Cimzia

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in pre-filled syringe 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each pre-filled syringe contains 200 mg certolizumab pegol in one ml. 
 
Certolizumab pegol is a recombinant, humanised antibody Fab' fragment against tumour necrosis 
factor alpha (TNFα) expressed in Escherichia coli and conjugated to polyethylene glycol (PEG). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection (injection). 
 
Clear to opalescent, colourless to yellow solution. The pH of the solution is approximately 4.7. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Rheumatoid arthritis 
Cimzia, in combination with methotrexate (MTX), is indicated for: 
 the treatment of moderate to severe, active rheumatoid arthritis (RA) in adult patients when the 

response to disease-modifying antirheumatic drugs (DMARDs) including MTX, has been 
inadequate. Cimzia can be given as monotherapy in case of intolerance to MTX or when 
continued treatment with MTX is inappropriate 

 
 the treatment of severe, active and progressive RA in adults not previously treated with MTX or 

other DMARDs. 
 
Cimzia 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 MTX. 
 
Axial spondyloarthritis 
Cimzia is indicated for the treatment of adult patients with severe active axial spondyloarthritis, 
comprising:  
 
Ankylosing spondylitis (AS) (also known as radiographic axial spondyloarthritis) 
Adults with severe active ankylosing spondylitis who have had an inadequate response to, or are 
intolerant to nonsteroidal anti-inflammatory drugs (NSAIDs).  

 
Axial spondyloarthritis without radiographic evidence of AS (also known as non-radiographic axial 
spondyloarthritis) 
Adults with severe active axial spondyloarthritis without radiographic evidence of AS but with 
objective signs of inflammation by elevated C-reactive protein (CRP) and /or magnetic resonance 
imaging (MRI), who have had an inadequate response to, or are intolerant to NSAIDs. 
 
Psoriatic arthritis  
Cimzia, in combination with MTX, is indicated for the treatment of active psoriatic arthritis in adults 
when the response to previous DMARD therapy has been inadequate. 
 



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Cimzia can be given as monotherapy in case of intolerance to methotrexate or when continued 
treatment with methotrexate is inappropriate. 
 
Plaque psoriasis 
Cimzia is indicated for the treatment of moderate to severe plaque psoriasis in adults who are 
candidates for systemic therapy. 
 
For details on therapeutic effects, see section 5.1. 
 
4.2 Posology and method of administration 
 
Treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and 
treatment of conditions for which Cimzia is indicated. Patients should be given the special reminder 
card. 
 
Posology 
 
Rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, plaque psoriasis 
 
Loading dose  
The recommended starting dose of Cimzia for adult patients is 400 mg (given 
as 2 subcutaneous injections of 200 mg each) at weeks 0, 2 and 4. For rheumatoid arthritis and 
psoriatic arthritis, MTX should be continued during treatment with Cimzia where appropriate. 
 
Maintenance dose 
Rheumatoid arthritis 
After the starting dose, the recommended maintenance dose of Cimzia for adult patients with 
rheumatoid arthritis is 200 mg every 2 weeks. Once clinical response is confirmed, an alternative 
maintenance dosing of 400 mg every 4 weeks can be considered. MTX should be continued during 
treatment with Cimzia where appropriate. 
 
Axial spondyloarthritis 
After the starting dose, the recommended maintenance dose of Cimzia for adult patients with axial 
spondyloarthritis is 200 mg every 2 weeks or 400 mg every 4 weeks. After at least 1 year of treatment 
with Cimzia, in patients with sustained remission, a reduced maintenance dose of 200 mg every 4 
weeks may be considered (see section 5.1). 
 
Psoriatic arthritis 
After the starting dose, the recommended maintenance dose of Cimzia for adult patients with psoriatic 
arthritis is 200 mg every 2 weeks. Once clinical response is confirmed, an alternative maintenance 
dosing of 400 mg every 4 weeks can be considered. MTX should be continued during treatment with 
Cimzia where appropriate. 
 
For the above indications, available data suggest that clinical response is usually achieved 
within 12 weeks of treatment. Continued therapy should be carefully reconsidered in patients who 
show no evidence of therapeutic benefit within the first 12 weeks of treatment. 
 
Plaque psoriasis 
After the starting dose, the maintenance dose of Cimzia for adult patients with plaque psoriasis 
is 200 mg every 2 weeks. A dose of 400 mg every 2 weeks can be considered in patients with 
insufficient response (see section 5.1).  
Available data in adults with plaque psoriasis suggest that a clinical response is usually achieved 
within 16 weeks of treatment. Continued therapy should be carefully reconsidered in patients who 
show no evidence of therapeutic benefit within the first 16 weeks of treatment. Some patients with an 
initial partial response may subsequently improve with continued treatment beyond 16 weeks. 
 



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Missed dose 
Patients who miss a dose should be advised to inject the next dose of Cimzia as soon as they 
remember and then continue injecting subsequent doses as instructed. 
 
Special populations 
Paediatric population (< 18 years old) 
The safety and efficacy of Cimzia in children and adolescents below age 18 years have not yet been 
established. No data are available. 
 
Elderly patients (≥ 65 years old) 
No dose adjustment is required. Population pharmacokinetic analyses showed no effect of age (see 
section 5.2). 
 
Renal and hepatic impairment 
Cimzia has not been studied in these patient populations. No dose recommendations can be made (see 
section 5.2). 
 
Method of administration 
The total content (1 ml) of the pre-filled syringe should be administered as a subcutaneous injection 
only. Suitable sites for injection would include the thigh or abdomen. 
 
After proper training in injection technique, patients may self-inject using the pre-filled syringe if their 
physician determines that it is appropriate and with medical follow-up as necessary. The pre-filled 
syringe with needle guard should only be used by healthcare professionals. The physician should 
discuss with the patient which injection presentation option is the most appropriate. 
 
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 or opportunistic infections (see 
section 4.4). 
 
Moderate to severe heart failure (NYHA classes 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 must be monitored closely for signs and symptoms of infections including tuberculosis before, 
during and after treatment with Cimzia. Because the elimination of certolizumab pegol may take up 
to 5 months, monitoring should be continued throughout this period (see section 4.3). 
 
Treatment with Cimzia must not be initiated in patients with a clinically important active infection, 
including chronic or localised infections, until the infection is controlled (see section 4.3).  
 
Patients who develop a new infection while undergoing treatment with Cimzia should be monitored 
closely. Administration of Cimzia should be discontinued if a patient develops a new serious infection 
until the infection is controlled. Physicians should exercise caution when considering the use of 
Cimzia in patients with a history of recurring or opportunistic infection or with underlying conditions 
which may predispose patients to infections, including the use of concomitant immunosuppressive 
medications. 
 



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Patients with rheumatoid arthritis may not manifest typical symptoms of infection, including fever, 
due to their disease and concomitant medicinal products. Therefore, early detection of any infection, 
particularly atypical clinical presentations of a serious infection, is critical to minimise delays in 
diagnosis and initiation of treatment. 
 
Serious infections, including sepsis and tuberculosis (including miliary, disseminated and 
extrapulmonary disease), and opportunistic infections (e.g. histoplasmosis, nocardia, candidiasis) have 
been reported in patients receiving Cimzia. Some of these events have been fatal. 
 
Tuberculosis 
Before initiation of therapy with Cimzia, all patients must be evaluated for both active or inactive 
(latent) tuberculosis infection. This evaluation should include a detailed medical history for patients 
with a personal history of tuberculosis, with possible previous exposure to others with active 
tuberculosis, and with previous and/or current use of immunosuppressive therapy. Appropriate 
screening tests, e.g. tuberculin skin test and chest X-ray, should be performed in all patients (local 
recommendations may apply). It is recommended that the conduct of these tests should be recorded in 
the patient's 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 prior to or during treatment, Cimzia therapy must not be initiated 
and must be discontinued (see section 4.3). 
 
If inactive (‘latent’) tuberculosis is suspected, a physician with expertise in the treatment of 
tuberculosis should be consulted. In all situations described below, the benefit/risk balance of Cimzia 
therapy should be very carefully considered. 
 
If latent tuberculosis is diagnosed, appropriate anti-tuberculosis therapy must be started before 
initiating treatment with Cimzia and in accordance with local recommendations.  
Use of anti-tuberculosis therapy should also be considered before the initiation of Cimzia in patients 
with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be 
confirmed, and in patients who have significant risk factors for tuberculosis despite a negative test for 
latent tuberculosis. Biological tests for tuberculosis screening should be considered before starting 
Cimzia treatment if there is any potential latent tuberculosis infection, regardless of BCG vaccination. 
 
Despite previous or concomitant prophylactic treatment for tuberculosis, cases of active tuberculosis 
have occurred in patients treated with TNF-antagonists including Cimzia. Some patients who have 
been successfully treated for active tuberculosis have redeveloped tuberculosis while being treated 
with Cimzia. 
 
Patients should be instructed to seek medical advice if signs/symptoms (e.g. persistent cough, 
wasting/weight loss, low grade fever, listlessness) suggestive of a tuberculosis infection occur during 
or after therapy with Cimzia. 
 
