s doctor. 

 
• Your child might get infections more easily while he/she is receiving Amsparity 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, or other 
opportunistic infections (unusual infectious organisms), and sepsis (blood poisoning). In rare 
cases, these infections may be life-threatening. It is important to tell your child’s doctor if your 
child gets symptoms such as fever, wounds, feeling tired or dental problems. Your child’s doctor 
may recommend temporarily stopping Amsparity. 

 
Tuberculosis (TB) 
 
• As cases of tuberculosis have been reported in patients treated with adalimumab, your child’s 

doctor will check your child for signs and symptoms of tuberculosis before starting Amsparity. 
This will include a thorough medical evaluation including your child’s medical history and 
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 child’s doctor if your child has ever had tuberculosis, or if 
he/she has been in close contact with someone who has had tuberculosis. If your child has active 
tuberculosis, do not use Amsparity. 

 



159 

• Tuberculosis can develop during therapy even if your child had 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 child’s doctor 
immediately. 

 
Travel / recurrent infection 
 
• Tell your child’s doctor if your child has lived or travelled in regions where fungal infections 

such as histoplasmosis, coccidioidomycosis or blastomycosis are endemic (found). 
 
• Tell your child’s doctor if your child has had infections which keep coming back or other 

conditions that increase the risk of infections. 
 
• You and your child’s doctor should pay special attention to signs of infection while your child is 

being treated with Amsparity. It is important to tell your child’s doctor if your child gets 
symptoms of infections, such as fever, wounds, feeling tired or dental problems. 

 
Hepatitis B 
 
• Tell your child’s doctor if your child is a carrier of the hepatitis B virus (HBV), if he/she has 

active HBV infection or if you think he/she might be at risk of getting HBV. Your child’s doctor 
should test your child for HBV. Adalimumab can reactivate HBV infection in people who carry 
the virus. In some rare cases, especially if your child is taking other medicines that suppress the 
immune system, reactivation of HBV infection can be life-threatening.  

 
Surgery or dental procedure 
 
• If your child is about to have surgery or dental procedures, tell your child’s doctor that he/she is 

taking Amsparity. Your child’s doctor may recommend temporarily stopping Amsparity. 
 
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 child’s doctor will decide if he/she should 
receive or continue to receive Amsparity. Tell your child’s doctor immediately if your child gets 
symptoms like changes in vision, weakness in arms or legs or numbness or tingling in any part 
of the body. 

 
Vaccination 
 
• Certain vaccines contain living but weakened forms of disease-causing bacteria or viruses that 

may cause infections and should not be given during treatment with Amsparity. Check with your 
child’s doctor before your child receives any vaccines. It is recommended that, if possible, 
children be given all the scheduled vaccinations for their age before they start treatment with 
Amsparity. If your child received Amsparity while she was pregnant, her baby may be at higher 
risk for getting an infection for up to about five months after the last Amsparity dose she 
received during pregnancy. It is important that you tell her baby's doctors and other health care 
professionals about your child’s Amsparity use during her pregnancy so they can decide when 
her baby should receive any vaccine. 

 
Heart failure 
 
• It is important to tell your child’s doctor if your child has had or has a serious heart condition. If 

your child has mild heart failure and is being treated with Amsparity, his/her heart failure status 



160 

must be closely monitored by your child’s doctor. 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 child’s doctor immediately.  

 
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. If your child develops a fever that does not go away, bruises 
or bleeds very easily or looks very pale, call your child’s doctor right away. Your child’s doctor 
may decide to stop treatment. 

 
Cancer 
 
• There have been very rare cases of certain kinds of cancer in children and adults taking 

adalimumab or other TNFα blockers. People with more serious rheumatoid arthritis who have 
had the disease for a long time may have a higher than average risk of getting lymphoma and 
leukaemia (cancers that affects blood cells and bone marrow). If your child takes Amsparity 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 adalimumab. Some of 
those patients were also treated with the medicines azathioprine or mercaptopurine. Tell your 
child’s doctor if your child is taking azathioprine or mercaptopurine with Amsparity. 

 
• In addition, cases of non-melanoma skin cancer have been observed in patients taking 

adalimumab. If new areas of damaged skin appear during or after treatment or if existing marks 
or areas of damage change appearance, tell your child’s 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 TNFα 
blocker. If your child has COPD, or is a heavy smoker, you should discuss with your child’s 
doctor whether treatment with a TNFα blocker is appropriate for your child. 

 
Autoimmune disease 
 
• On rare occasions, treatment with Amsparity could result in lupus-like syndrome. Contact your 

child’s doctor if symptoms such as persistent unexplained rash, fever, joint pain or tiredness 
occur. 

 
Other medicines and Amsparity 
 
Tell your child’s doctor or pharmacist if your child is taking, has recently taken or might take any 
other medicines. 
 
Amsparity can be taken together with methotrexate or certain disease-modifying anti-rheumatic agents 
(for example, sulfasalazine, hydroxychloroquine, leflunomide and injectable gold preparations), 
corticosteroids or pain medications including non-steroidal anti-inflammatory drugs (NSAIDs). 
 
Your child should not take Amsparity with medicines containing the active substances anakinra or 
abatacept due to increased risk of serious infection. The combination of adalimumab as well as other 
TNF-antagonists and anakinra or abatacept is not recommended based upon the possible increased risk 
for infections, including serious infections and other potential pharmacological interactions. If you 
have questions, please ask your child’s 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 Amsparity treatment. 
 



161 

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. 
 
Amsparity 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 adalimumab during pregnancy compared with mothers with the same disease who did not 
receive adalimumab. 
 
Amsparity can be used during breast-feeding. 
 
If your child receives Amsparity 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 
Amsparity 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 
 
Amsparity may have a small effect on your child’s ability to drive, cycle or use machines. Room 
spinning sensation (vertigo) and vision disturbances may occur after taking Amsparity. 
 
Amsparity contains sodium 
 
This medicine contains less than 1 mmol of sodium (23 mg) per 0.8 ml dose, that is to say essentially 
‘sodium-free’. 
 
 
3. How to use Amsparity 
 
Always use this medicine exactly as your child’s doctor, nurse or pharmacist has told you. Check with 
your doctor, nurse or pharmacist if you are not sure. 
 
The recommended doses for Amsparity in each of the approved uses are shown in the following table. 
Your child’s doctor may prescribe another strength of Amsparity if your child needs a different dose. 
 
Amsparity is injected under the skin (subcutaneous use). 
 
Polyarticular juvenile idiopathic arthritis 
Age or body weight How much and how often to 

take? 
Notes 

Children and adolescents 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 

 
Paediatric enthesitis-related arthritis 
Age or body weight How much and how often to 

take? 
Notes 

Children and adolescents from 
6 years of age weighing 30 kg 
or more 

40 mg every other week Not applicable 



162 

Paediatric enthesitis-related arthritis 
Age or body weight How much and how often to 

take? 
Notes 

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. 

 



163 

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 child’s 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. 
Amsparity 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 child’s 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. 
Amsparity is recommended for 
use in combination with 
methotrexate. 

 
Method and route of administration 
 
Amsparity is administered by injection under the skin (by subcutaneous injection). 
 
Detailed instructions on how to inject Amsparity, the Instructions for Use, are provided at the 
end of this leaflet. 
 
If you use more Amsparity than you should 
 
If you accidentally inject your child with Amsparity more frequently than you should, call your child’s 
doctor or pharmacist and explain that your child has taken more than required. Always take the outer 
carton of the medicine with you, even if it is empty. 
 
If you forget to use Amsparity 
 
If you forget to give your child an Amsparity injection, you should inject the next dose of Amsparity 
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 your child stops using Amsparity 
 
The decision to stop using Amsparity should be discussed with your child’s doctor. Your child’s 
symptoms may return upon stopping treatment. 
 
If you have any further questions on the use of this medicine, ask your child’s 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 Amsparity injection. 
 



164 

Seek medical attention urgently, if you notice any of the following signs: 
 
• 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 child’s doctor as soon as possible, if you notice any of the following: 
 
• signs and symptoms of infection such as fever, feeling sick, wounds, dental problems, burning 

on urination, feeling weak or tired or coughing; 
• symptoms of nerve problems such as tingling, numbness, double vision, or arm or leg weakness; 
• signs of skin cancer such as a bump or open sore that does not heal; 
• signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, 

paleness. 
 
The signs and symptoms described above can represent the side effects listed below, which have been 
observed with adalimumab: 
 
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 (belly) pain; 
• nausea and vomiting; 
• rash; 
• pain in the muscles or joints. 
 
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; 
• mouth 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; 
• symptoms of 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 room spinning); 
• sensation of heart beating rapidly; 



165 

• high blood pressure; 
• flushing; 
• haematoma (a solid swelling with clotted blood); 
• 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 (a build-up of fluid in the body which causes the affected tissue to swell); 
• fever; 
• reduction in blood platelets which increases risk of bleeding or bruising; 
• impaired healing. 
 
Uncommon (may affect up to 1 in 100 people) 
 
• opportunistic (unusual) 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, including cancer that affects the lymph system (lymphoma) and melanoma (a type of 

skin cancer); 
• immune disorders that could affect the lungs, skin and lymph nodes (most commonly as a 

condition called sarcoidosis); 
• vasculitis (inflammation of blood vessels); 
• tremor (shaking); 
• neuropathy (nerve damage); 
• stroke; 
• double vision; 
• 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; 



166 

• facial oedema (swelling of the face); 
• gallbladder inflammation, gallbladder stones; 
• fatty liver (build up of fat in liver cells); 
• night sweats; 
• scar; 
• abnormal muscle breakdown; 
• systemic lupus erythematosus (an immune disorder 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 inflammation of the optic nerve to the eye, and Guillain-Barré 

syndrome, a condition 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 wall of the gut); 
• hepatitis (liver inflammation); 
• reactivation of hepatitis B infection; 
• 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 (life-threatening reaction with flu-like symptoms and blistering 

rash); 
• facial oedema (swelling of the face) associated with allergic reactions; 
• erythema multiforme (inflammatory skin rash); 
• lupus-like syndrome; 
• angioedema (localised 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); 
• liver failure; 
• worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle 

weakness). 
 
Some side effects observed with adalimumab 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; 
• raised liver enzymes. 
 



167 

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) 
 
• raised 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 Amsparity 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is 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 travelling), a single Amsparity pre-filled syringe may be stored at 
room temperature (up to 30°C) for a maximum period of 30 days – be sure to protect it from light. 
Once removed from the refrigerator for room temperature storage, the syringe must be used within 30 
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 child’s doctor or 
pharmacist how to throw away medicines you no longer use. These measures will help protect the 
environment. 
 
 



168 

6. Contents of the pack and other information  
 
What Amsparity contains 
 
The active substance is adalimumab. 
 
The other ingredients are L-histidine, L-histidine hydrochloride monohydrate, sucrose, edetate 
disodium dihydrate, L-methionine, polysorbate 80, and water for injections. 
 
What the Amsparity pre-filled syringe looks like and contents of the pack  
 
Amsparity 20 mg solution for injection in pre-filled syringe for paediatric use is supplied as a sterile 
solution of 20 mg adalimumab dissolved in 0.4 ml solution. 
 
The Amsparity pre-filled syringe is a glass syringe containing a clear, colourless to very light brown 
solution of adalimumab. 
 
The Amsparity pre-filled syringe is available in a pack containing 2 pre-filled syringes with 2 alcohol 
pads.  
 
Amsparity may be available as a vial, a pre-filled syringe and/or a pre-filled pen. 
 