Hepatitis B virus (HBV) reactivation 
Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including certolizumab 
pegol, 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 Cimzia. For patients who 
test positive for HBV infection, consultation with a physician with expertise in the treatment of 
hepatitis B is recommended.  
 
Carriers of HBV who require treatment with Cimzia should be closely monitored for signs and 
symptoms of active HBV infection throughout therapy and for several months following termination 
of therapy. Adequate data of 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 



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who develop HBV reactivation, Cimzia should be stopped and effective anti-viral therapy with 
appropriate supportive treatment should be initiated. 
 
Malignancies and lymphoproliferative disorders 
The potential role of TNF-antagonist therapy in the development of malignancies is not known. 
Caution should be exercised when considering TNF-antagonist therapy for patients with a history of 
malignancy or when considering continuing treatment in patients who develop malignancy.  
 
With the current knowledge, a possible risk for the development of lymphomas, leukaemia or other 
malignancies in patients treated with a TNF-antagonist cannot be excluded. 
 
In clinical trials with Cimzia and other TNF-antagonists, more cases of lymphoma and other 
malignancies have been reported among patients receiving TNF-antagonists than in control patients 
receiving placebo (see section 4.8). 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. 
 
No trials have been conducted that include patients with a history of malignancy, or that continue 
treatment in patients who develop malignancy, while receiving Cimzia.  
 
Skin cancers 
Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-antagonists 
including certolizumab pegol (see section 4.8). Periodic skin examination is recommended, 
particularly for patients with risk factors for skin cancer. 
 
Paediatric malignancy 
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) 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. 
 
Post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL), have been reported in patients 
treated with TNF-antagonists. This rare type of T-cell lymphoma has a very aggressive disease course 
and is usually fatal. The majority of reported TNF-antagonist cases occurred in adolescent and young 
adult males with Crohn’s disease or ulcerative colitis. Almost all of these patients had received 
treatment with the immunosuppressants azathioprine and/or 6-mercaptopurine concomitantly with a 
TNF-antagonist at or prior to diagnosis. A risk for development of hepatosplenic T-cell lymphoma in 
patients treated with Cimzia cannot be excluded. 
 
Chronic obstructive pulmonary disease (COPD) 
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. 
 
Congestive heart failure 
Cimzia is contraindicated in moderate or severe heart failure (see section 4.3). 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 congestive heart failure have also been reported in 
rheumatoid arthritis patients receiving Cimzia. Cimzia should be used with caution in patients with 
mild heart failure (NYHA class I/II). Treatment with Cimzia must be discontinued in patients who 
develop new or worsening symptoms of congestive heart failure. 



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Haematological reactions 
Reports of pancytopaenia, including aplastic anaemia, have been rare with TNF-antagonists. Adverse 
reactions of the haematologic system, including medically significant cytopaenia (e.g. leukopaenia, 
pancytopaenia, thrombocytopaenia) have been reported with Cimzia (see section 4.8). All patients 
should be advised to seek immediate medical attention if they develop signs and symptoms suggestive 
of blood dyscrasias or infection (e.g., persistent fever, bruising, bleeding, pallor) while on Cimzia. 
Discontinuation of Cimzia therapy should be considered in patients with confirmed significant 
haematological abnormalities. 
 
Neurological events 
Use of TNF-antagonists has been associated with rare cases of new onset or exacerbation of clinical 
symptoms and/or radiographic evidence of demyelinating disease, including multiple sclerosis. In 
patients with pre-existing or recent onset of demyelinating disorders, the benefits and risks of 
TNF-antagonist treatment should be carefully considered before initiation of Cimzia therapy. Rare 
cases of neurological disorders, including seizure disorder, neuritis and peripheral neuropathy, have 
been reported in patients treated with Cimzia. 
 
Hypersensitivity 
Severe hypersensitivity reactions have been reported rarely following Cimzia administration. Some of 
these reactions occurred after the first administration of Cimzia. If severe reactions occur, 
administration of Cimzia should be discontinued immediately and appropriate therapy instituted.  
 
There are limited data on the use of Cimzia in patients who have experienced a severe hypersensitivity 
reaction towards another TNF-antagonist; in these patients caution is needed. 
 
Latex-sensitivity  
The needle shield inside the removable cap of the CIMZIA pre-filled syringe contains a derivative of 
natural rubber latex (see section 6.5). Contact with natural rubber latex may cause severe allergic 
reactions in individuals sensitive to latex. No antigenic latex protein has to date been detected in the 
removable needle cap of the Cimzia pre-filled syringe. Nevertheless, a potential risk of 
hypersensitivity reactions cannot be completely excluded in latex-sensitive individuals. 
 
Immunosuppression 
Since tumour necrosis factor (TNF) mediates inflammation and modulates cellular immune responses, 
the possibility exists for TNF-antagonists, including Cimzia, to cause immunosupression, affecting 
host defences against infections and malignancies. 
 
Autoimmunity 
Treatment with Cimzia may result in the formation of antinuclear antibodies (ANA) and, 
uncommonly, in the development of a lupus-like syndrome (see section 4.8). The impact of long-term 
treatment with Cimzia on the development of autoimmune diseases is unknown. If a patient develops 
symptoms suggestive of a lupus-like syndrome following treatment with Cimzia, treatment must be 
discontinued. Cimzia has not been studied specifically in a lupus population (see section 4.8). 
 
Vaccinations 
Patients treated with Cimzia may receive vaccinations, except for live vaccines. No data are available 
on the response to live vaccinations or the secondary transmission of infection by live vaccines in 
patients receiving Cimzia. Live vaccines should not be administered concurrently with Cimzia. 
 
In a placebo-controlled clinical trial in patients with rheumatoid arthritis, similar antibody response 
between Cimzia and placebo treatment were observed when the pneumococcal polysaccharide vaccine 
and influenza vaccine were administered concurrently with Cimzia. Patients receiving Cimzia and 
concomitant methotrexate had a lower humoral response compared with patients receiving Cimzia 
alone. The clinical significance of this is unknown.  
 



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Concomitant use with other biologics 
Severe infections and neutropaenia were reported in clinical trials with concurrent use of anakinra (an 
interleukin-1 antagonist) or abatacept (a CD28 modulator) and another TNF-antagonist, etanercept, 
with no added benefit compared to TNF-antagonist therapy alone. Because of the nature of the adverse 
events seen with the combination of another TNF-antagonist with either abatacept or anakinra therapy, 
similar toxicities may also result from the combination of anakinra or abatacept and other 
TNF-antagonists. Therefore the use of certolizumab pegol in combination with anakinra or abatacept 
is not recommended (see section 4.5). 
 
Surgery 
There is limited safety experience with surgical procedures in patients treated with Cimzia. The 14-day 
half-life of certolizumab pegol should be taken into consideration if a surgical procedure is planned. A 
patient who requires surgery while on Cimzia should be closely monitored for infections, and 
appropriate actions should be taken. 
 
Activated partial thromboplastin time (aPTT) assay 
Interference with certain coagulation assays has been detected in patients treated with Cimzia. Cimzia 
may cause erroneously elevated aPTT assay results in patients without coagulation abnormalities. This 
effect has been observed with the PTT-Lupus Anticoagulant (LA) test and Standard Target Activated 
Partial Thromboplastin time (STA-PTT) Automate tests from Diagnostica Stago, and the HemosIL 
APTT-SP liquid and HemosIL lyophilised silica tests from Instrumentation Laboratories. Other aPTT 
assays may be affected as well. There is no evidence that Cimzia therapy has an effect on coagulation 
in vivo. After patients receive Cimzia, careful attention should be given to interpretation of abnormal 
coagulation results. Interference with thrombin time (TT) and prothrombin time (PT) assays have not 
been observed. 
 
Elderly patients 
In the clinical trials, there was an apparently higher incidence of infections among subjects ≥ 65 years 
of age, compared to younger subjects, although experience is limited. Caution should be exercised 
when treating the elderly patients, and particular attention paid with respect to occurrence of 
infections. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Concomitant treatment with methotrexate, corticosteroids, nonsteroidal anti-inflammatory drugs 
(NSAIDs) and analgesics showed no effect on the pharmacokinetics of certolizumab pegol based on a 
population pharmacokinetics analysis. 
 
The combination of certolizumab pegol and anakinra or abatacept is not recommended (see 
section 4.4). 
 
Co-administration of Cimzia with methotrexate had no significant effect on the pharmacokinetics of 
methotrexate. In study-to-study comparison, the pharmacokinetics of certolizumab pegol appeared 
similar to those observed previously in healthy subjects. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential  
The use of adequate contraception should be considered for women of childbearing potential. For 
women planning pregnancy, continued contraception may be considered for 5 months after the last 
Cimzia dose due to its elimination rate (see section 5.2), but the need for treatment of the woman 
should also be taken into account (see below). 
 
Pregnancy 
Data from more than 500 prospectively collected pregnancies exposed to Cimzia with known 
pregnancy outcomes, including more than 400 pregnancies exposed during the first trimester, does not 
indicate a malformative effect of Cimzia. However, the available clinical experience is too limited to, 



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with a reasonable certainty, conclude that there is no increased risk associated with Cimzia 
administration during pregnancy. 
 
Animal studies using a rodent anti-rat TNFα did not reveal evidence of impaired fertility or harm to 
the foetus. However, these are insufficient with respect to human reproductive toxicity (see 
section 5.3). Due to its inhibition of TNFα, Cimzia administered during pregnancy could affect normal 
immune response in the newborn.  
 
Cimzia should only be used during pregnancy if clinically needed. 
 
Non-clinical studies suggest low or negligible level of placental transfer of a homologue Fab-fragment 
of certolizumab pegol (no Fc region) (see section 5.3).  
 
In a clinical study 16 women were treated with certolizumab pegol (200 mg every 2 weeks or 400 mg 
every 4 weeks) during pregnancy. Certolizumab pegol plasma concentrations measured in 14 infants at 
birth were Below the Limit of Quantification (BLQ) in 13 samples; one was 0.042 µg/ml with an 
infant/mother plasma ratio at birth of 0.09%. At Week 4 and Week 8, all infant concentrations were 
BLQ. The clinical significance of low levels certolizumab pegol for infants is unknown. It is 
recommended to wait a minimum of 5 months following the mother’s last Cimzia administration 
during pregnancy before administration of live or live-attenuated vaccines (e.g. BCG vaccine), unless 
the benefit of the vaccination clearly outweighs the theoretical risk of administration of live or live-
attenuated vaccines to the infants. 
 
Breastfeeding 
In a clinical study in 17 lactating women treated with Cimzia, minimal transfer of certolizumab pegol 
from plasma to breast milk was observed. The percentage of the maternal certolizumab pegol dose 
reaching an infant during a 24 hour period was estimated to 0.04% to 0.30 %. In addition, since 
certolizumab pegol is a protein that is degraded in the gastrointestinal tract after oral administration, 
the absolute bioavailability is expected to be very low in a breastfed infant. 
 
Consequently, Cimzia can be used during breastfeeding. 
 
Fertility 
Effects on sperm motility measures and a trend of reduced sperm count in male rodents have been 
observed with no apparent effect on fertility (see section 5.3).  
 
In a clinical trial to assess the effect of certolizumab pegol on semen quality parameters, 20 healthy 
male subjects were randomized to receive a single subcutaneous dose of 400 mg of certolizumab pegol 
or placebo. During the 14-week follow-up, no treatment effects of certolizumab pegol were seen on 
semen quality parameters compared to placebo. 
 
4.7 Effects on ability to drive and use machines 
 
Cimzia may have a minor influence on the ability to drive and use machines. Dizziness (including 
vertigo, vision disorder and fatigue) may occur following administration of Cimzia (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Rheumatoid arthritis 
Cimzia was studied in 4,049 patients with rheumatoid arthritis in controlled and open label trials for 
up to 92 months. 
 
In the placebo-controlled studies, patients receiving Cimzia had an approximately 4 times greater 
duration of exposure compared with the placebo group. This difference in exposure is primarily due to 



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patients on placebo being more likely to withdraw early. In addition, Studies RA-I and RA-II had a 
mandatory withdrawal for non-responders at Week 16, the majority of whom were on placebo. 
 
The proportion of patients who discontinued treatment due to adverse events during the controlled 
trials was 4.4% for patients treated with Cimzia and 2.7% for patients treated with placebo. 
 
The most common adverse reactions belonged to the system organ classes Infections and infestations, 
reported in 14.4% of patients on Cimzia and 8.0% of patients on placebo, General disorders and 
administration site conditions, reported in 8.8% of patients on Cimzia and 7.4% of patients on placebo, 
and Skin and subcutaneous tissue disorders, reported in 7.0% of patients on Cimzia and 2.4% of 
patients on placebo. 
 
Axial spondyloarthritis 
Cimzia was initially studied in 325 patients with active axial spondyloarthritis (including ankylosing 
spondylitis and non-radiopraphic axial spondyloarthritis) in the AS001 clinical study for up to 4 years, 
which includes a 24-week placebo-controlled phase followed by a 24-week dose-blind period and 
a 156-week open-label treatment period. Cimzia was subsequently studied in 317 patients with non-
radiographic axial spondyloarthritis in a placebo-controlled study for 52 weeks (AS0006). Cimzia was 
also studied in patients with axial spondyloarthritis (including ankylosing spondylitis and non-
radiographic axial spondyloarthritis) in a clinical study for up to 96 weeks, which included a 48-week 
open-label run-in phase (N=736) followed by a 48-week placebo-controlled phase (N=313) for 
patients in sustained remission (C-OPTIMISE). In all 3 studies, the safety profile for these patients 
was consistent with the safety profile in rheumatoid arthritis and previous experience with Cimzia. 
 
Psoriatic arthritis  
Cimzia was studied in 409 patients with psoriatic arthritis in the PsA001 clinical study for up 
to 4 years which includes a 24-week placebo-controlled phase followed by a 24-week dose-blind 
period and a 168-week open-label treatment period. The safety profile for psoriatic arthritis patients 
treated with Cimzia was consistent with the safety profile in rheumatoid arthritis and previous 
experience with Cimzia. 
 
Plaque psoriasis 
Cimzia was studied in 1112 patients with psoriasis in controlled and open-label studies for up to 3 
years. In the Phase III program, the initial and maintenance periods were followed by a 96-week open-
label treatment period (see section 5.1). The long-term safety profile of Cimzia 400 mg every 2 weeks 
and Cimzia 200 mg every 2 weeks was generally similar and consistent with previous experience with 
Cimzia. 
 
During controlled clinical trials through Week 16, the proportion of patients with serious adverse 
events was 3.5% for Cimzia and 3.7% for placebo.  
The proportion of patients who discontinued treatment due to adverse events in the controlled clinical 
studies was 1.5% for patients treated with Cimzia and 1.4% for patients treated with placebo.  
 
The most common adverse reactions reported through Week 16 belonged to the system organ classes 
Infections and infestations, reported in 6.1% of patients on Cimzia and 7% of patients on placebo, 
General disorders and administration site conditions, reported in 4.1% of patients on Cimzia and 2.3% 
of patients on placebo, and Skin and subcutaneous tissue disorders, reported in 3.5% of patients on 
Cimzia and 2.8% of patients on placebo. 
 
Tabulated list of adverse reactions 
 
Adverse reactions based primarily on experience from the placebo-controlled clinical trials and 
postmarketing cases at least possibly related to Cimzia are listed in Table 1 below, according to 
frequency and system organ class. Frequency categories are defined as follows: Very common 
(≥ 1/10); Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1000 to < 1/100); Rare 
(≥ 1/10,000 to < 1/1000); Very rare (< 1/10,000), not known (cannot be estimated from the available 



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data). Within each frequency grouping, undesirable effects are presented in order of decreasing 
seriousness. 
 
Table 1 Adverse reactions in clinical trials and postmarketing 

System Organ Class  Frequency Adverse reactions  
Infections and 
infestations 

Common bacterial infections (including abscess), viral infections 
(including herpes zoster, papillomavirus, influenza) 

Uncommon sepsis (including multi-organ failure, septic shock), 
tuberculosis (including miliary, disseminated and 
extrapulmonary disease), fungal infections (includes 
opportunistic)  

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

Uncommon blood and lymphatic system malignancies (including 
lymphoma and leukaemia), solid organ tumours, non-
melanoma skin cancers, pre-cancerous lesions (including 
oral leukoplakia, melanocytic nevus), benign tumours 
and cysts (including skin papilloma) 

Rare gastrointestinal tumours, melanoma  
Not known Merkel cell carcinoma*, Kaposi’s sarcoma 

Blood and the lymphatic 
system disorders 

Common eosinophilic disorders, leukopaenia (including 
neutropaenia, lymphopaenia) 

Uncommon anaemia, lymphadenopathy, thrombocytopaenia, 
thrombocytosis 

Rare pancytopaenia, splenomegaly, erythrocytosis, white 
blood cell morphology abnormal 

Immune system disorders Uncommon vasculitides, lupus erythematosus, drug hypersensitivity 
(including anaphylactic shock), allergic disorders, 
auto-antibody positive 

Rare angioneurotic oedema, sarcoidosis, serum sickness, 
panniculitis (including erythema nodosum), worsening of 
symptoms of dermatomyositis** 

Endocrine disorders Rare thyroid disorders 
Metabolism and nutrition 
disorders 

Uncommon electrolyte imbalance, dyslipidaemia, appetite disorders, 
weight change 

Rare haemosiderosis 
Psychiatric disorders Uncommon anxiety and mood disorders (including associated 

symptoms) 
Rare suicide attempt, delirium, mental impairment 

Nervous system disorders Common headaches (including migraine), sensory abnormalities 
Uncommon peripheral neuropathies, dizziness, tremor 
Rare seizure, cranial nerve inflammation, impaired 

coordination or balance 
Not known multiple sclerosis*, Guillain-Barré syndrome* 

Eye disorders Uncommon visual disorder (including decreased vision), eye and 
eyelid inflammation, lacrimation disorder 