Marketing Authorisation Holder 
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
Manufacturer 
 
Pfizer Service Company BVBA 
Hoge Wei 10 
Zaventem 1930 
Belgium 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Luxembourg/Luxemburg 
Pfizer NV/SA 
Tél/Tel: +32 (0)2 554 62 11  

Kύπρος 
PFIZER EΛΛAΣ A.E. (CYPRUS BRANCH) 
Τηλ: +357 22 817690 
 

Česká Republika 
Pfizer, spol.  s r.o. 
Tel: +420-283-004-111 
 

Magyarország 
Pfizer Kft. 
Tel: +36 1 488 3700 
 

Danmark 
Pfizer ApS 
Tlf: +45 44 201 100 
 

Malta 
Drugsales Ltd  
Tel: +356 21 419070/1/2 
 

Deutchland: 
Pfizer Pharma PFE GmbH 
Tel: +49 (0)800 8535555 
 

Nederland 
Pfizer bv 
Tel: +31 (0)10 406 43 01 
 



169 

България 
Пфайзер Люксембург САРЛ, 
Клон България 
Teл: +359 2 970 4333 
 

Norge 
Pfizer AS 
Tlf: +47 67 52 61 00 
 

Eesti 
Pfizer Luxembourg SARL Eesti filiaal 
Tel: +372 666 7500 
 

Österreich 
Pfizer Corporation Austria Ges.m.b.H. 
Tel: +43 (0)1 521 15-0 
 

Ελλάδα 
PFIZER EΛΛAΣ A.E. 
Τηλ.: +30 210 67 85 800 
 

Polska 
Pfizer Polska Sp. z o.o. 
Tel.: +48 22 335 61 00 
 

España 
Pfizer S.L. 
Tel: +34 91 490 99 00 
 
 

Portugal 
Laboratórios Pfizer, Lda. 
Tel: +351 21 423 5500 

France 
Pfizer  
Tél: +33 (0)1 58 07 34 40 
 

România 
Pfizer România S.R.L 
Tel: +40 (0) 21 207 28 00 
 

Hrvatska 
Pfizer Croatia d.o.o. 
Tel: +385 1 3908 777 
 

Slovenija 
Pfizer Luxembourg SARL, Pfizer, podružnica 
za svetovanje s področja farmacevtske 
dejavnosti, Ljubljana 
Tel: +386 (0)1 52 11 400 
 

Ireland 
Pfizer Healthcare Ireland 
Tel: +1800 633 363 (toll free) 
Tel: +44 (0)1304 616161 
 

Slovenská Republika 
Pfizer Luxembourg SARL, organizačná zložka 
Tel: +421 2 3355 5500 
 

Ísland 
Icepharma hf. 
Tel: +354 540 8000 
 

Suomi/Finland 
Pfizer PFE Finland Oy 
Puh/Tel: +358 (0)9 430 040 
 
 

Italia 
Pfizer Italia S.r.l.  
Tel: +39 06 33 18 21 
 

Sverige 
Pfizer AB 
Tel: +46 (0)8 550 520 00 
 

Latvija 
Pfizer Luxembourg SARL filiāle Latvijā 
Tel. +371 67035775 
 

United Kingdom 
Pfizer Limited 
Tel: +44 (0)1304 616161 
 

Lietuva 
Pfizer Luxembourg SARL filialas Lietuvoje 
Tel. +3705 2514000 

 

 
 
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. 
 

http://www.ema.europa.eu/
http://www.ema.europa.eu/


170 

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. 



171 

INSTRUCTIONS FOR USE  
Amsparity (adalimumab) 

20 mg 
Single-dose Pre-filled Syringe, for subcutaneous injection 

 
Keep this leaflet. These instructions show step-by-step how to prepare and give an injection.  
Store Amsparity pre-filled syringe in the refrigerator between 2°C to 8°C.  
Store Amsparity pre-filled syringe in the original carton until use to protect from direct sunlight. 
If needed, for example when you and your child are traveling, you may store Amsparity 
pre-filled syringe at room temperature up to 30°C for up to 30 days. 
Keep Amsparity, injection supplies, and all other medicines out of the reach of children. 
 
 
Amsparity for injection comes in a disposable single use pre-filled syringe that contains a single dose 
of medicine. 
Do not try to inject Amsparity to your child until you have read and understood the Instructions for 
Use. If your child’s doctor, nurse or pharmacist decides that you may be able to give injections of 
Amsparity to your child at home, you should receive training on the correct way to prepare and inject 
Amsparity. 
It is also important to talk to your child’s doctor, nurse or pharmacist to be sure you understand your 
child’s Amsparity dosing instructions. To help you remember when to inject Amsparity, you can mark 
your calendar ahead of time. Talk to your child’s doctor, nurse or pharmacist if you have any questions 
about the correct way to inject Amsparity. 
After proper training, the Amsparity injection can be given by your child or given by another person, 
for example, a family member or friend. 
 
1. Supplies you need  

 
• You will need the following supplies for each injection of Amsparity. Find a clean, flat surface 

to place the supplies on. 
o 1 Amsparity pre-filled syringe in a tray, inside the carton 
o 1 alcohol swab, inside the carton 
o 1 cotton ball or gauze pad (not included in the Amsparity carton) 
o A suitable sharps container (not included in the Amsparity carton). 
Important: If you have any questions about your child’s Amsparity pre-filled syringe or 
medicine, talk to your child’s doctor, nurse or pharmacist. 

 
 

 
 
 



172 

2. Getting ready 
 
• Remove Amsparity carton from the refrigerator. 
• Open the carton and take out the tray containing the pre-filled syringe. 
• Check the carton and tray; do not use if: 

o the expiration date has passed 
o it has been frozen or thawed 
o it has been dropped, even if it looks undamaged 
o it has been out of the refrigerator for more than 30 days 
o it appears to be damaged 
o the seals on a new carton are broken. 

• If any of the above apply, dispose of the pre-filled syringe in the same way as a used syringe. 
You will need a new pre-filled syringe to give your child’s injection. 

• Wash your hands with soap and water, and dry completely.  
If you have any questions about your child’s medicine, please talk to your child’s doctor, nurse 
or pharmacist. 

 
 

 
 
 
• Peel back the paper seal on the tray. 
• Remove 1 pre-filled syringe from the tray and put the original carton with any unused pre-filled 

syringes back in the refrigerator. 
• Do not use the syringe if it appears to be damaged. 
• The pre-filled syringe may be used straight from the refrigerator. 
• You may find that using the pre-filled syringe at room temperature reduces stinging or 

discomfort. Leave the pre-filled syringe at room temperature away from direct sunlight for 15 to 
30 minutes before your child’s injection. 

• Do not remove the needle cover from the pre-filled syringe until you are ready to inject. 
Always hold the pre-filled syringe by the barrel to prevent damage. 

 
 



173 

 
 
 
• Look carefully at your child’s medicine in the window.  
• Gently tilt the pre-filled syringe back and forth to check the medicine. 
• Do not shake the pre-filled syringe. Shaking can damage your child’s medicine. 
• Make sure the medicine in the pre-filled syringe is clear and colourless to very light brown and 

free from flakes or particles. It is normal to see one or more air bubbles in the window. Do not 
attempt to remove air bubbles. 
If you have any questions about your child’s medicine, please talk to your child’s doctor, nurse 
or pharmacist.  

 
 

 
 
 
• Choose a different site each time you give your child an injection. 
• Do not inject into bony areas or areas on your child’s skin that are bruised, red, sore (tender) or 

hard. Avoid injecting into areas with scars or stretch marks. 
o If your child has psoriasis, do not inject directly into any raised, thick, red, or scaly skin 

patches or lesions on your child’s skin. 
• Do not inject through your child’s clothes. 
• Wipe the injection site with the alcohol swab. 
• Allow the injection site to dry. 
 
 



174 

 
 
 
• Hold the pre-filled syringe by the syringe barrel. Carefully pull the needle cover straight off and 

away from your body when you are ready to inject. 
• It is normal to see a few drops of medicine at the needle tip when you remove the needle cover. 
• Throw the needle cover away into a sharps disposal container. 

Note: Be careful when you handle the pre-filled syringe to avoid an accidental needle stick 
injury. 

 

 
 
 
• Gently pinch up a fold of skin in the cleaned injection site area. 
• Insert the needle to its full depth into the skin, at a 45 degree angle, as shown.  
• After the needle is inserted, release the pinched skin. 

Important: Do not re-insert the needle into your child’s skin. If the needle has already been 
inserted into the skin and you change your mind about where to inject, you will need a 
replacement pre-filled syringe. 

 



175 

 
 
 

• Using slow and constant pressure, push the plunger rod all the way down until the barrel is 
empty. It usually takes 2 to 5 seconds to deliver the dose. 
Note: It is recommended to hold the pre-filled syringe in the skin for an additional 5 seconds 
after the plunger has been pressed down completely. 

• Pull the needle out of the skin at the same angle at which it entered. 
 
 

 
 

• Check that your child’s medicine has completely emptied from the pre-filled syringe. 
• Never re-insert the needle. 
• Never re-cap the needle. 

Note: If the grey stopper is not in the position shown, you may not have injected all of your 
child’s medicine. Talk to your child’s doctor, nurse or pharmacist right away. 

 
 



176 

 
 
 
• Dispose of the syringe straight away as instructed by your child’s doctor, nurse or pharmacist 

and in accordance with local health and safety laws. 
 
 

 
 
 
• Look closely at your child’s injection site. If there is blood, use a clean cotton ball or gauze pad 

to press lightly on the injection area for a few seconds.  
• Do not rub the site. 

Note: Store any unused syringes in the refrigerator in the original carton. 
 
 
See over for 
Package leaflet: Information for the patient 



177 

Package leaflet: Information for the patient 
 

Amsparity 40 mg/0.8 ml solution for injection 
adalimumab 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects your child may get. See the end of 
section 4 for how to report side effects. 
 
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 child’s 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 Amsparity and during 
treatment with Amsparity. Keep this patient reminder card with you or your child.  

− If you have any further questions, ask your child’s 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 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 Amsparity is and what it is used for  
2. What you need to know before your child uses Amsparity  
3. How to use Amsparity  
4. Possible side effects  
5. How to store Amsparity  
6. Contents of the pack and other information 
 
 
1. What Amsparity is and what it is used for  
 
Amsparity contains the active substance adalimumab, a medicine that acts on your child’s body’s 
immune (defence) system.  
 
Amsparity is intended for the treatment of the following inflammatory diseases: 
• polyarticular juvenile idiopathic arthritis  
• paediatric enthesitis-related arthritis 
• paediatric plaque psoriasis  
• adolescent hidradenitis suppurativa  
• paediatric Crohn’s disease 
• paediatric uveitis  
 
The active ingredient in Amsparity, adalimumab, is a monoclonal antibody. Monoclonal antibodies are 
proteins that attach to a specific target in the body.  
 
The target of adalimumab is another 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, Amsparity blocks its action and reduces the 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.  
 



178 

Amsparity is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged 2 
to 17 years. 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 Amsparity to treat his/her 
polyarticular juvenile idiopathic arthritis. 
 
Paediatric enthesitis-related arthritis 
 
Paediatric enthesitis-related arthritis is an inflammatory disease of the joints and the places where 
tendons join the bone. 
 
Amsparity is used to treat enthesitis-related arthritis in children and adolescents aged 6 to 17 years. 
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 Amsparity to treat his/her 
enthesitis-related arthritis. 
 
Paediatric plaque psoriasis 
 
Plaque psoriasis is an inflammatory 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.  
 
Amsparity is used to treat severe plaque psoriasis in children and adolescents aged 4 to 17 years for 
whom medicines applied to the skin and treatment with UV light have either not worked very well or 
are not suitable.  
 
Adolescent hidradenitis suppurativa  
 
Hidradenitis suppurativa (sometimes called acne inversa) is a long-term 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.  
 
Amsparity is used to treat hidradenitis suppurativa in adolescents from 12 years of age. Amsparity can 
reduce the number of nodules and abscesses your child has, and the pain that is often associated with 
the disease. Your child may first be given other medicines. If these medicines do not work well 
enough, your child will be given Amsparity.  
 
Paediatric Crohn’s disease  
 
Crohn’s disease is an inflammatory disease of the gut.  
 
Amsparity is used to treat Crohn’s disease in children and adolescents aged 6 to 17 years.  
 
If your child has Crohn’s disease, your child will first be given other medicines. If your child does not 
respond well enough to these medicines, your child will be given Amsparity to reduce the signs and 
symptoms of his/her Crohn’s disease.  
 