Ear and labyrinth 
disorders 

Uncommon tinnitus, vertigo 

Cardiac disorders Uncommon cardiomyopathies (including heart failure), ischaemic 
coronary artery disorders, arrhythmias (including atrial 
fibrillation), palpitations 

Rare pericarditis, atrioventricular block 



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System Organ Class  Frequency Adverse reactions  
Vascular disorders Common hypertension 

Uncommon haemorrhage or bleeding (any site), hypercoagulation 
(including thrombophlebitis, pulmonary embolism), 
syncope, oedema (including peripheral, facial), 
ecchymoses (including haematoma, petechiae) 

Rare cerebrovascular accident, arteriosclerosis, Raynaud’s 
phenomenon, livedo reticularis, telangiectasia 

Respiratory, thoracic and 
mediastinal disorders 

Uncommon asthma and related symptoms, pleural effusion and 
symptoms, respiratory tract congestion and 
inflammation, cough 

Rare interstitial lung disease, pneumonitis 
Gastrointestinal disorders Common nausea 

Uncommon ascites, gastrointestinal ulceration and perforation, 
gastrointestinal tract inflammation (any site), stomatitis, 
dyspepsia, abdominal distension, oropharyngeal dryness 

Rare odynophagia, hypermotility 
Hepatobiliary disorders Common hepatitis (including hepatic enzyme increased) 

Uncommon hepatopathy (including cirrhosis), cholestasis, blood 
bilirubin increased 

Rare cholelithiasis 
Skin and subcutaneous 
tissue disorders 

Common rash 
Uncommon alopecia, new onset or worsening of psoriasis (including 

palmoplantar pustular psoriasis) and related conditions, 
dermatitis and eczema, sweat gland disorder, skin ulcer, 
photosensitivity, acne, skin discolouration, dry skin, nail 
and nail bed disorders 

Rare skin exfoliation and desquamation, bullous conditions, 
hair texture disorder, Stevens-Johnson syndrome**, 
erythema multiforme**, lichenoid reactions 

Musculoskeletal, 
connective tissue and 
bone disorders 

Uncommon muscle disorders, blood creatine phosphokinase 
increased 

Renal and urinary 
disorders 

Uncommon renal impairment, blood in urine, bladder and urethral 
symptoms  

Rare nephropathy (including nephritis) 
Reproductive system and 
breast disorders 

Uncommon menstrual cycle and uterine bleeding disorders (including 
amenorrhea), breast disorders  

Rare sexual dysfunction  
General disorders and 
administration site 
conditions 

Common pyrexia, pain (any site), asthaenia, pruritus (any site), 
injection site reactions 

Uncommon chills, influenza-like illness, altered temperature 
perception, night sweats, flushing 

Rare fistula (any site) 
Investigations Uncommon blood alkaline phosphatase increased, coagulation time 

prolonged 
Rare blood uric acid increased 

Injury, poisoning and 
procedural complications 

Uncommon skin injuries, impaired healing 

*These events have been related to the class of TNF-antagonists, but incidence with certolizumab 
pegol is not known. 
**These events have been related to the class of TNF-antagonists. 
 
The additional following adverse reactions have been observed uncommonly with Cimzia in other 
indications: gastrointestinal stenosis and obstructions, general physical health deterioration, abortion 
spontaneous and azoospermia. 



13 

 
Description of selected adverse reactions 
 
Infections 
The incidence rate of new cases of infections in placebo-controlled clinical trials in rheumatoid 
arthritis was 1.03 per patient-year for all Cimzia-treated patients and 0.92 per patient-year for placebo-
treated patients. The infections consisted primarily of upper respiratory tract infections, urinary tract 
infections, and lower respiratory tract infections and herpes viral infections (see sections 4.3 and 4.4). 
 
In the placebo-controlled clinical trials in rheumatoid arthritis, there were more new cases of serious 
infection in the Cimzia treatment groups (0.07 per patient-year; all doses), compared with placebo 
(0.02 per patient-year). The most frequent serious infections included pneumonia, tuberculosis 
infections. Serious infections also included invasive opportunistic infections (e.g. pneumocystosis, 
fungal oesophagitis, nocardiosis and herpes zoster disseminated). There is no evidence of an increased 
risk of infections with continued exposure over time (see section 4.4). 
 
The incidence rate of new cases of infections in placebo-controlled clinical trials in psoriasis 
was 1.37 per patient-year for all Cimzia-treated patients and 1.59 per patient-year for placebo-treated 
patients. The infections consisted primarily of upper respiratory tract infections and viral infections 
(including herpes infections). The incidence of serious infections was 0.02 per patient-year in Cimzia 
treated patients. No serious infections were reported in the placebo-treated patients. There is no 
evidence of an increased risk of infections with continued exposure over time. 
 
Malignancies and lymphoproliferative disorders 
Excluding non-melanoma of the skin, 121 malignancies including 5 cases of lymphoma were observed 
in the Cimzia RA clinical trials in which a total of 4,049 patients were treated, 
representing 9,277 patient-years. Cases of lymphoma occurred at an incidence rate 
of 0.05 per 100 patient-years and melanoma at an incidence rate of 0.08 per 100 patient-years with 
Cimzia in rheumatoid arthritis clinical trials (see section 4.4). One case of lymphoma was also 
observed in the Phase III psoriatic arthritis clinical trial. 
 
Excluding non-melanoma skin cancer, 11 malignancies including 1 case of lymphoma were observed 
in the Cimzia psoriasis clinical trials in which a total of 1112 patients were treated, representing 2300 
patient-years. 
 
Autoimmunity 
In the rheumatoid arthritis pivotal studies, for subjects who were ANA negative at baseline, 16.7% of 
those treated with Cimzia developed positive ANA titers, compared with 12.0% of subjects in the 
placebo group. For subjects who were anti-dsDNA antibody negative at baseline, 2.2% of those treated 
with Cimzia developed positive anti-dsDNA antibody titers, compared with 1.0% of subjects in the 
placebo group. In both placebo-controlled and open-label follow-up clinical trials for rheumatoid 
arthritis, cases of lupus-like syndrome were reported uncommonly. There have been rare reports of 
other immune-mediated conditions; the causal relationship to Cimzia is not known. The impact of 
long-term treatment with Cimzia on the development of autoimmune diseases is unknown. 
 
Injection site reactions 
In the placebo-controlled rheumatoid arthritis clinical trials, 5.8% of patients treated with Cimzia 
developed injection site reactions such as erythema, itching, haematoma, pain, swelling or bruising, 
compared to 4.8% of patients receiving placebo. Injection site pain was observed in 1.5% of patients 
treated with Cimzia with no cases leading to withdrawal. 
 
Creatine phosphokinase elevations 
The frequency of creatine phosphokinase (CPK) elevations was generally higher in patients with 
axSpA as compared to the RA population. The frequency was increased both in patients treated with 
placebo (2.8% vs 0.4% in axSpA and RA populations, respectively) as well as in patients treated with 
Cimzia (4.7% vs 0.8% in axSpA and RA populations, respectively). The CPK elevations in the axSpA 



14 

study were mostly mild to moderate, transient in nature and of unknown clinical significance with no 
cases leading to withdrawal. 
 
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. Multiple doses of up to 800 mg 
subcutaneously and 20 mg/kg intravenously have been administered. In cases of overdose, it is 
recommended that patients are monitored closely for any adverse reactions or effect, and appropriate 
symptomatic treatment initiated immediately. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: immunosuppressants, tumour necrosis factor alpha (TNFα) inhibitors, 
ATC code: L04AB05 
 
Mechanism of action 
 
Cimzia has a high affinity for human TNFα and binds with a dissociation constant (KD) of 90 pM. 
TNFα is a key pro-inflammatory cytokine with a central role in inflammatory processes. Cimzia 
selectively neutralises TNFα (IC90 of 4 ng/ml for inhibition of human TNFα in the in vitro 
L929 murine fibrosarcoma cytotoxicity assay) but does not neutralise lymphotoxin α (TNFβ).  
 
Cimzia was shown to neutralise membrane associated and soluble human TNFα in a dose-dependent 
manner. Incubation of monocytes with Cimzia resulted in a dose-dependent inhibition of 
lipopolysaccharide (LPS)-induced TNFα and IL1β production in human monocytes. 
 
Cimzia does not contain a fragment crystallisable (Fc) region, which is normally present in a complete 
antibody, and therefore does not fix complement or cause antibody-dependent cell-mediated 
cytotoxicity in vitro. It does not induce apoptosis in vitro in human peripheral blood-derived 
monocytes or lymphocytes, or neutrophil degranulation. 
 