Paediatric uveitis  
 
Non-infectious uveitis is an inflammatory disease affecting certain parts 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). Amsparity works by reducing this inflammation. 
 
Amsparity is used to treat children and adolescents with chronic non-infectious uveitis from 2 years of 
age with inflammation affecting the front of the eye.  



179 

 
Your child may first be given other medicines. If these medicines do not work well enough, your 
child will be given Amsparity to reduce the signs and symptoms of his/her disease. 
 
 
2. What you need to know before your child uses Amsparity  
 
Do not use Amsparity  
 
• 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, sepsis (blood poisoning) or 

opportunistic infections (unusual infections associated with a weakened immune system). It is 
important that you tell your child’s doctor if your child has symptoms of infections, for example, 
fever, wounds, feeling tired, dental problems (see “Warnings and precautions”).  

 
• if your child has moderate or severe heart failure. It is important to tell your child’s 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 Amsparity. 
 
It is important that you and your child’s doctor record the brand name and batch number of your 
child’s medication. 
  
Allergic reactions 
 
• If your child has allergic reactions with symptoms such as chest tightness, wheezing, dizziness, 

swelling or rash, do not inject more Amsparity and contact your child’s 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 child’s doctor before starting Amsparity. If you are 
unsure, contact your child’s doctor.  

 
• Your child might get infections more easily while he/she is receiving Amsparity 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, or other 
opportunistic infections (unusual infectious organisms), and sepsis (blood poisoning). In rare 
cases, these infections may be life-threatening. It is important to tell your child’s doctor if your 
child gets symptoms such as fever, wounds, feeling tired or dental problems. Your child’s doctor 
may recommend temporarily stopping Amsparity.  

 
Tuberculosis (TB) 
 
• As cases of tuberculosis have been reported in patients treated with adalimumab, your child’s 

doctor will check your child for signs and symptoms of tuberculosis before starting Amsparity. 
This will include a thorough medical evaluation including your child’s medical history and 
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. 

  



180 

• It is very important that you tell your child’s doctor if your child has ever had tuberculosis, or if 
he/she has been in close contact with someone who has had tuberculosis. If your child has active 
tuberculosis, do not use Amsparity. 

 
• Tuberculosis can develop during therapy even if your child had 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 child’s doctor 
immediately.  

 
Travel / recurrent infection 
 
• Tell your child’s doctor if your child has lived or travelled in regions where fungal infections 

such as histoplasmosis, coccidioidomycosis or blastomycosis are endemic (found).  
 
• Tell your child’s doctor if your child has had infections which keep coming back or other 

conditions that increase the risk of infections.  
 
• You and your child’s doctor should pay special attention to signs of infection while your child is 

being treated with Amsparity. It is important to tell your child’s doctor if your child gets 
symptoms of infections, such as fever, wounds, feeling tired or dental problems.  

 
Hepatitis B 
 
• Tell your child’s doctor if your child is a carrier of the hepatitis B virus (HBV), if he/she has 

active HBV infection or if you think he/she might be at risk of getting HBV. Your child’s doctor 
should test your child for HBV. Adalimumab can reactivate HBV infection in people who carry 
the virus. In some rare cases, especially if your child is taking other medicines that suppress the 
immune system, reactivation of HBV infection can be life-threatening.  

 
Surgery or dental procedure 
 
• If your child is about to have surgery or dental procedures, tell your child’s doctor that he/she is 

taking Amsparity. Your child’s doctor may recommend temporarily stopping Amsparity.  
 
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 child’s doctor will decide if he/she should 
receive or continue to receive Amsparity. Tell your child’s doctor immediately if your child gets 
symptoms like changes in vision, weakness in arms or legs or numbness or tingling in any part 
of the body.  

 
Vaccination 
 
• Certain vaccines contain living but weakened forms of disease-causing bacteria or viruses that 

may cause infections and should not be given during treatment with Amsparity. Check with your 
child’s doctor before your child receives any vaccines. It is recommended that, if possible, 
children be given all the scheduled vaccinations for their age before they start treatment with 
Amsparity. If your child received Amsparity while she was pregnant, her baby may be at higher 
risk for getting an infection for up to about five months after the last Amsparity dose she 
received during pregnancy. It is important that you tell her baby’s doctors and other health care 
professionals about your child’s Amsparity use during her pregnancy so they can decide when 
her baby should receive any vaccine.  

 



181 

Heart failure 
 
• It is important to tell your child’s doctor if your child has had or has a serious heart condition. If 

your child has mild heart failure and is being treated with Amsparity, his/her heart failure status 
must be closely monitored by your child’s doctor. 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 child’s doctor immediately.  

 
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. If your child develops a fever that does not go away, bruises 
or bleeds very easily or looks very pale, call your child’s doctor right away. Your child’s doctor 
may decide to stop treatment.  

 
Cancer 
 
• There have been very rare cases of certain kinds of cancer in children and adults taking 

adalimumab or other TNFα blockers. People with more serious rheumatoid arthritis who have 
had the disease for a long time may have a higher than average risk of getting lymphoma and 
leukaemia (cancers that affects blood cells and bone marrow). If your child takes Amsparity 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 adalimumab. Some of 
those patients were also treated with the medicines azathioprine or mercaptopurine. Tell your 
child’s doctor if your child is taking azathioprine or mercaptopurine with Amsparity.  

 
• In addition, cases of non-melanoma skin cancer have been observed in patients taking 

adalimumab. If new areas of damaged skin appear during or after treatment or if existing marks 
or areas of damage change appearance, tell your child’s 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 TNFα 
blocker. If your child has COPD, or is a heavy smoker, you should discuss with your child’s 
doctor whether treatment with a TNFα blocker is appropriate for your child.  

 
Autoimmune disease 
 
• On rare occasions, treatment with Amsparity could result in lupus-like syndrome. Contact your 

child’s doctor if symptoms such as persistent unexplained rash, fever, joint pain or tiredness 
occur. 

 
Other medicines and Amsparity  
 
Tell your child’s doctor or pharmacist if your child is taking, has recently taken or might take any 
other medicines.  
 
Amsparity can be taken together with methotrexate or certain disease-modifying anti-rheumatic agents 
(for example, sulfasalazine, hydroxychloroquine, leflunomide and injectable gold preparations), 
corticosteroids or pain medications including non-steroidal anti-inflammatory drugs (NSAIDs).  
 
Your child should not take Amsparity with medicines containing the active substances anakinra or 
abatacept due to increased risk of serious infection. The combination of adalimumab as well as other 
TNF-antagonists and anakinra or abatacept is not recommended based upon the possible increased risk 
for infections, including serious infections and other potential pharmacological interactions. If you 
have questions, please ask your child’s doctor.  
 



182 

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 Amsparity 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. 
 
Amsparity 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 adalimumab during pregnancy compared with mothers with the same disease who did not 
receive adalimumab. 
 
Amsparity can be used during breast-feeding. 
 
If your child receives Amsparity 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 
Amsparity 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  
 
Amsparity may have a small effect on your child’s ability to drive, cycle or use machines. Room 
spinning sensation (vertigo) and vision disturbances may occur after taking Amsparity.  
 
Amsparity contains sodium 
 
This medicine contains less than 1 mmol of sodium (23 mg) per 0.8 ml dose, that is to say essentially 
‘sodium-free’. 
 
 
3. How to use Amsparity  
 
Always use this medicine exactly as your child’s doctor, nurse or pharmacist has told you. Check with 
your child’s doctor, nurse or pharmacist if you are not sure. Your child’s doctor may prescribe another 
strength of Amsparity if your child needs a different dose. 
 
Amsparity is injected under the skin (subcutaneous use). 
 
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 Amsparity is 20 mg every other week.  
 
Children and adolescents from 2 years of age weighing 30 kg or more 
 
The recommended dose of Amsparity 40 mg every other week.  
 
Children and adolescents with enthesitis-related arthritis  
 
Children and adolescents from 6 years of age weighing 15 kg to less than 30 kg 
 
The recommended dose of Amsparity is 20 mg every other week. 
 



183 

Children and adolescents from 6 years of age weighing 30 kg or more 
 
The recommended dose of Amsparity 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 Amsparity 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 Amsparity 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 Amsparity 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 this dose does not work well enough, 
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 starting two weeks later.  
 
Thereafter, the usual dose is 20 mg every other week. If this dose does not work well enough, 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 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. If this dose does not work well enough, your 
child’s doctor may increase the dosage to 40 mg every week or 80 mg every other week.  
 
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 Amsparity 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 Amsparity is 40 mg every other week with methotrexate. 



184 

 
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  
 
Amsparity is administered by injection under the skin (by subcutaneous injection).  
 
Detailed instructions on how to inject Amsparity are provided in the ‘Instructions for use’. 
 
If you use more Amsparity than you should  
 
If you accidentally inject your child with a larger amount of Amsparity liquid, or if you inject 
Amsparity more frequently than you should, call your child’s doctor or pharmacist and explain that 
your child has taken more than required. Always take the outer carton or the vial of the medicine with 
you, even if it is empty.  
 
If you use less Amsparity than you should  
 
If you accidentally inject your child with a smaller amount of Amsparity liquid, or if you inject your 
child with Amsparity less frequently than you should, call your child’s doctor or pharmacist and 
explain that your child has taken less than required. Always take the outer carton or the vial of the 
medicine with you, even if it is empty.  
 
If you forget to use Amsparity  
 
If you forget to give your child an Amsparity injection, you should inject the next dose of Amsparity 
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 your child stops using Amsparity  
 
The decision to stop using Amsparity should be discussed with your child’s doctor. Your child’s 
symptoms may return upon stopping treatment.  
 
If you have any further questions on the use of this medicine, ask your child’s 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 Amsparity injection.  
 
Seek medical attention urgently, if you notice any of the following signs: 
 
• 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 child’s doctor as soon as possible, if you notice any of the following:  
 
• signs and symptoms of infection such as fever, feeling sick, wounds, dental problems, burning on 

urination, feeling weak or tired or coughing;  
• symptoms of nerve problems such as tingling, numbness, double vision, or arm or leg weakness;  
• signs of skin cancer such as a bump or open sore that does not heal;  



185 

• signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, 
paleness.  

 
The signs and symptoms described above can represent the side effects listed below, which have been 
observed with adalimumab: 
 
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 (belly) pain;  
• nausea and vomiting;  
• rash;  
• pain in the muscles or joints.  
 
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;  
• mouth 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;  
• symptoms of 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 room spinning);  
• sensation of heart beating rapidly;  
• high blood pressure;  
• flushing;  
• haematoma (a solid swelling with clotted blood);  
• 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;  



186 

• 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 (a build-up of fluid in the body which causes the affected tissue to swell);  
• fever;  
• reduction in blood platelets which increases risk of bleeding or bruising;  
• impaired healing.  
 
Uncommon (may affect up to 1 in 100 people) 
 
• opportunistic (unusual) 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, including cancer that affects the lymph system (lymphoma) and melanoma (a type of 

skin cancer);  
• immune disorders that could affect the lungs, skin and lymph nodes (most commonly as a 

condition called sarcoidosis);  
• vasculitis (inflammation of blood vessels);  
• tremor (shaking);  
• neuropathy (nerve damage);  
• stroke;  
• double vision; 
• 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 (build up of fat in liver cells);  
• night sweats;  
• scar;  
• abnormal muscle breakdown;  
• systemic lupus erythematosus (an immune disorder including inflammation of skin, heart, lung, 

joints and other organ systems);  
• sleep interruptions;  
• impotence;  
• inflammations.  
 



187 

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 inflammation of the optic nerve to the eye, and Guillain-Barré 

syndrome, a condition 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 wall of the gut);  
• hepatitis (liver inflammation);  
• reactivation of hepatitis B infection;  
• 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 (life-threatening reaction with flu-like symptoms and blistering 

rash);  
• facial oedema (swelling of the face) associated with allergic reactions;  
• erythema multiforme (inflammatory skin rash);  
• lupus-like syndrome; 
• angioedema (localised 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);  
• liver failure;  
• worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle 

weakness).  
 