Clinical efficacy 
 
Rheumatoid arthritis 
The efficacy and safety of Cimzia have been assessed in 2 randomised, placebo-controlled, double-
blind clinical trials in patients ≥ 18 years of age with active rheumatoid arthritis diagnosed according 
to American College of Rheumatology (ACR) criteria, RA-I (RAPID 1) and RA-II (RAPID 2). 
Patients had ≥ 9 swollen and tender joints each and had active RA for at least 6 months prior to 
baseline. Cimzia was administered subcutaneously in combination with oral MTX for a minimum 
of 6 months with stable doses of at least 10 mg weekly for 2 months in both trials. There is no 
experience with Cimzia in combination with DMARDs other than MTX. 
 
The efficacy and safety of Cimzia was assessed in DMARD-naïve adult patients with active RA in a 
randomized, placebo-controlled, double-blind clinical trial (C-EARLY). In the C-EARLY trial patients 
were ≥ 18 years of age and had ≥ 4 swollen and tender joints each and must have been diagnosed with 
moderate to severe active and progressive RA within 1 year (as defined by the 2010 ACR/European 
League Against Rheumatism (EULAR) classification criteria). Patients had a mean time since 
diagnosis at baseline of 2.9 months and were DMARD naïve (including MTX). For both the Cimzia 



15 

and placebo arms, MTX was initiated as of Week 0 (10 mg/week), titrated up to maximum tolerated 
dose by Week 8 (min 15 mg/week, max 25 mg/week allowed), and maintained throughout the study 
(average dose of MTX after Week 8 for placebo and Cimzia was 22.3 mg/week and 21.1 mg/week 
respectively). 
 
Table 2 Clinical trial description 

Study 
number 

Patient 
numbers 

Active dose regimen Study objectives 
 

RA-I 
(52 weeks) 

982 400 mg (0,2,4 weeks) 
with MTX 

200 mg or 400 mg 
every 2 weeks with MTX 

Evaluation for treatment of signs and 
symptoms and inhibition of structural damage.  
Co-primary endpoints: ACR 20 at Week 24 and 

change from baseline in mTSS at Week 52 
RA-II 

(24 weeks) 
619 400 mg (0,2,4 weeks) 

with MTX 
200 mg or 400 mg 
every 2 weeks with 

MTX 

Evaluation for treatment of signs and 
symptoms and inhibition of structural damage. 

Primary endpoint: ACR 20 at Week 24.  

C-EARLY 
(to 52 wee

ks) 

879 400 mg (0,2,4 weeks) 
with MTX 

200 mg every 2 weeks 
with MTX 

Evaluation for treatment of signs and 
symptoms and inhibition of structural damage 

in DMARD naïve patients.  
Primary endpoint: proportion of subjects in 

sustained remission* at Week 52 
mTSS: modified Total Sharp Score 
*Sustained remission at Week 52 is defined as DAS28[ESR] <2.6 at both Week 40 and Week 52. 
 
Signs and symptoms 
The results of clinical trials RA-I and RA-II are shown in Table 3. Statistically significantly greater 
ACR 20 and ACR 50 responses were achieved from Week 1 and Week 2, respectively, in both clinical 
trials compared to placebo. Responses were maintained through Weeks 52 (RA-I) and 24 (RA-II). Of 
the 783 patients initially randomised to active treatment in RA-I, 508 completed 52 weeks of placebo-
controlled treatment and entered the open-label extension study. Of these, 427 completed 2 years of 
open-label follow-up and thus had a total exposure to Cimzia of 148 weeks overall. The observed 
ACR 20 response rate at this timepoint was 91%.The reduction (RA-I) from Baseline in DAS28 (ESR) 
also was significantly greater (p<0.001) at Week 52 (RA-I) and Week 24 (RA-II) compared to placebo 
and maintained through 2 years in the open-label extension trial to RA-I. 
 
Table 3 ACR response in clinical trials RA-I and RA-II 

 Study RA-I 
Methotrexate combination 

(24 and 52 weeks) 

Study RA-II 
Methotrexate combination 

(24 weeks) 
Response Placebo + MTX 

 
N=199 

Cimzia  
200 mg + MTX 
every 2 weeks 

 
N=393 

Placebo + MTX 
 

N=127 

Cimzia  
200 mg + MTX 
every 2 weeks 

 
N=246 

ACR 20     
Week 24 14% 59%** 9% 57%** 
Week 52 13% 53%** N/A N/A 
ACR 50     
Week 24 8% 37%** 3% 33%** 
Week 52 8% 38%** N/A N/A 



16 

ACR 70     
Week 24 3% 21%** 1% 16%* 
Week 52 4% 21%** N/A N/A 
Major 
Clinical 
Responsea. 

1% 13%**   

Cimzia vs. placebo: *p≤0.01, ** p<0.001 
a. Major clinical response is defined as achieving ACR 70 response at every assessment over a 
continuous 6-month period 
Wald p-values are quoted for the comparison of treatments using logistic regression with factors for 
treatment and region. 
Percentage response based upon number of subjects contributing data (n) to that endpoint and time 
point which may differ from N 

 
The C-EARLY trial met its primary and key secondary endpoints. The key results from the study are 
presented in table 4.  
 
Table 4: C-EARLY trial: percent of patients in sustained remission and sustained low disease 

activity at Week 52 
Response Placebo+MTX 

N= 213 
Cimzia 200 mg + MTX 

N= 655 
Sustained remission* 
(DAS28(ESR) <2.6 at both Week 40 and Week 52) 

15.0 % 28.9%** 

Sustained low disease activity 
(DAS28(ESR) ≤3.2 at both Week 40 and Week 52) 

28.6 % 43.8%** 

*Primary endpoint of C-EARLY trial (to Week 52) 
Full analysis set, non-responder imputation for missing values. 
**Cimzia+MTX vs placebo+MTX: p<0.001 
p value was estimated from a logistic regression model with factors for treatment, region, and time 
since RA diagnosis at Baseline (≤4 months vs >4 months) 

 
Patients in the Cimzia+MTX group had a greater reduction from baseline in DAS 28 (ESR) compared 
with the placebo+MTX group observed as early as Week 2 and continued through 
Week 52 (p<0.001 at each visit). Assessments on remission (DAS28(ESR) <2.6), Low Disease 
Activity (DAS28(ESR) ≤3.2) status, ACR50 and ACR 70 by visit demonstrated that Cimzia+MTX 
treatment led to faster and greater responses than PBO+MTX treatment. These results were maintained 
over 52 weeks of treatment in DMARD-naïve subjects.  
 
Radiographic response 
In RA-I, structural joint damage was assessed radiographically and expressed as change in mTSS and 
its components, the erosion score and joint space narrowing (JSN) score, at Week 52, compared to 
baseline. Cimzia patients demonstrated significantly less radiographic progression than patients 
receiving placebo at Week 24 and Week 52 (see Table 5). In the placebo group, 52% of patients 
experienced no radiographic progression (mTSS ≤ 0.0) at Week 52 compared to 69% in the 
Cimzia 200 mg treatment group. 
 



17 

Table 5 Changes over 12 months in RA-I 
 Placebo + MTX 

N=199 
Mean (SD) 

Cimzia 200 mg + MTX 
N=393 

Mean (SD) 

Cimzia 200 mg + MTX – 
Placebo + MTX 
Mean Difference 

mTSS    
Week 52 2.8 (7.8) 0.4 (5.7) -2.4 
Erosion Score    
Week 52 1.5 (4.3) 0.1 (2.5) -1.4 
JSN Score    
Week 52 1.4 (5.0) 0.4 (4.2) -1.0 
p-values were < 0.001 for both mTSS and erosion score and ≤ 0.01 for JSN score. An ANCOVA 
was fitted to the ranked change from baseline for each measure with region and treatment as factors 
and rank baseline as a covariate. 

 
Of the 783 patients initially randomised to active treatment in RA-I, 508 completed 52 weeks of 
placebo-controlled treatment and entered the open-label extension study. Sustained inhibition of 
progression of structural damage was demonstrated in a subset of 449 of these patients who completed 
at least 2 years of treatment with Cimzia (RA-I and open-label extension study) and had evaluable data 
at the 2-year timepoint. 
 
In C-EARLY, Cimzia+ MTX inhibited the radiographic progression compared to placebo+MTX at 
Week 52 (see Table 6). In the placebo+MTX group, 49.7% of patients experienced no radiographic 
progression (change in mTSS ≤0.5) at Week 52 compared to 70.3% in the Cimzia+MTX group 
(p<0.001). 
 
Table 6 Radiographic change at Week 52 in trial C-EARLY 

 Placebo +MTX 
N= 163 

Mean (SD) 

Cimzia 200 mg + MTX 
N = 528 

Mean (SD) 

Cimzia 200 mg + MTX – 
Placebo +MTX 

Difference* 
mTSS 
Week 52 

1.8 (4.3) 0.2 (3.2)** -0.978 (-1.005, -0.500) 

Erosion score 
Week 52 

1.1 (3.0) 0.1 (2.1)** -0.500 (-0.508, -0.366) 

JSN score 
Week 52 

0.7 (2.3) 0.1 (1.7)** 0.000 (0.000, 0.000) 

Radiographic set with linear extrapolation. 
* Hodges-Lehmann point estimate of shift and 95% asymptotic (Moses) confidence interval. 
**Cimzia+MTX vs placebo+MTX p<0.001. p value was estimated from an ANCOVA model on the 
ranks with treatment, region, time since RA diagnosis at Baseline (≤4 months vs >4 months) as 
factors and Baseline rank as a covariate. 