Some side effects observed with adalimumab 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;  
• raised 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.  
 



188 

Uncommon (may affect up to 1 in 100 people) 
 
• raised 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 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 Amsparity  
 
Keep this medicine out of the sight and reach of children.  
 
Do not use this medicine after the expiry date which is stated on the label / 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.  
 
Alternative Storage: 
 
When needed (for example, when travelling), a single Amsparity vial may be stored at room 
temperature (up to 30°C) for a maximum period of 30 days – be sure to protect it from light. Once 
removed from the refrigerator for room temperature storage, the vial must be used within 30 days 
or discarded, even if it is returned to the refrigerator. 
 
You should record the date when the vial 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 child’s 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 Amsparity contains 
 
The active substance is adalimumab.  
 
The other ingredients are L-histidine, L-histidine hydrochloride monohydrate, sucrose, edetate 
disodium dihydrate, L-methionine, polysorbate 80, and water for injections.  
 
What the Amsparity vial looks like and contents of the pack  
 
Amsparity 40 mg solution for injection in vials is supplied as a sterile solution of 40 mg adalimumab 
dissolved in 0.8 ml solution.  
 
The Amsparity vial is a glass vial containing a clear, colourless to very light brown 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.  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


189 

 
Amsparity may be available as a vial, a pre-filled syringe and/or a pre-filled pen.  
 
Marketing Authorisation Holder  
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
Manufacturer  
 
Pfizer Service Company BVBA 
Hoge Wei 10 
Zaventem 1930 
Belgium 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder.  
 
België/Belgique/Belgien 
Luxembourg/Luxemburg 
Pfizer NV/SA 
Tél/Tel: +32 (0)2 554 62 11  

Kύπρος 
PFIZER EΛΛAΣ A.E. (CYPRUS BRANCH) 
Τηλ: +357 22 817690 
 

Česká Republika 
Pfizer, spol.  s r.o. 
Tel: +420-283-004-111 
 

Magyarország 
Pfizer Kft. 
Tel: +36 1 488 3700 
 

Danmark 
Pfizer ApS 
Tlf: +45 44 201 100 
 

Malta 
Drugsales Ltd  
Tel: +356 21 419070/1/2 
 

Deutchland: 
Pfizer Pharma PFE GmbH 
Tel: +49 (0)800 8535555 
 

Nederland 
Pfizer bv 
Tel: +31 (0)10 406 43 01 
 

България 
Пфайзер Люксембург САРЛ, 
Клон България 
Teл: +359 2 970 4333 
 

Norge 
Pfizer AS 
Tlf: +47 67 52 61 00 
 

Eesti 
Pfizer Luxembourg SARL Eesti filiaal 
Tel: +372 666 7500 
 

Österreich 
Pfizer Corporation Austria Ges.m.b.H. 
Tel: +43 (0)1 521 15-0 
 

Ελλάδα 
PFIZER EΛΛAΣ A.E. 
Τηλ.: +30 210 67 85 800 
 

Polska 
Pfizer Polska Sp. z o.o. 
Tel.: +48 22 335 61 00 
 

España 
Pfizer S.L. 
Tel: +34 91 490 99 00 
 
 

Portugal 
Laboratórios Pfizer, Lda. 
Tel: +351 21 423 5500 



190 

France 
Pfizer  
Tél: +33 (0)1 58 07 34 40 
 

România 
Pfizer România S.R.L 
Tel: +40 (0) 21 207 28 00 
 

Hrvatska 
Pfizer Croatia d.o.o. 
Tel: +385 1 3908 777 
 

Slovenija 
Pfizer Luxembourg SARL, Pfizer, podružnica 
za svetovanje s področja farmacevtske 
dejavnosti, Ljubljana 
Tel: +386 (0)1 52 11 400 
 

Ireland 
Pfizer Healthcare Ireland 
Tel: +1800 633 363 (toll free) 
Tel: +44 (0)1304 616161 
 

Slovenská Republika 
Pfizer Luxembourg SARL, organizačná zložka 
Tel: +421 2 3355 5500 
 

Ísland 
Icepharma hf. 
Tel: +354 540 8000 
 

Suomi/Finland 
Pfizer PFE Finland Oy 
Puh/Tel: +358 (0)9 430 040 
 
 

Italia 
Pfizer Italia S.r.l.  
Tel: +39 06 33 18 21 
 

Sverige 
Pfizer AB 
Tel: +46 (0)8 550 520 00 
 

Latvija 
Pfizer Luxembourg SARL filiāle Latvijā 
Tel. +371 67035775 
 

United Kingdom 
Pfizer Limited 
Tel: +44 (0)1304 616161 
 

Lietuva 
Pfizer Luxembourg SARL filialas Lietuvoje 
Tel. +3705 2514000 

 

 
 
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. 

http://www.ema.europa.eu/
http://www.ema.europa.eu/


191 

INSTRUCTIONS FOR USE 
 
Instructions for preparing and giving an injection of Amsparity: 
 
The following instructions explain how to inject Amsparity. Please read the instructions carefully and 
follow them step by step.  
Do not try to inject Amsparity to your child until you have read and understood the Instructions for 
Use. If your child’s doctor, nurse or pharmacist decides that you may be able to give injections of 
Amsparity to your child at home, you should receive training on the correct way to prepare and inject 
Amsparity. 
 
It is also important to talk to your child’s doctor, nurse or pharmacist to be sure you understand your 
child’s Amsparity dosing instructions. To help you remember when to inject Amsparity, you can mark 
your calendar ahead of time. Talk to your child’s doctor, nurse or pharmacist if you have any questions 
about the correct way to inject Amsparity. 
 
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 do not know the 

amount, STOP HERE and talk to your child’s doctor, nurse or pharmacist for further 
instruction. 
 

• You will need a special container for waste, such as a sharps container or as instructed by your 
child’s doctor, nurse 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 Amsparity for injection (3) 
o Two alcohol pads (4) 
o One needle (5) 

 



192 

 
 
Amsparity is a liquid that is clear and colourless to very light brown and free from flakes or particles. 
DO NOT use if the liquid has flakes or particles in it. 
 
2) Preparing the Amsparity 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. 

 

 
 

• Pop off the 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. 



193 

 

 
• 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. 

 
• 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 the 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 
child’s Amsparity provider for a replacement. DO NOT try to reinsert the white plunger rod. 
 



194 

 
 
• 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. 

 
 

• While holding the vial, push the white plunger rod all the way down. This step is important to 
get the proper dose. 

 

 
 
 

Dose + 0.1 ml 
 



195 

• 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, for example 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. 

 
 

 
 



196 

 
• 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 
Amsparity 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 talk to 
your child’s doctor, nurse or pharmacist. 
 

• 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. 

 
 

• Pull the needle package off, but DO NOT remove the clear needle cap. 



197 

 
• 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 the 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 talk to your child’s doctor. 
 

o If your child has psoriasis, do not inject directly into any raised, thick, red, or scaly 
skin patches or lesions on the skin. 

 
• 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. 

 
 

 
 



198 

 
• 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 Amsparity 
 
• 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. 
• Using slow and constant pressure, 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. 
• Check that your child’s medicine has completely emptied from the pre-filled syringe. 

 
 

 
 

 



199 

• 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 

child’s doctor, nurse 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. 
 



200 

 
Package leaflet: Information for the patient 

 
Amsparity 40 mg solution for injection in pre-filled syringe 

adalimumab 
 

 
 

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
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 Amsparity and during treatment 
with Amsparity. 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 Amsparity is and what it is used for  
2. What you need to know before you use Amsparity  
3. How to use Amsparity  
4. Possible side effects  
5. How to store Amsparity  
6. Contents of the pack and other information 
 
 
1. What Amsparity is and what it is used for  
 
Amsparity contains the active substance adalimumab, a medicine that acts on your body’s immune 
(defence) system. 
 
Amsparity is intended for the treatment of the following inflammatory diseases: 
• rheumatoid arthritis,  
• polyarticular juvenile idiopathic arthritis,  
• paediatric enthesitis-related arthritis,  
• ankylosing spondylitis,  
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis,  
• psoriatic arthritis,  
• psoriasis,  
• hidradenitis suppurativa,  
• Crohn’s disease,  
• ulcerative colitis and  



201 

• non-infectious uveitis.  
 
The active ingredient in Amsparity, adalimumab, is a monoclonal antibody. Monoclonal antibodies are 
proteins that attach to a specific target in the body.  
 
The target of adalimumab is another 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, Amsparity blocks its action and reduces the inflammation in these 
diseases.  
 
Rheumatoid arthritis  
 
Rheumatoid arthritis is an inflammatory disease of the joints.  
 
Amsparity 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 these medicines do not work well enough, you will be given Amsparity to treat your rheumatoid 
arthritis.  
 
Amsparity can also be used to treat severe, active and progressive rheumatoid arthritis without 
previous methotrexate treatment.  
 
Amsparity can slow down the damage to the cartilage and bone of the joints caused by the disease and 
improve physical function.  
 
Usually, Amsparity is used with methotrexate. If your doctor considers that methotrexate is 
inappropriate, Amsparity can be given alone.  
 
Polyarticular juvenile idiopathic arthritis 
 
Polyarticular juvenile idiopathic arthritis is an inflammatory disease of the joints that usually first 
appears in childhood.  
 
Amsparity is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged 
2 to 17 years. Patients may first be given other disease-modifying medicines, such as methotrexate. If 
these medicines do not work well enough, patients will be given Amsparity to treat their polyarticular 
juvenile idiopathic arthritis.  
 
Paediatric enthesitis-related arthritis 
 
Paediatric enthesitis-related arthritis is an inflammatory disease of the joints and the places where 
tendons join the bone. 
 
Amsparity is used to treat enthesitis-related arthritis in children and adolescents aged 6 to 17 years. 
Patients may first be given other disease-modifying medicines, such as methotrexate. If these 
medicines do not work well enough, patients will be given Amsparity to treat their 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.  
 
Amsparity is used in adults to treat these conditions. If you have ankylosing spondylitis or axial 
spondyloarthritis without radiographic evidence of ankylosing spondylitis, you will first be given other 



202 

medicines. If these medicines do not work well enough, you will be given Amsparity to reduce the 
signs and symptoms of your disease.  
 
Psoriatic arthritis  
 
Psoriatic arthritis is an inflammation of the joints associated with psoriasis.  
 
Amsparity is used to treat psoriatic arthritis in adults. Amsparity can 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 an inflammatory 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.  
 
Amsparity is used to treat moderate to severe plaque psoriasis in adults. Amsparity is also used to treat 
severe plaque psoriasis in children and adolescents aged 4 to 17 years for whom medicines applied to 
the skin and treatment with UV light have either not worked very well or are not suitable.  
 
Hidradenitis suppurativa in adults and adolescents  
 
Hidradenitis suppurativa (sometimes called acne inversa) is a long-term 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.  
 
Amsparity is used to treat hidradenitis suppurativa in adults and adolescents from 12 years of age. 
Amsparity 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 these medicines do not work 
well enough, you will be given Amsparity.  
 
Crohn’s disease in adults and children  
 
Crohn’s disease is an inflammatory disease of the gut.  
 
Amsparity 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 Amsparity to reduce the signs and symptoms of your Crohn’s 
disease.  
 
Ulcerative colitis  
 
Ulcerative colitis is an inflammatory disease of the bowel.  
 
Amsparity is used to treat ulcerative colitis in adults. If you have ulcerative colitis you will first be 
given other medicines. If these medicines do not work well enough, you will be given Amsparity 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. 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). Amsparity works by reducing this inflammation. 



203 

 
Amsparity 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.  
 
You may first be given other medicines. If these medicines do not work well enough, you will be 
given Amsparity to reduce the signs and symptoms of your disease. 
 
 
2. What you need to know before you use Amsparity  
 
Do not use Amsparity 
 
• if you are allergic to adalimumab or any of the other ingredients of this medicine (listed in 

section 6).  
 