 
Physical function response and health-related outcomes 
In RA-I and RA-II, Cimzia-treated patients reported significant improvements in physical function as 
assessed by the Health Assessment Questionnaire – Disability Index (HAQ-DI) and in tiredness 
(fatigue) as reported by the Fatigue Assessment Scale (FAS) from Week 1 through to the end of the 
studies compared to placebo. In both clinical trials, Cimzia-treated patients reported significantly 
greater improvements in the SF-36 Physical and Mental Component Summaries and all domain scores. 
Improvements in physical function and HRQoL were maintained through 2 years in the open-label 
extension to RA-I. Cimzia-treated patients reported statistically significant improvements in the Work 
Productivity Survey compared to placebo. 
 
In C-EARLY, Cimzia+MTX-treated patients reported significant improvements at Week 52 compared 
to placebo+MTX in pain as assessed by the Patient Assessment of Arthritis Pain (PAAP) – 48,5 vs 
- 44,0 (least square mean) (p<0.05). 
 



18 

DoseFlex clinical trial 
The efficacy and safety of 2 dose regimens (200 mg every 2 weeks and 400 mg every 4 weeks) of 
Cimzia versus placebo were assessed in an 18-week, open-label, run-in, and 16-week randomised, 
double-blind, placebo-controlled clinical trial in adult patients with active rheumatoid arthritis 
diagnosed according to the ACR criteria who had inadequate response to MTX. 
 
Patients received loading doses of Cimzia 400 mg at weeks 0, 2, and 4 followed by Cimzia 200 mg 
every 2 weeks during the initial open label period. Responders (achieved ACR 20) at week 16 were 
randomised at week 18 to Cimzia 200 mg every 2 weeks, Cimzia 400 mg every 4 weeks, or placebo in 
combination with MTX for an additional 16 weeks (total trial length: 34 weeks). These 3 groups were 
well balanced with regards to clinical response following the active run-in period (ACR 20: 83-84% at 
week 18). 
 
The primary endpoint of the study was the ACR 20 responder rate at week 34. The results at 
week 34 are shown in Table 7. Both Cimzia regimens showed sustained clinical response and were 
statistically significant compared to placebo at week 34. The ACR 20 endpoint was achieved for both 
Cimzia 200 mg every 2 weeks and 400 mg every 4 weeks. 
 
Table 7 ACR response in DoseFlex clinical trial at week 34 

Treatment regimen week 0 to 16 Cimzia 400 mg + MTX at week 0, 2 and 4, followed by 
Cimzia 200 mg + MTX every 2 weeks  

Randomised, double-blind 
treatment regimen 
week 18 to 34 
 

Placebo + MTX 
 
 

N=69 

Cimzia  
200 mg + MTX 
every 2 weeks 

N=70 

Cimzia  
400 mg + MTX 
every 4 weeks 

N=69 
ACR 20 
p-value* 

45% 
N/A 

67% 
0.009 

65% 
0.017 

ACR 50 
p-value* 

30% 
N/A 

50% 
0.020 

52% 
0.010 

ACR 70 
p-value* 

16% 
N/A 

30% 
0.052 

38% 
0.005 

N/A: Not Applicable 
*Wald p-values for Cimzia 200 mg vs. placebo and Cimzia 400 mg vs. placebo comparisons are 
estimated from a logistic regression model with factors for treatment 

 
Axial spondyloarthritis (non-radiographic axial spondyloarthritis and ankylosing spondylitis 
subpopulations) 
AS001 
The efficacy and safety of Cimzia were assessed in one multicenter, randomized, double-blind, 
placebo-controlled trial (AS001) in 325 patients ≥18 years of age with adult-onset active axial 
spondyloarthritis for at least 3 months as defined by the Assessment of Spondyloarthritis International 
Society (ASAS) Classification Criteria for axial spondyloarthritis. The axial spondyloarthritis overall 
population included subpopulations with and without (non-radiographic axial spondyloarthritis [nr-
axSpA]) radiographic evidence for ankylosing spondylitis (AS) (also known as radiographic axial 
spondyloarthritis). Patients had active disease as defined by the Bath Ankylosing Spondylitis Disease 
Activity Index (BASDAI) ≥ 4, spinal pain ≥ 4 on a 0 to 10 Numerical Rating Scale (NRS) and 
increased CRP or current evidence of sacroiliitis on Magnetic Resonance Imaging (MRI). Patients 
must have been intolerant to or had an inadequate response to at least one NSAID. Overall, 16% of 
patients had prior TNF-antagonist exposure. Patients were treated with a loading dose of 
Cimzia 400 mg at Weeks 0, 2 and 4 (for both treatment arms) or placebo followed by either 200 mg of 
Cimzia every 2 weeks or 400 mg of Cimzia every 4 weeks or placebo. 87.7% of patients received 
concomitant NSAIDs. The primary efficacy endpoint was the ASAS20 response rate at Week 12. 
The 24-week double-blind, placebo-controlled treatment period of the study was followed by a 24-
week dose-blind treatment period, and a 156-week open-label treatment period. The maximum 
duration of the study was 204 weeks. All patients received Cimzia in both the dose-blind and open-



19 

label follow-up periods. A total of 199 subjects (61.2% of randomized subjects) completed the study 
through Week 204.  
 
Key efficacy outcomes 
In AS001 clinical trial, at Week 12 ASAS20 responses were achieved by 58% of patients receiving 
Cimzia 200 mg every 2 weeks and 64% of patients receiving Cimzia 400 mg every 4 weeks as 
compared to 38% of patients receiving placebo (p<0.01). In the overall population, the percentage of 
ASAS20 responders was clinically relevant and significantly higher for the Cimzia 200 mg 
every 2 weeks and Cimzia 400 mg every 4 weeks treatment groups compared to placebo group at 
every visit from Week 1 through Week 24 (p≤0.001 at each visit). At Weeks 12 and 24, the percentage 
of subjects with an ASAS40 response was greater in the Cimzia-treated groups compared to placebo.  
 
Similar results were achieved in both the ankylosing spondylitis and non-radiographic axial 
spondyloarthritis subpopulations. In women, ASAS20 responses were not statistically significantly 
different from placebo until after the Week 12 time point. 
 
Improvements in ASAS5/6, Partial Remission and BASDAI-50 were statistically signficant at 
Week 12 and Week 24 and were sustained up to Week 48 in the overall popualtion as well as in the 
subpopulations. Key efficacy outcomes from the AS001 clinical trial are shown in Table -8. Among 
patients remaining in the study, improvements in all afore-mentioned key efficacy outcomes were 
maintained through Week 204 in the overall population as well as in the subpopulations. 
 
Table 8 Key efficacy outcomes in AS001 clinical trial (percent of patients) 

 
 

Parameters 

Ankylosing spondylitis Non-radiographic 
axial 

spondyloarthritits 

 Axial 
spondyloarthritis 

Overall Population 
 Placebo 

N=57 
Cimzia 

all dosing 
regimens(a) 

N=121 

Placebo 
N=50 

Cimzia all 
dosing 

regimens(a) 
N=97 

Placebo 
N=107 

 

Cimzia all 
dosing 

regimens(a) 
N=218 

ASAS20(b,c) 
Week 12 
Week 24 

 
37% 
33% 

 
60%* 

69%** 

 
40% 
24% 

 
61%* 

68%** 

 
38% 
29% 

 
61%** 
68%** 

ASAS40(c,d) 
Week 12 
Week 24 

 
19% 
16% 

 
45%** 
53%** 

 
16% 
14% 

 
47%** 
51%** 

 
18% 
15% 

 
46%** 
52%** 

ASAS 5/6(c,d) 
Week 12 
Week 24 

 
9% 
5% 

 
42%** 
40%** 

 
8% 
4% 

 
44%** 
45%** 

 
8% 
5% 

 
43%** 
42%** 

Partial remission(c,d) 
Week 12 
Week 24 

 
2% 
7% 

 
20%** 
28%** 

 
6% 
10% 

 
29%** 
33%** 

 
4% 
9% 

 
24%** 
30%** 

BASDAI 50(c,d) 
Week 12 
Week 24 

 
11% 
16% 

 
41%** 
49%** 

 
16% 
20% 

 
49%** 
57%** 

 
13% 
18% 

 
45%** 
52%** 

(a) Cimzia all dosing regimen = data from Cimzia 200 mg administered every 2 weeks preceded by a 
loading dose of 400 mg at Weeks 0, 2 and 4 plus Cimzia 400 mg administered every 4 weeks preceded 
by a loading dose of 400 mg at Weeks 0, 2 and 4 
(b) Results are from the randomized set 
(c) Wald p-values are quoted for the comparison of treatments using logistic regression with factors for 
treatment and region.  
(d) Full Analysis Set  
NA = not available 
*p≤0.05, Cimzia vs placebo 
**p<0.001, Cimzia vs placebo 

 



20 

Spinal mobility 
Spinal mobility was assessed in the double-blind, placebo-controlled period by using BASMI at 
several time points including Baseline, Week 12 and Week 24. Clinically meaningful and statistically 
significant differences in Cimzia-treated patients compared with placebo-treated patients were 
demonstrated at each post-baseline visit. The difference from placebo tended to be greater in nr-axSpA 
than in the AS subpopulation which may be due to less chronic structural damage in nr-axSpA 
patients. 
The improvement in BASMI linear score achieved at Week 24 was maintained through Week 204 for 
patients who remained in the study. 
 