• if you have a severe infection, including active tuberculosis, sepsis (blood poisoning) or 
opportunistic infections (unusual infections associated with a weakened immune system). It is 
important that you tell your doctor if you have symptoms of infections, for example, fever, 
wounds, feeling tired, dental problems (see “Warnings and precautions”).  
 

• 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 Amsparity. 
 
It is important that you and your doctor record the brand name and batch number of your medication. 
 
Allergic reactions 
 
• If you have allergic reactions with symptoms such as chest tightness, wheezing, dizziness, 

swelling or rash, do not inject more Amsparity 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 Amsparity. If you are unsure, 
contact your doctor.  

 
• You might get infections more easily while you are receiving Amsparity 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, or other opportunistic 
infections (unusual infectious organisms) and sepsis (blood poisoning). In rare cases, these 
infections may 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 temporarily 
stopping Amsparity.  

 
Tuberculosis (TB) 
 
• As cases of tuberculosis have been reported in patients treated with adalimumab, your doctor 

will check you for signs and symptoms of tuberculosis before starting Amsparity. This will 
include a thorough medical evaluation including your medical history and screening tests (for 



204 

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 had preventative treatment for 

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.  

 
Travel / recurrent infection 
 
• Tell your doctor if you have lived or travelled in regions where fungal infections such as 

histoplasmosis, coccidioidomycosis or blastomycosis are endemic (found).  
 
• Tell your doctor if you have infections which keep coming back or other conditions that increase 

the risk of infections.  
 
• You should pay special attention to signs of infection while you are being treated with 

Amsparity. It is important to tell your doctor if you get symptoms of infections, such as fever, 
wounds, feeling tired or dental problems. 

 
Hepatitis B virus 
 
• Tell your doctor if you are a carrier of the hepatitis B virus (HBV), if you have active HBV 

infection or if you think you might be at risk of getting HBV. Your doctor should test you for 
HBV. Adalimumab can reactivate HBV infection 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 infection can be life-threatening.  

 
Age over 65 years 
 
• If you are over 65 years you may be more susceptible to infections while taking Amsparity. You 

and your doctor should pay special attention to signs of infection while you are being treated 
with Amsparity. It is important to tell your doctor if you get symptoms of infections, such as 
fever, wounds, feeling tired or dental problems.  

 
Surgery or dental procedures 
 
• If you are about to have surgery or dental procedures, tell your doctor that you are taking 

Amsparity. Your doctor may recommend temporarily stopping Amsparity.  
 
Demyelinating disease 
 
• If you have or develop 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 Amsparity. Tell your doctor immediately if you get symptoms like changes in your 
vision, weakness in your arms or legs or numbness or tingling in any part of your body.  

 
Vaccination 
 
• Certain vaccines contain living but weakened forms of disease-causing bacteria or viruses that 

may cause infections and should not be given during treatment with Amsparity. Check with your 



205 

doctor before you receive any vaccines. It is recommended that, if possible, children be given all 
the scheduled vaccinations for their age before they start treatment with Amsparity. If you 
receive Amsparity while you are pregnant, your baby may be at higher risk for getting an 
infection for up to about 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 
Amsparity use during your pregnancy so they can decide when your baby should receive any 
vaccine.  

 
Heart failure 
 
• It is important to tell your doctor if you have had or have a serious heart condition. If you have 

mild heart failure and you are being treated with Amsparity, your heart failure status must be 
closely monitored by your doctor. 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.  

 
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. If you develop a fever that does not go away, or you bruise or 
bleed very easily or look very pale, call your doctor right away. Your doctor may decide to stop 
treatment.  

 
Cancer 
 
• There have been very rare cases of certain kinds of cancer in children and adults taking 

adalimumab or other TNFα blockers. People with more serious rheumatoid arthritis who have 
had the disease for a long time may have a higher than average risk of getting lymphoma and 
leukaemia (cancers that affect blood cells and bone marrow). If you take Amsparity 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 adalimumab. Some of those 
patients were also treated with the medicines azathioprine or mercaptopurine. Tell your doctor if 
you are taking azathioprine or mercaptopurine with Amsparity. 

  
• In addition, cases of non-melanoma skin cancer have been observed in patients taking 

adalimumab. If new areas of damaged skin appear during or after treatment or if existing marks 
or areas of damage 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 TNFα 
blocker. If you have COPD, or are a heavy smoker, you should discuss with your doctor whether 
treatment with a TNFα blocker is appropriate for you.  

 
Autoimmune disease 
 
• On rare occasions, treatment with Amsparity 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 Amsparity  
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  
 
Amsparity can be taken together with methotrexate or certain disease-modifying anti-rheumatic agents 
(for example, sulfasalazine, hydroxychloroquine, leflunomide and injectable gold preparations), 
corticosteroids or pain medications including non-steroidal anti-inflammatory drugs (NSAIDs).  
 



206 

You should not take Amsparity with medicines containing the active substances anakinra or abatacept 
due to increased risk of serious infection. The combination of adalimumab as well as other 
TNF-antagonists and anakinra or abatacept is not recommended based upon the possible increased risk 
for infections, including serious infections and other potential pharmacological interactions. 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 Amsparity 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. 
 
Amsparity 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 adalimumab during pregnancy compared with mothers with the same disease who did not 
receive adalimumab. 
 
Amsparity can be used during breast-feeding. 
 
If you receive Amsparity 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 Amsparity 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  
 
Amsparity may have a small effect on your ability to drive, cycle or use machines. Room spinning 
sensation (vertigo) and vision disturbances may occur after taking Amsparity.  
 
Amsparity contains sodium 
 
This medicine contains less than 1 mmol of sodium (23 mg) per 0.8 ml dose, that is to say essentially 
‘sodium-free’. 
 
 
3. How to use Amsparity  
 
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 Amsparity if you need a 
different dose. 
 
Amsparity is injected under the skin (subcutaneous use). 
 
Adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or axial spondyloarthritis 
without radiographic evidence of ankylosing spondylitis 
 
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.  
 
In rheumatoid arthritis, methotrexate is continued while using Amsparity. If your doctor determines 
that methotrexate is inappropriate, Amsparity can be given alone.  
 



207 

If you have rheumatoid arthritis and you do not receive methotrexate with your Amsparity 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 Amsparity is 20 mg every other week.  
 
Children, adolescents and adults from 2 years of age weighing 30 kg or more 
 
The recommended dose of Amsparity 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 Amsparity is 20 mg every other week. 
 
Children, adolescents and adults from 6 years of age weighing 30 kg or more 
 
The recommended dose of Amsparity 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 Amsparity for as long as your doctor has told you. If this dose does not work 
well enough, 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 Amsparity 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 Amsparity 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 as 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.  
 
Adolescents with hidradenitis suppurativa from 12 to 17 years of age weighing 30 kg or more 
 
The recommended dose of Amsparity 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 this dose does not work well enough, 
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.  



208 

 
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 starting 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, and thereafter as 40 mg every other week. If this dose does not work well enough, 
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 to17 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 starting two weeks later.  
 
Thereafter, the usual dose is 20 mg every other week. If this dose does not work well enough, 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. If this dose does not work well enough, your 
doctor may increase the dosage to 40 mg every week or 80 mg every other week.  
 
Adults with ulcerative colitis  
 
The usual Amsparity dose for adults with ulcerative colitis is 160 mg initially (as four 40 mg injections 
in one day or as two 40 mg injections per day for two consecutive days), then 80 mg (as two 40 mg 
injections in one day) two weeks later, and then 40 mg every other week. If this dose does not work 
well enough, your doctor may increase the dosage to 40 mg every week or 80 mg every other week.  
 
Adults with non-infectious uveitis 
 
The usual dose for adults with non-infectious uveitis 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 Amsparity 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 Amsparity. Amsparity 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 Amsparity 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. 
 



209 

Children and adolescents from 2 years of age weighing 30 kg or more 
 
The usual dose of Amsparity 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  
 
Amsparity is administered by injection under the skin (by subcutaneous injection).  
 
Detailed instructions on how to inject Amsparity, the Instructions for Use, are provided at the 
end of this leaflet.  
 
If you use more Amsparity than you should  
 
If you accidentally inject Amsparity more frequently than you should, call your doctor or pharmacist 
and explain that you have taken more than required. Always take the outer carton of the medicine with 
you, even if it is empty.  
 
If you forget to use Amsparity 
 
If you forget to give yourself an injection, you should inject the next dose of Amsparity 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 Amsparity 
 
The decision to stop using Amsparity should be discussed with your doctor. Your symptoms may 
return upon stopping treatment.  
 
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 Amsparity injection.  
 
Seek medical attention urgently, if you notice any of the following signs: 
 
• 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 and symptoms of infection such as fever, feeling sick, wounds, dental problems, burning 

on urination, feeling weak or tired or coughing;  
• symptoms of nerve problems such as tingling, numbness, double vision, or arm or leg weakness;  
• signs of skin cancer such as a bump or open sore that does not heal;  
• signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, 

paleness.  
 



210 

The signs and symptoms described above can represent the side effects listed below, which have been 
observed with adalimumab: 
 
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 (belly) pain;  
• nausea and vomiting;  
• rash;  
• pain in the muscles or joints.  
 
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;  
• mouth 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;  
• symptoms of 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 room spinning);  
• sensation of heart beating rapidly;  
• high blood pressure;  
• flushing;  
• haematoma (a solid swelling with clotted blood);  
• 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;  



211 

• increased sweating;  
• hair loss;  
• new onset or worsening of psoriasis;  
• muscle spasms;  
• blood in urine;  
• kidney problems;  
• chest pain;  
• oedema (a build-up of fluid in the body which causes the affected tissue to swell);  
• fever;  
• reduction in blood platelets which increases risk of bleeding or bruising;  
• impaired healing.  
 
Uncommon (may affect up to 1 in 100 people) 
 
• opportunistic (unusual) 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, including cancer that affects the lymph system (lymphoma) and melanoma (a type of 

skin cancer);  
• immune disorders that could affect the lungs, skin and lymph nodes (most commonly as a 

condition called sarcoidosis);  
• vasculitis (inflammation of blood vessels);  
• tremor (shaking);  
• neuropathy (nerve damage);  
• stroke; 
• double vision;  
• 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 (build up of fat in liver cells);  
• night sweats;  
• scar;  
• abnormal muscle breakdown;  
• systemic lupus erythematosus (an immune disorder 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);  



212 

• severe allergic reaction with shock;  
• multiple sclerosis;  
• nerve disorders (such as inflammation of the optic nerve to the eye, and Guillain-Barré 

syndrome, a condition 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 wall of the gut);  
• hepatitis (liver inflammation);  
• reactivation of hepatitis B infection;  
• 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 (life-threatening reaction with flu-like symptoms and blistering 

rash);  
• facial oedema (swelling of the face) associated with allergic reactions;  
• erythema multiforme (inflammatory skin rash);  
• lupus-like syndrome; 
• angioedema (localised 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);  
• liver failure;  
• worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle 

weakness).  
 
Some side effects observed with adalimumab 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;  
• raised 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) 
 
• raised bilirubin measurement (liver blood test). 
 



213 

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 Amsparity  
 
Keep this medicine out of the sight and reach of children.  
 
Do not use this medicine after the expiry date which is 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 Amsparity pre-filled syringe may be 
stored at room temperature (up to 30°C) for a maximum period of 30 days – be sure to protect it from 
light. Once removed from the refrigerator for room temperature storage, the syringe must be used 
within 30 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 Amsparity contains  
 
The active substance is adalimumab.  
 
The other ingredients are L-histidine, L-histidine hydrochloride monohydrate, sucrose, edetate 
disodium dihydrate, L-methionine, polysorbate 80, and water for injections.  
 
What the Amsparity pre-filled syringe looks like and contents of the pack  
 
Amsparity 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 Amsparity pre-filled syringe is a glass syringe containing a clear, colourless to very light brown 
solution of adalimumab. Each pack contains 1, 2, 4 or 6 pre-filled syringes for patient use with 2 
(1 spare), 2, 4 or 6 alcohol pads, respectively.  
 
Not all pack sizes may be marketed.  
 
Amsparity may be available as a vial, a pre-filled syringe and/or a pre-filled pen.  
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


214 

Marketing Authorisation Holder  
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
Manufacturer  
 
Pfizer Service Company BVBA 
Hoge Wei 10 
Zaventem 1930 
Belgium 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder.  
 
België/Belgique/Belgien 
Luxembourg/Luxemburg 
Pfizer NV/SA 
Tél/Tel: +32 (0)2 554 62 11  

Kύπρος 
PFIZER EΛΛAΣ A.E. (CYPRUS BRANCH) 
Τηλ: +357 22 817690 
 

Česká Republika 
Pfizer, spol.  s r.o. 
Tel: +420-283-004-111 
 

Magyarország 
Pfizer Kft. 
Tel: +36 1 488 3700 
 

Danmark 
Pfizer ApS 
Tlf: +45 44 201 100 
 

Malta 
Drugsales Ltd  
Tel: +356 21 419070/1/2 
 

Deutchland: 
Pfizer Pharma PFE GmbH 
Tel: +49 (0)800 8535555 
 

Nederland 
Pfizer bv 
Tel: +31 (0)10 406 43 01 
 

България 
Пфайзер Люксембург САРЛ, 
Клон България 
Teл: +359 2 970 4333 
 

Norge 
Pfizer AS 
Tlf: +47 67 52 61 00 
 

Eesti 
Pfizer Luxembourg SARL Eesti filiaal 
Tel: +372 666 7500 
 

Österreich 
Pfizer Corporation Austria Ges.m.b.H. 
Tel: +43 (0)1 521 15-0 
 

Ελλάδα 
PFIZER EΛΛAΣ A.E. 
Τηλ.: +30 210 67 85 800 
 

Polska 
Pfizer Polska Sp. z o.o. 
Tel.: +48 22 335 61 00 
 

España 
Pfizer S.L. 
Tel: +34 91 490 99 00 
 
 

Portugal 
Laboratórios Pfizer, Lda. 
Tel: +351 21 423 5500 

France 
Pfizer  
Tél: +33 (0)1 58 07 34 40 
 

România 
Pfizer România S.R.L 
Tel: +40 (0) 21 207 28 00 
 



215 

Hrvatska 
Pfizer Croatia d.o.o. 
Tel: +385 1 3908 777 
 

Slovenija 
Pfizer Luxembourg SARL, Pfizer, podružnica 
za svetovanje s področja farmacevtske 
dejavnosti, Ljubljana 
Tel: +386 (0)1 52 11 400 
 

Ireland 
Pfizer Healthcare Ireland 
Tel: +1800 633 363 (toll free) 
Tel: +44 (0)1304 616161 
 

Slovenská Republika 
Pfizer Luxembourg SARL, organizačná zložka 
Tel: +421 2 3355 5500 
 

Ísland 
Icepharma hf. 
Tel: +354 540 8000 
 

Suomi/Finland 
Pfizer PFE Finland Oy 
Puh/Tel: +358 (0)9 430 040 
 
 

Italia 
Pfizer Italia S.r.l.  
Tel: +39 06 33 18 21 
 

Sverige 
Pfizer AB 
Tel: +46 (0)8 550 520 00 
 

Latvija 
Pfizer Luxembourg SARL filiāle Latvijā 
Tel. +371 67035775 
 

United Kingdom 
Pfizer Limited 
Tel: +44 (0)1304 616161 
 

Lietuva 
Pfizer Luxembourg SARL filialas Lietuvoje 
Tel. +3705 2514000 

 

 
 
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. 
 

http://www.ema.europa.eu/
http://www.ema.europa.eu/


216 

INSTRUCTIONS FOR USE 
Amsparity (adalimumab) 

40 mg 
Single-dose Pre-filled Syringe, for subcutaneous injection 

 
Keep this leaflet. These instructions show step-by-step how to prepare and give an injection.  
Store your Amsparity pre-filled syringe in the refrigerator between 2°C to 8°C.  
Store Amsparity pre-filled syringe in the original carton until use to protect from direct sunlight. 
If needed, for example when you are traveling, you may store Amsparity pre-filled syringe at 
room temperature up to 30°C for up to 30 days. 
Keep Amsparity, injection supplies, and all other medicines out of the reach of children. 
 
 
Amsparity for injection comes in a disposable single use pre-filled syringe that contains a single dose 
of medicine. 
Do not try to inject Amsparity yourself until you have read and understood the Instructions for Use. If 
your doctor, nurse or pharmacist decides that you or a caregiver may be able to give your injections of 
Amsparity at home, you should receive training on the correct way to prepare and inject Amsparity. 
It is also important to talk to your doctor, nurse or pharmacist to be sure you understand your 
Amsparity dosing instructions. To help you remember when to inject Amsparity, you can mark your 
calendar ahead of time. Talk to your doctor, nurse or pharmacist if you or your caregiver have any 
questions about the correct way to inject Amsparity. 
After proper training, Amsparity for injection can be self-administered or given by a caregiver. 

 
1. Supplies you need 
 
• You will need the following supplies for each injection of Amsparity. Find a clean, flat surface 

to place the supplies on. 
o 1 Amsparity pre-filled syringe in a tray, inside the carton 
o 1 alcohol swab, inside the carton 
o 1 cotton ball or gauze pad (not included in your Amsparity carton) 
o A suitable sharps container (not included in your Amsparity carton). 
Important: If you have any questions about your Amsparity pre-filled syringe or medicine, talk 
to your doctor, nurse or pharmacist. 

 

 
 
 
2. Getting ready 
 
• Remove Amsparity carton from the refrigerator. 
• Open the carton and take out the tray containing your pre-filled syringe. 



217 

• Check your carton and tray; do not use if: 
o the expiration date has passed 
o it has been frozen or thawed 
o it has been dropped, even if it looks undamaged 
o it has been out of the refrigerator for more than 30 days 
o it appears to be damaged 
o the seals on a new carton are broken. 

• If any of the above apply, dispose of your pre-filled syringe in the same way as a used syringe. 
You will need a new pre-filled syringe to give your injection. 

• Wash your hands with soap and water, and dry completely.  
If you have any questions about your medicine, please talk to your doctor, nurse or pharmacist. 

 
 

 
 
 
• Peel back the paper seal on the tray. 
• Remove 1 pre-filled syringe from the tray and put the original carton with any unused pre-filled 

syringes back in the refrigerator. 
• Do not use your syringe if it appears to be damaged. 
• Your pre-filled syringe may be used straight from the refrigerator. 
• You may find that using your pre-filled syringe at room temperature reduces stinging or 

discomfort. Leave your pre-filled syringe at room temperature away from direct sunlight for 15 
to 30 minutes before your injection. 

• Do not remove the needle cover from your pre-filled syringe until you are ready to inject. 
Always hold the pre-filled syringe by the syringe barrel to prevent damage. 

 
 



218 

 
 
 
• Look carefully at your medicine in the window.  
• Gently tilt your pre-filled syringe back and forth to check the medicine. 
• Do not shake your pre-filled syringe. Shaking can damage your medicine. 
• Make sure the medicine in the pre-filled syringe is clear and colourless to very light brown and 

free from flakes or particles. It is normal to see one or more air bubbles in the window. Do not 
attempt to remove air bubbles. 
If you have any questions about your medicine, please talk to your doctor, nurse or pharmacist.  

 
 

 
 
 
• Choose a different site each time you give yourself an injection. 
• Do not inject into bony areas or areas on your skin that are bruised, red, sore (tender) or hard. 

Avoid injecting into areas with scars or stretch marks. 
o If you have psoriasis, do not inject directly into any raised, thick, red, or scaly skin 

patches or lesions on your skin. 
• Do not inject through your clothes. 
• Wipe the injection site with the alcohol swab. 
• Allow the injection site to dry. 
 
 



219 

 
 
 
• Hold the pre-filled syringe by the syringe barrel. Carefully pull the needle cover straight off and 

away from your body when you are ready to inject. 
• It is normal to see a few drops of medicine at the needle tip when you remove the needle cover. 
• Throw the needle cover away into a sharps disposal container. 

Note: Be careful when you handle your pre-filled syringe to avoid an accidental needle stick 
injury. 

 
 

 
 
 
• Gently pinch up a fold of skin in the cleaned injection site area. 
• Insert the needle to its full depth into the skin, at a 45 degree angle, as shown.  
• After the needle is inserted, release the pinched skin. 

Important: Do not re-insert the needle into your skin. If the needle has already been inserted 
into the skin and you change your mind about where to inject, you will need a replacement 
pre-filled syringe. 

 
 



220 

 
 
 

• Using slow and constant pressure, push the plunger rod all the way down until the barrel is 
empty. It usually takes 2 to 5 seconds to deliver the dose. 
Note: It is recommended to hold your pre-filled syringe in the skin for an additional 5 seconds 
after the plunger has been pressed down completely. 

• Pull the needle out of the skin at the same angle at which it entered. 
 
 

 
 
 

• Check that your medicine has completely emptied from your pre-filled syringe. 
• Never re-insert the needle. 
• Never re-cap the needle. 

Note: If the grey stopper is not in the position shown, you may not have injected all of your 
medicine. Talk to your doctor, nurse or pharmacist right away. 

 
 



221 

 
 
 
• Dispose of the syringe straight away as instructed by your doctor, nurse or pharmacist and in 

accordance with local health and safety laws. 
 
 

 
 
 
• Look closely at your injection site. If there is blood, use a clean cotton ball or gauze pad to press 

lightly on the injection area for a few seconds.  
• Do not rub the site. 

Note: Store any unused syringes in the refrigerator in the original carton. 
 
 
See over for 
Package leaflet: Information for the patient 
 
 



222 

 
Package leaflet: Information for the patient 

 
Amsparity 40 mg solution for injection in pre-filled pen 

adalimumab 
 
 

 
 
 

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
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 Amsparity and during treatment 
with Amsparity. 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 Amsparity is and what it is used for  
2. What you need to know before you use Amsparity  
3. How to use Amsparity  
4. Possible side effects  
5. How to store Amsparity  
6. Contents of the pack and other information  
 
 
1. What Amsparity is and what it is used for  
 
Amsparity contains the active substance adalimumab, a medicine that acts on your body’s immune 
(defence) system. 
 
Amsparity is intended for the treatment of the following inflammatory diseases: 
• rheumatoid arthritis,  
• polyarticular juvenile idiopathic arthritis,  
• paediatric enthesitis-related arthritis,  
• ankylosing spondylitis,  
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis,  
• psoriatic arthritis,  
• psoriasis,  
• hidradenitis suppurativa,  
• Crohn’s disease,  



223 

• ulcerative colitis and  
• non-infectious uveitis.  
 
The active ingredient in Amsparity, adalimumab, is a monoclonal antibody. Monoclonal antibodies are 
proteins that attach to a specific target in the body.  
 
The target of adalimumab is another 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, Amsparity blocks its action and reduces the inflammation in these 
diseases. 
 
Rheumatoid arthritis  
 
Rheumatoid arthritis is an inflammatory disease of the joints.  
 
Amsparity 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 these medicines do not work well enough, you will be given Amsparity to treat your rheumatoid 
arthritis.  
 
Amsparity can also be used to treat severe, active and progressive rheumatoid arthritis without 
previous methotrexate treatment.  
 
Amsparity can slow down the damage to the cartilage and bone of the joints caused by the disease and 
improve physical function.  
 
Usually, Amsparity is used with methotrexate. If your doctor considers that methotrexate is 
inappropriate, Amsparity can be given alone.  
 
Polyarticular juvenile idiopathic arthritis 
 
Polyarticular juvenile idiopathic arthritis is an inflammatory disease of the joints that usually first 
appears in childhood.  
 
Amsparity is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged 
2 to 17 years. Patients may first be given other disease-modifying medicines, such as methotrexate. If 
these medicines do not work well enough, patients will be given Amsparity to treat their polyarticular 
juvenile idiopathic arthritis.  
 
Paediatric enthesitis-related arthritis 
 
Paediatric enthesitis-related arthritis is an inflammatory disease of the joints and the places where 
tendons join the bone. 
 