Physical function response and health-related outcomes  
In the AS001 clinical trial, Cimzia-treated patients reported significant improvements in physical 
function as assessed by the BASFI and in pain as assessed by the Total and Nocturnal Back Pain NRS 
scales as compared to placebo. Cimzia-treated patients reported significant improvements in tiredness 
(fatigue) as reported by the BASDAI-fatigue item and in health-related quality of life as measured by 
the ankylosing spondylitis QoL (ASQoL) and the SF-36 Physical and Mental Component Summaries 
and all domain scores as compared to placebo. Cimzia-treated patients reported significant 
improvements in axial spondyloarthritis-related productivity at work and within household, as reported 
by the Work Productivity Survey as compared to placebo. For patients remaining in the study, 
improvements in all afore-mentioned outcomes were largely maintained through Week 204. 
 
Inhibition of inflammation in Magnetic Resonance Imaging (MRI) 
In an imaging sub-study including 153 patients, signs of inflammation were assessed by MRI at 
week 12 and expressed as change from baseline in SPARCC (Spondyloarthritis Research Consortium 
of Canada) score for sacroiliac joints and ASspiMRI-a score in the Berlin modifications for the spine. 
At week 12, significant inhibition of inflammatory signs in both sacroiliac joints and the spine was 
observed in the Cimzia-treated patients (all dose group), in the overall axial spondyloarthritis 
population as well as in the sub-populations of ankylosing spondylitis and non-radiographic axial 
spondyloarthritis. 
Among patients remaining in the study, who had both baseline values and week 204 values, inhibition 
of inflammatory signs in both the sacroiliac joints (n=72) and spine (n=82) was largely maintained 
through Week 204 in the overall axial spondyloarthritis population as well as in both the AS and the 
nr-axSpA subpopulations. 
 

C-OPTIMISE 

The efficacy and safety of dose reduction and treatment withdrawal in patients in sustained remission 
were assessed in adult patients (18-45 years of age) with early active axSpA (symptom duration of less 
than 5 years), an ASDAS score ≥2.1 (and similar disease inclusion criteria as in the AS001 study), and 
who had inadequate response to at least 2 NSAIDs or an intolerance to or contraindication for 
NSAIDs. Patients included both the AS and nr-axSpA subpopulations of axSpA, and were enrolled 
into an open-label run-in 48-Week period (Part A) during which they all received 3 loading doses of 
Cimzia 400 mg at Weeks 0, 2, and 4 followed by Cimzia 200 mg every 2 weeks from Week 6 to Week 
46.   

Patients who achieved sustained remission (defined as having inactive disease [ASDAS<1.3] over a 
period of at least 12 weeks) and remained in remission at week 48, were randomized into Part B and 
received either Cimzia 200 mg every 2 weeks (N=104), Cimzia 200 mg every 4 weeks (dose 
reduction, N=105), or placebo (treatment withdrawal, N=104) for 48 Weeks.  

The primary efficacy variable was the percentage of patients who did not experience a flare during 
Part B. 

Patients who experienced a flare in Part B, ie, had an ASDAS ≥2.1 at 2 consecutive visits or 
ASDAS >3.5 at any visit during Part B, received escape treatment of Cimzia 200 mg every 2 weeks 
for at least 12 weeks (with a loading dose of Cimzia 400 mg at Week 0, 2 and 4 in placebo-treated 
patients).  



21 

Clinical response 

The percentage of patients who achieved sustained remission at Week 48 in Part A was 43.9% for the 
overall axSpA population, and was similar in the nr-axSpA (45.3%) and AS (42.8%) subpopulations. 

Among the patients who were randomized in Part B (N=313), a statistically significant (p <0.001, 
NRI) greater proportion of patients did not experience a flare when continuing treatment with 
Cimzia 200 mg every 2 weeks (83.7%) or Cimzia 200 mg every 4 weeks (79.0%) compared with 
treatment withdrawal (20.2%).   

The difference in time to flare between the treatment withdrawal group and either of the Cimzia 
treatment groups, was statistically significant (p<0.001 for each comparison) and clinically 
meaningful. In the placebo group, flares started approximately 8 weeks after Cimzia was withdrawn, 
with the majority of flares occurring within 24 weeks of treatment withdrawal (Figure 1).  

Figure 1  Kaplan-Meier curve of time to flare 

 
Non responder imputation (NRI) was used; Results are for the Randomized Set 
Note: Time to flare was defined as the time from the date of randomization to the date of the flare. For study participants who did not have a  
flare, the time to flare was censored at the date of Week 96 Visit. 
The Kaplan-Meier plot was truncated to 97 weeks when <5% of participants were still remaining in the study. 
 

Results for Part B are presented in Table 9. 

 



22 

Table 9  Maintenance of clinical response in Part B at Week 96  

Endpoints 

Placebo 
(treatment 

withdrawal) 
N=104 

CIMZIA 200 mg 
every 2 weeks 

N=104 

CIMZIA 200 mg  

every 4 weeks 
N=105 

ASDAS-MI, n (%)1  
Part B Baseline (Week 48) 84 (80.8) 90 (86.5) 89 (84.8) 

Week 96 11 (10.6) 70 (67.3)* 61 (58.1)* 

ASAS40, n (%)1  

Part B Baseline (Week 48) 101 (97.1) 103 (99.0) 101 (96.2) 

Week 96 22 (21.2) 88 (84.6)* 77 (73.3)* 

BASDAI change from Part B 
baseline (Week 48), LS mean (SE)2  

Week 96 3.02 (0.226) 0.56 (0.176)* 0.78 (0.176)* 

ASDAS change from Part B 
baseline (Week 48), LS mean (SE)2  

Week 96 1.66 (0.110) 0.24 (0.077)* 0.45 (0.077)* 
1 Non responder imputation (NRI) was used; Results are for the Randomized Set 
2 mixed model with repeated measures (MMRM) was used; Results are for the Randomized Set 
ASDAS-MI = Ankylosing Spondylitis Disease Activity Score-Major Improvement; ASAS: Assessment of Sponyloarthritis international 
Society; ASAS40= ASAS40% response criteria; SE = Standard error;  
Note: ASDAS major improvement is defined as a reduction from Baseline ≥2.0.  
Note: Part A Baseline was used as a reference to define ASDAS clinical improvement variables and ASAS variables  
* Nominal p<0.001, CIMZIA vs. placebo 

 

Inhibition of inflammation in Magnetic Resonance imaging (MRI) 
In Part B, signs of inflammation were assessed by MRI at Week 48 and at Week 96 and expressed as 
change from baseline in SIJ SPARCC and ASspiMRI-a score in the Berlin modifications. Patients who 
were in sustained remission at Week 48 had no or very low inflammation, and no meaningful increase 
in inflammation was observed at Week 96 irrespective of their treatment group. 
 
Retreatment in patients that experience a flare 
In Part B, 70% (73/104) placebo-treated patients, 14% (15/105) patients treated with Cimzia 200 mg 
every 4 weeks and 6.7% (7/104) patients treated with Cimzia 200 mg every 2 weeks experienced a flare 
and were subsequently treated with Cimzia 200 mg every 2 weeks.  
Among the 15 patients who flared in the group allocated to Cimzia 200 mg every 4 weeks, all patients 
completed 12 weeks of rescue therapy with Cimzia and had available ASDAS data, out of which 12 
(80%) had ASDAS Low or Inactive disease (i.e. all ASDAS <2.1) after 12 weeks of restarting the open-
label treatment. 
Among the 73 patients who flared in the group allocated to treatment withdrawal, 71 patients completed 
12 weeks of rescue therapy with Cimzia and had available ASDAS data, out of which 64 (90%) had 
ASDAS Low or Inactive disease (i.e. all ASDAS < 2.1) after 12 weeks of restarting the open-label 
treatment.  
Based on the results from C-OPTIMISE, a dose reduction in patients in sustained remission after one 
year of treatment with Cimzia may be considered (see section 4.2). Withdrawal of Cimzia treatment is 
associated with a high risk of flare. 
 