Amsparity is used to treat enthesitis-related arthritis in children and adolescents aged 6 to 17 years. 
Patients may first be given other disease-modifying medicines, such as methotrexate. If these 
medicines do not work well enough, patients will be given Amsparity to treat their 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.  
 
Amsparity is used in adults to treat these conditions. If you have ankylosing spondylitis or axial 
spondyloarthritis without radiographic evidence of ankylosing spondylitis, you will first be given other 



224 

medicines. If these medicines do not work well enough, you will be given Amsparity to reduce the 
signs and symptoms of your disease.  
 
Psoriatic arthritis  
 
Psoriatic arthritis is an inflammation of the joints associated with psoriasis.  
 
Amsparity is used to treat psoriatic arthritis in adults. Amsparity can 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 an inflammatory 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.  
 
Amsparity is used to treat moderate to severe plaque psoriasis in adults. Amsparity is also used to treat 
severe plaque psoriasis in children and adolescents aged 4 to 17 years for whom medicines applied to 
the skin and treatment with UV light have either not worked very well or are not suitable.  
 
Hidradenitis suppurativa in adults and adolescents  
 
Hidradenitis suppurativa (sometimes called acne inversa) is a long-term 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.  
 
Amsparity is used to treat hidradenitis suppurativa in adults and adolescents from 12 years of age. 
Amsparity 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 these medicines do not work 
well enough, you will be given Amsparity.  
 
Crohn’s disease in adults and children  
 
Crohn’s disease is an inflammatory disease of the gut.  
 
Amsparity 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 Amsparity to reduce the signs and symptoms of your Crohn’s 
disease.  
 
Ulcerative colitis  
 
Ulcerative colitis is an inflammatory disease of the bowel.  
 
Amsparity is used to treat ulcerative colitis in adults. If you have ulcerative colitis you will first be 
given other medicines. If these medicines do not work well enough, you will be given Amsparity 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. 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). Amsparity works by reducing this inflammation. 



225 

 
Amsparity 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.  
 
You may first be given other medicines. If these medicines do not work well enough, you will be 
given Amsparity to reduce the signs and symptoms of your disease. 
 
 
2. What you need to know before you use Amsparity  
 
Do not use Amsparity  
 
• if you are allergic to adalimumab or any of the other ingredients of this medicine (listed in 

section 6).  
 

• if you have a severe infection, including active tuberculosis, sepsis (blood poisoning) or 
opportunistic infections (unusual infections associated with a weakened immune system). It is 
important that you tell your doctor if you have symptoms of infections, for example, fever, 
wounds, feeling tired, dental problems (see “Warnings and precautions”).  
 

• 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 Amsparity.  
 
It is important that you and your doctor record the brand name and batch number of your medication. 
 
Allergic reactions 
 
• If you have allergic reactions with symptoms such as chest tightness, wheezing, dizziness, 

swelling or rash, do not inject more Amsparity 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 Amsparity. If you are unsure, 
contact your doctor.  

 
• You might get infections more easily while you are receiving Amsparity 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, or other opportunistic 
infections (unusual infectious organisms) and sepsis (blood poisoning). In rare cases, these 
infections may 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 temporarily 
stopping Amsparity.  

 
Tuberculosis (TB) 
 
• As cases of tuberculosis have been reported in patients treated with adalimumab, your doctor 

will check you for signs and symptoms of tuberculosis before starting Amsparity. This will 
include a thorough medical evaluation including your medical history and screening tests (for 



226 

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 had preventative treatment for 

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.  

 
Travel / recurrent infection 
 
• Tell your doctor if you have lived or travelled in regions where fungal infections such as 

histoplasmosis, coccidioidomycosis or blastomycosis are endemic (found).  
 
• Tell your doctor if you have infections which keep coming back or other conditions that increase 

the risk of infections.  
 
• You should pay special attention to signs of infection while you are being treated with 

Amsparity. It is important to tell your doctor if you get symptoms of infections, such as fever, 
wounds, feeling tired or dental problems. 

 
Hepatitis B virus 
 
• Tell your doctor if you are a carrier of the hepatitis B virus (HBV), if you have active HBV 

infection or if you think you might be at risk of getting HBV. Your doctor should test you for 
HBV. Adalimumab can reactivate HBV infection 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 infection can be life-threatening.  

 
Age over 65 years 
 
• If you are over 65 years you may be more susceptible to infections while taking Amsparity. You 

and your doctor should pay special attention to signs of infection while you are being treated 
with Amsparity. It is important to tell your doctor if you get symptoms of infections, such as 
fever, wounds, feeling tired or dental problems.  

 
Surgery or dental procedures 
 
• If you are about to have surgery or dental procedures, tell your doctor that you are taking 

Amsparity. Your doctor may recommend temporarily stopping Amsparity.  
 
Demyelinating disease 
 
• If you have or develop 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 Amsparity. Tell your doctor immediately if you get symptoms like changes in your 
vision, weakness in your arms or legs or numbness or tingling in any part of your body.  

 
Vaccination 
 
• Certain vaccines contain living but weakened forms of disease-causing bacteria or viruses that 

may cause infections and should not be given during treatment with Amsparity. Check with your 



227 

doctor before you receive any vaccines. It is recommended that, if possible, children be given all 
the scheduled vaccinations for their age before they start treatment with Amsparity. If you 
receive Amsparity while you are pregnant, your baby may be at higher risk for getting an 
infection for up to about 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 
Amsparity use during your pregnancy so they can decide when your baby should receive any 
vaccine.  

 
Heart failure 
 
• It is important to tell your doctor if you have had or have a serious heart condition. If you have 

mild heart failure and you are being treated with Amsparity, your heart failure status must be 
closely monitored by your doctor. 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.  

 
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. If you develop a fever that does not go away, or you bruise or 
bleed very easily or look very pale, call your doctor right away. Your doctor may decide to stop 
treatment.  

 
Cancer 
 
• There have been very rare cases of certain kinds of cancer in children and adults taking 

adalimumab or other TNFα blockers. People with more serious rheumatoid arthritis who have 
had the disease for a long time may have a higher than average risk of getting lymphoma and 
leukaemia (cancers that affect blood cells and bone marrow). If you take Amsparity 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 adalimumab. Some of those 
patients were also treated with the medicines azathioprine or mercaptopurine. Tell your doctor if 
you are taking azathioprine or mercaptopurine with Amsparity.  

 
• In addition, cases of non-melanoma skin cancer have been observed in patients taking 

adalimumab. If new areas of damaged skin appear during or after treatment or if existing marks 
or areas of damage 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 TNFα 
blocker. If you have COPD, or are a heavy smoker, you should discuss with your doctor whether 
treatment with a TNFα blocker is appropriate for you.  

 
Autoimmune disease 
 
• On rare occasions, treatment with Amsparity 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 Amsparity  
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  
 
Amsparity can be taken together with methotrexate or certain disease-modifying anti-rheumatic agents 
(for example, sulfasalazine, hydroxychloroquine, leflunomide and injectable gold preparations), 
corticosteroids or pain medications including non-steroidal anti-inflammatory drugs (NSAIDs).  
 



228 

You should not take Amsparity with medicines containing the active substances anakinra or abatacept 
due to increased risk of serious infection. The combination of adalimumab as well as other 
TNF-antagonists and anakinra or abatacept is not recommended based upon the possible increased risk 
for infections, including serious infections and other potential pharmacological interactions. 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 Amsparity 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. 
 
Amsparity 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 adalimumab during pregnancy compared with mothers with the same disease who did not 
receive adalimumab. 
 
Amsparity can be used during breast-feeding. 
 
If you receive Amsparity 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 Amsparity 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  
 
Amsparity may have a small effect on your ability to drive, cycle or use machines. Room spinning 
sensation (vertigo) and vision disturbances may occur after taking Amsparity.  
 
Amsparity contains sodium 
 
This medicine contains less than 1 mmol of sodium (23 mg) per 0.8 ml dose, that is to say essentially 
‘sodium-free’. 
 
 
3. How to use Amsparity  
 
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 Amsparity if you need a 
different dose. 
 
Amsparity is injected under the skin (subcutaneous use). 
 
Adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or axial spondyloarthritis 
without radiographic evidence of ankylosing spondylitis 
 
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.  
 
In rheumatoid arthritis, methotrexate is continued while using Amsparity. If your doctor determines 
that methotrexate is inappropriate, Amsparity can be given alone.  
 



229 

If you have rheumatoid arthritis and you do not receive methotrexate with your Amsparity 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 Amsparity is 20 mg every other week.  
 
Children, adolescents and adults from 2 years of age weighing 30 kg or more 
 
The recommended dose of Amsparity 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 Amsparity is 20 mg every other week. 
 
Children, adolescents and adults from 6 years of age weighing 30 kg or more 
 
The recommended dose of Amsparity 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 Amsparity for as long as your doctor has told you. If this dose does not work 
well enough, 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 Amsparity 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 Amsparity 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 as 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.  
 
Adolescents with hidradenitis suppurativa from 12 to 17 years of age weighing 30 kg or more  
 
The recommended dose of Amsparity 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 this dose does not work well enough, 
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.  



230 

 
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 starting 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, and thereafter as 40 mg every other week. If this dose does not work well enough, 
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 to17 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 starting two weeks later.  
 
Thereafter, the usual dose is 20 mg every other week. If this dose does not work well enough, 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. If this dose does not work well enough, your 
doctor may increase the dosage to 40 mg every week or 80 mg every other week.  
 
Adults with ulcerative colitis 
 
The usual Amsparity dose for adults with ulcerative colitis is 160 mg initially (as four 40 mg injections 
in one day or as two 40 mg injections per day for two consecutive days), then 80 mg (as two 40 mg 
injections in one day) two weeks later, and then 40 mg every other week. If this dose does not work 
well enough, your doctor may increase the dosage to 40 mg every week or 80 mg every other week.  
 
Adults with non-infectious uveitis 
 
The usual dose for adults with non-infectious uveitis 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 Amsparity 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 Amsparity. Amsparity 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 Amsparity 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. 
 



231 

Children and adolescents from 2 years of age weighing 30 kg or more 
 
The usual dose of Amsparity 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  
 
Amsparity is administered by injection under the skin (by subcutaneous injection).  
 
Detailed instructions on how to inject Amsparity, the Instructions for Use, are provided at the 
end of this leaflet.  
 
If you use more Amsparity than you should 
 
If you accidentally inject Amsparity more frequently than you should, call your doctor or pharmacist 
and explain that you have taken more than required. Always take the outer carton of the medicine with 
you, even if it is empty.  
 
If you forget to use Amsparity 
 
If you forget to give yourself an injection, you should inject the next dose of Amsparity 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 Amsparity 
 
The decision to stop using Amsparity should be discussed with your doctor. Your symptoms may 
return upon stopping treatment.  
 
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 Amsparity injection.  
 
Seek medical attention urgently, if you notice any of the following signs: 
 
• 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 and symptoms of infection such as fever, feeling sick, wounds, dental problems, burning 

on urination, feeling weak or tired or coughing;  
• symptoms of nerve problems such as tingling, numbness, double vision, or arm or leg weakness;  
• signs of skin cancer such as a bump or open sore that does not heal;  
• signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, 

paleness  
 



232 

The signs and symptoms described above can represent the side effects listed below, which have been 
observed with adalimumab:  
 
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 (belly) pain;  
• nausea and vomiting;  
• rash;  
• pain in the muscles or joints.  

 
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;  
• mouth 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;  
• symptoms of 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 room spinning);  
• sensation of heart beating rapidly;  
• high blood pressure;  
• flushing;  
• haematoma (a solid swelling with clotted blood);  
• 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;  



233 

• increased sweating;  
• hair loss;  
• new onset or worsening of psoriasis;  
• muscle spasms;  
• blood in urine;  
• kidney problems;  
• chest pain;  
• oedema (a build-up of fluid in the body which causes the affected tissue to swell);  
• fever;  
• reduction in blood platelets which increases risk of bleeding or bruising;  
• impaired healing.  
 
Uncommon (may affect up to 1 in 100 people) 
 
• opportunistic (unusual) 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, including cancer that affects the lymph system (lymphoma) and melanoma (a type of 

skin cancer);  
• immune disorders that could affect the lungs, skin and lymph nodes (most commonly as a 

condition called sarcoidosis);  
• vasculitis (inflammation of blood vessels);  
• tremor (shaking);  
• neuropathy (nerve damage);  
• stroke; 
• double vision;  
• 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 (build up of fat in liver cells);  
• night sweats;  
• scar;  
• abnormal muscle breakdown;  
• systemic lupus erythematosus (an immune disorder 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);  



234 

• severe allergic reaction with shock;  
• multiple sclerosis;  
• nerve disorders (such as inflammation of the optic nerve to the eye, and Guillain-Barré 

syndrome, a condition 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 wall of the gut);  
• hepatitis (liver inflammation);  
• reactivation of hepatitis B infection;  
• 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 (life-threatening reaction with flu-like symptoms and blistering 

rash);  
• facial oedema (swelling of the face) associated with allergic reactions;  
• erythema multiforme (inflammatory skin rash);  
• lupus-like syndrome; 
• angioedema (localised 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);  
• liver failure;  
• worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle 

weakness).  
 
Some side effects observed with adalimumab 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;  
• raised 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) 
 
• raised bilirubin measurement (liver blood test). 
 



235 

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 Amsparity  
 
Keep this medicine out of the sight and reach of children.  
 
Do not use this medicine after the expiry date which is stated on the label / 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 Amsparity pre-filled pen may be stored 
at room temperature (up to 30°C) for a maximum period of 30 days – be sure to protect it from light. 
Once removed from the refrigerator for room temperature storage, the pen must be used within 
30 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 Amsparity contains 
 
The active substance is adalimumab.  
 
The other ingredients are L-histidine, L-histidine hydrochloride monohydrate, sucrose, edetate 
disodium dihydrate, L-methionine, polysorbate 80, and water for injections. 
 
What the Amsparity pre-filled pen looks like and contents of the pack  
 
Amsparity 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 Amsparity pre-filled pen contains a clear, colourless to very light brown solution of adalimumab.  
 
Each pack contains 1, 2, 4 or 6 pre-filled pens for patient use with 2 (1 spare), 2, 4 or 6 alcohol pads, 
respectively. 
 
Not all pack sizes may be marketed.  
 
Amsparity may be available as a vial, a pre-filled syringe and/or a pre-filled pen.  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


236 

 
Marketing Authorisation Holder  
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
Manufacturer  
 
Pfizer Service Company BVBA 
Hoge Wei 10 
Zaventem 1930 
Belgium 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder.  
 
België/Belgique/Belgien 
Luxembourg/Luxemburg 
Pfizer NV/SA 
Tél/Tel: +32 (0)2 554 62 11  

Kύπρος 
PFIZER EΛΛAΣ A.E. (CYPRUS BRANCH) 
Τηλ: +357 22 817690 
 

Česká Republika 
Pfizer, spol.  s r.o. 
Tel: +420-283-004-111 
 

Magyarország 
Pfizer Kft. 
Tel: +36 1 488 3700 
 

Danmark 
Pfizer ApS 
Tlf: +45 44 201 100 
 

Malta 
Drugsales Ltd  
Tel: +356 21 419070/1/2 
 

Deutchland: 
Pfizer Pharma PFE GmbH 
Tel: +49 (0)800 8535555 
 

Nederland 
Pfizer bv 
Tel: +31 (0)10 406 43 01 
 

България 
Пфайзер Люксембург САРЛ, 
Клон България 
Teл: +359 2 970 4333 
 

Norge 
Pfizer AS 
Tlf: +47 67 52 61 00 
 

Eesti 
Pfizer Luxembourg SARL Eesti filiaal 
Tel: +372 666 7500 
 

Österreich 
Pfizer Corporation Austria Ges.m.b.H. 
Tel: +43 (0)1 521 15-0 
 

Ελλάδα 
PFIZER EΛΛAΣ A.E. 
Τηλ.: +30 210 67 85 800 
 

Polska 
Pfizer Polska Sp. z o.o. 
Tel.: +48 22 335 61 00 
 

España 
Pfizer S.L. 
Tel: +34 91 490 99 00 
 
 

Portugal 
Laboratórios Pfizer, Lda. 
Tel: +351 21 423 5500 

France 
Pfizer  
Tél: +33 (0)1 58 07 34 40 
 

România 
Pfizer România S.R.L 
Tel: +40 (0) 21 207 28 00 
 



237 

Hrvatska 
Pfizer Croatia d.o.o. 
Tel: +385 1 3908 777 
 

Slovenija 
Pfizer Luxembourg SARL, Pfizer, podružnica 
za svetovanje s področja farmacevtske 
dejavnosti, Ljubljana 
Tel: +386 (0)1 52 11 400 
 

Ireland 
Pfizer Healthcare Ireland 
Tel: +1800 633 363 (toll free) 
Tel: +44 (0)1304 616161 
 

Slovenská Republika 
Pfizer Luxembourg SARL, organizačná zložka 
Tel: +421 2 3355 5500 
 

Ísland 
Icepharma hf. 
Tel: +354 540 8000 
 

Suomi/Finland 
Pfizer PFE Finland Oy 
Puh/Tel: +358 (0)9 430 040 
 
 

Italia 
Pfizer Italia S.r.l.  
Tel: +39 06 33 18 21 
 

Sverige 
Pfizer AB 
Tel: +46 (0)8 550 520 00 
 

Latvija 
Pfizer Luxembourg SARL filiāle Latvijā 
Tel. +371 67035775 
 

United Kingdom 
Pfizer Limited 
Tel: +44 (0)1304 616161 
 

Lietuva 
Pfizer Luxembourg SARL filialas Lietuvoje 
Tel. +3705 2514000 

 

 
 
 
 
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.  
 

http://www.ema.europa.eu/
http://www.ema.europa.eu/


238 

INSTRUCTIONS FOR USE 
Amsparity (adalimumab) Single-dose Pre-filled Pen 

40 mg 
for subcutaneous injection  

 
Keep this leaflet. These instructions show step-by-step how to prepare and give an injection.  
Store your Amsparity pen in the refrigerator between 2°C to 8°C.  
Store Amsparity pen in the original carton until use to protect from direct sunlight. 
If needed, for example when you are traveling, you may store Amsparity pen at room 
temperature up to 30°C for up to 30 days. 
Keep Amsparity, injection supplies, and all other medicines out of the reach of children. 
 
 
Amsparity for injection comes in a disposable single use pen that contains a single dose of medicine. 
Do not try to inject Amsparity yourself until you have read and understood the Instructions for Use. If 
your doctor, nurse or pharmacist decides that you or a caregiver may be able to give your injections of 
Amsparity at home, you should receive training on the correct way to prepare and inject Amsparity. 
It is also important to talk to your doctor, nurse or pharmacist to be sure you understand your 
Amsparity dosing instructions. To help you remember when to inject Amsparity, you can mark your 
calendar ahead of time. Talk to your doctor, nurse or pharmacist if you or your caregiver have any 
questions about the correct way to inject Amsparity. 
After proper training, Amsparity for injection can be self-administered or given by a caregiver. 
 
1. Supplies you need 

 
• You will need the following supplies for each injection of Amsparity. Find a clean, flat surface 

to place the supplies on. 
o 1 Amsparity pen, inside the carton 
o 1 alcohol swab, inside the carton 
o 1 cotton ball or gauze pad (not included in your Amsparity carton) 
o A suitable sharps container (not included in your Amsparity carton). 
Important: If you have any questions about your Amsparity pen or medicine, talk to your 
doctor, nurse or pharmacist. 

 
2. Getting ready 
 
• Remove the Amsparity carton from the refrigerator. 
• Take out 1 Amsparity pen and the alcohol swab. Keep your pen out of direct sunlight. Put the 

original carton with any unused pens back in the refrigerator. 
• Do not use your pen if: 

o your pen or the carton containing the pen has been dropped, even if it looks undamaged 
o it has been frozen or thawed 
o it appears to be damaged  
o the seals on a new carton are broken 
o it has been out of the refrigerator for more than 30 days 
o the expiration date has passed. 

• If any of the above apply, dispose of your pen in the same way as a used pen. You will need a 
new pen to give your injection. 

• Your pen may be used straight from the refrigerator. 
• You may find that using your pen at room temperature reduces stinging or discomfort. Leave 

your pen at room temperature away from direct sunlight for 15 to 30 minutes before your 
injection. 

• Wash your hands with soap and water, and dry completely.  
• Do not remove the cap until you are ready to inject.  

 
 



239 

 
 
 
 
 

 
 

• Look carefully at your medicine in the window.  
• Gently tilt your pen back and forth to check the medicine.  
• Do not shake your pen. Shaking can damage your medicine. 
• Make sure the medicine in the pen is clear and colourless to very light brown and free from 

flakes or particles. It is normal to see one or more air bubbles in the window. Do not attempt to 
remove air bubbles. 
If you have any questions about your medicine, please talk to your doctor, nurse or pharmacist. 

 
 

 
 
 

• Choose a different site each time you give yourself an injection. 



240 

• Do not inject into bony areas or areas on your skin that are bruised, red, sore (tender) or hard. 
Avoid injecting into areas with scars or stretch marks. 
o If you have psoriasis, do not inject directly into any raised, thick, red, or scaly skin 

patches or lesions on your skin. 
• Do not inject through your clothes. 
• Wipe the injection site with the alcohol swab. 
• Allow the injection site to dry. 

 
 

 
 
 

• Twist and pull off the cap.  
• Throw the cap away into a sharps disposal container; it is not needed again. 
• It is normal to see a few drops of medicine at the needle tip when you remove the cap. 

Caution: Handle your pen with care to avoid an accidental needle stick injury. 
Note: The needle cover stays inside the cap after removal. 

 
 

 
 
 

• Push your pen firmly against the skin at 90 degrees, as shown. 
Note: The needle goes into the skin as you push your pen down. The injection button will 
unlock when you are pushing the pen down firmly enough. 

• Keep your pen pushed against the skin until Step 8. 
Note: Do not re-insert the needle into your skin if you change your mind about where to inject. 
You will need a replacement pen if the needle has already been inserted into the skin. 



241 

 
 

 
 
 

• Press the injection button all the way down and you will hear a click. You may take your finger 
off the injection button when the injection has started. 

• Keep holding your pen firmly against the skin while the orange bar moves across the window. 
This usually takes 3 to 10 seconds to deliver the dose. 

• Wait for at least 5 more seconds after the 2nd click to allow the medicine to be absorbed. 
Note: If you cannot press down the injection button, it is because you are not pushing the pen 
down firmly enough. Take your finger off the injection button and push your pen down more 
firmly against the skin. Then try pushing the button again. If this does not work, stretching or 
pinching the skin may make the injection site firmer, making pressing the injection button 
easier. 

 
 

 
 
 

• Do not remove your pen until you have waited at least 5 seconds after the 2nd click.  
• Remove your pen from the skin. 

Note: After you remove your pen from the skin, the needle will be automatically covered. 
• If you see more than a small drop of medicine on the skin after your injection, next time you 

inject wait a little longer to remove the pen from the skin. 
 
 



242 

 
 
 

• You should see an orange bar in the window. 
• If the window has not turned orange, or if it looks like the medicine is still injecting, this means 

you have not received a full dose. Talk to your doctor, nurse or pharmacist right away. 
• Do not inject another dose. 

 
 

 
 
 

• Dispose of the pen straight away as instructed by your doctor, nurse or pharmacist and in 
accordance with local health and safety laws. 

 
 



243 

 
 
 

• Look closely at your injection site. If there is blood, use a clean cotton ball or gauze pad to press 
lightly on the injection area for a few seconds.  

• Do not rub the injection site. 
Note: Store any unused pens in the refrigerator in the original carton. 

 
 
See over for 
Package leaflet: Information for the patient 
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER 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
	A. LABELLING
	B. PACKAGE LEAFLET