Non-radiographic axial spondyloarthritis (nr-axSpA) 
The efficacy and safety of Cimzia were assessed in a 52 weeks multicenter, randomized, double-blind, 
placebo-controlled study (AS0006) in 317 patients ≥18 years of age with adult-onset axial 



23 

spondyloarthritis and back pain for at least 12 months. Patients had to fulfil ASAS criteria for nr- 
axSpA (not including family history and good response to NSAIDs), and have had objective signs of 
inflammation indicated by C-reactive protein (CRP) levels above the upper limit of normal and/or 
sacroiliitis on magnetic resonance imaging (MRI), indicative of inflammatory disease [positive CRP 
(> ULN) and/or positive MRI], but without definitive radiographic evidence of structural damage on 
sacroiliac joints. Patients had active disease as defined by the BASDAI ≥4, and spinal pain ≥4 on 
a 0 to 10 NRS. Patients must have been intolerant to or had an inadequate response to at least two 
NSAIDs. Patients were treated with placebo or a loading dose of Cimzia 400 mg at 
Weeks 0, 2 and 4 followed by 200 mg of Cimzia every 2 weeks. Utilization and dose adjustment of 
standard of care medication (SC) (e.g., NSAIDs, DMARDs, corticosteroids, analgesics) were 
permitted at any time. The primary efficacy variable was the Ankylosing Spondylitis Disease Activity 
Score major improvement (ASDAS-MI) response at Week 52. ASDAS-MI response was defined as an 
ASDAS reduction (improvement) ≥ 2.0 relative to baseline or as reaching the lowest possible score. 
ASAS 40 was a secondary endpoint.  
At baseline, 37 % and 41% of patients had high disease activity (ASDAS ≥2.1, ≤3.5) and 62% and 
58% of patient had very high disease activity (ASDAS >3.5) in the CIMZIA group and placebo group 
respectively.  
 
Clinical response 
Study AS0006, performed in subjects without radiographic signs of inflammation in the SI joints, 
confirmed the effect previously demonstrated in this subgroup in the AS001 study.  
At Week 52, a statistically significant greater proportion of patients treated with Cimzia achieved 
ASDAS-MI response compared to patients treated with placebo. Cimzia-treated patients also had 
improvements compared to placebo in multiple components of axial spondyloarthritis disease activity, 
including CRP. At both Week 12 and 52, ASAS 40 responses were significantly greater than placebo. 
Key results are presented in Table 10. 
 
Table 10: ASDAS-MI and ASAS 40 responses in AS0006 (percent of patients) 

Parameters Placebo N=158 
Cimziaa 200 mg every 2 weeks 
N=159 

ASDAS-MI  
Week 52 

 
7% 
 

 
47%* 

ASAS 40 
Week 12 
 
Week 52 

 
11% 
 
16% 

 
48%* 
 
57%* 

a Cimzia administered every 2 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4 
* p<0.001 
All percents reflect the proportion of patients who responded in the full analysis set.  
 
At Week 52, the percentage of patients achieving ASDAS inactive disease (ASDAS < 1.3) was 36.4 % 
for the Cimzia group compared to 11.8 % for the placebo group. 

 
At Week 52, patients treated with Cimzia showed a clinical meaningful improvement in the MASES 
compared to placebo (LS mean change from baseline -2.4; -0.2 respectively).  
 
Psoriatic arthritis 
The efficacy and safety of Cimzia were assessed in a multicentre, randomised, double-blind, placebo 
controlled clinical trial (PsA001) in 409 patients ≥ 18 years of age with adult-onset active psoriatic 
arthritis for at least 6 months as defined by the Classification Criteria for Psoriatic Arthritis 
(CASPAR) criteria. Patients had ≥ 3 swollen and tender joints and increased acute phase reactants. 
Patients also had active psoriatic skin lesions or a documented history of psoriasis and had failed 1 or 
more DMARDs. Previous treatment with one TNF-antagonist was allowed and 20% of patients had 
prior TNF-antagonist exposure. Patients received a loading dose of Cimzia 400 mg at 
Weeks 0, 2 and 4 (for both treatment arms) or placebo followed by either Cimzia 200 mg 



24 

every 2 weeks or 400 mg every 4 weeks or placebo every 2 weeks. Patients receiving concomitant 
NSAIDs and conventional DMARDs were 72.6% and 70.2% respectively. The two primary endpoints 
were the percentage of patients achieving ACR 20 response at Week 12 and change from baseline in 
modified Total Sharp Score (mTSS) at Week 24. Efficacy and safety of Cimzia in patients with PsA 
whose predominant symptoms were sacroiliitis or axial spondyloarthritis have not been separately 
analysed. 
The 24-week double-blind placebo controlled treatment period of the study was followed by 
a 24-week dose-blind treatment period and an 168-week open-label treatment period. The maximum 
duration of the study was 216 weeks. All patients received Cimzia in both the dose-blind and open-
label follow-up periods. A total of 264 subjects (64.5%) completed the study through Week 216. 
 
ACR response 
Cimzia-treated patients had a statistically significant higher ACR 20 response rate at Week 12 and 
Week 24 compared with placebo-treated patients (p<0.001). The percentage of ACR 20 responders 
was clinically relevant for the Cimzia 200 mg every 2 weeks and Cimzia 400 mg every 4 weeks 
treatment groups compared to placebo group at every visit after baseline through Week 24 (nominal 
p≤0.001 at each visit). Cimzia treated patients also had significant improvements in 
ACR 50 and 70 response rates. At week 12 and 24 improvements in parameters of peripheral activity 
characteristic of psoriatic arthritis (e.g. number of swollen joints, number of painful/tender joints, 
dactylitis and enthesitis) were seen in the Cimzia-treated patients (nominal p-value p<0.01).  
Key efficacy outcomes from the PsA001 clinical trial are shown in Table 11. 
 
Table 11: Key efficacy outcomes in PsA001 clinical trial (percent of patients) 
Response Placebo 

 
N=136 

Cimzia(a)200 mg 
Q2W 
N=138 

Cimzia(b) 400 mg 
Q4W 
N=135 

ACR20 
Week 12 
Week 24 

 
24% 
24% 

 
58%** 
64%** 

 
52%** 
56%** 

ACR50 
Week 12 
Week 24 

 
11% 
13% 

 
36%** 
44%** 

 
33%** 
40%** 

ACR70 
Week 12 
Week 24 

 
3% 
4% 

 
25%** 
28%** 

 
13%* 
24%** 

Response Placebo 
 

N=86 

Cimzia(a)200 mg 
Q2W 
N=90 

Cimzia(b) 400 mg 
Q4W 
N=76 

PASI 75 (c) 
Week 12 
Week 24 
Week 48 

 
14% 
15% 
N/A 

 
47%*** 
62%*** 
67% 

 
47%*** 
61%*** 
62% 

(a) Cimzia administered every 2 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4 
(b) Cimzia administered every 4 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4 
(c) In subjects with at least 3% psoriasis BSA at Baseline 
*p<0.01, Cimzia vs placebo 
**p<0.001, Cimzia vs placebo  
***p<0.001(nominal), Cimzia vs placebo  
Results are from the randomized set.Treatment Difference: Cimzia 200 mg-placebo, Cimzia 400 mg-  
placebo (and corresponding 95% CI and p-value) are estimated using a standard two-sided Wald 
asymptotic standard errors test. Non-responder Imputation (NRI) is used for patients who escaped 
therapy or had missing data. 

 
Among 273 patients initially randomised to Cimzia 200 mg every 2 weeks and Cimzia 400 mg 
every 4 weeks, 237 (86.8%) were still on this treatment at Week 48. Of the 138 patients randomised to 
Cimzia 200 mg every 2 weeks, 92, 68 and 48 had an ACR 20/50/70 response, at Week 48, 



25 

respectively. Of the 135 patients randomised to Cimzia 400 mg every 4 weeks, 89, 62 and 41 patients 
had an ACR 20/50/70 response, respectively.  
 
Among patients remaining in the study, ACR 20, 50 and 70 response rates were maintained through 
Week 216. This was also the case for the other parameters of peripheral activity (e.g. number of 
swollen joints, number of painful/tender joints, dactylitis and enthesitis).  
 
Radiographic response 
In PsA001 clinical trial, inhibition of progression of structural damage was assessed radiographically 
and expressed as the change in modified total Sharp score (mTSS) and its components, the Erosion 
Score (ES) and Joint Space Narrowing score (JSN) at Week 24, compared to baseline. The mTSS 
Score was modified for psoriatic arthritis by addition of hand distal interphalangeal joints. Cimzia 
treatment inhibited the radiographic progression compared with placebo treatment at Week 24 as 
measured by change from baseline in total mTSS Score (LS mean [±SE] score was 0.28 [±0.07] in the 
placebo group compared with 0.06 [±0.06] in the Cimzia all doses group; p=0.007). Inhibition of 
radiographic progression was maintained with Cimzia treatment up to Week 48 in the subset of 
patients at higher risk of radiographic progression (patients with a Baseline mTSS score of > 6). 
Inhibition of radiographic progression was further maintained up to Week 216 for the patients who 
remained in the study. 
 
Physical function response and health-related outcomes 
In PsA001 clinical trial, Cimzia-treated patients reported significant improvements in physical 
function as assessed by the Health Assessment Questionnaire – Disability Index (HAQ-DI), in pain as 
assessed by the PAAP and in tiredness (fatigue) as reported by the Fatigue Assessment Scale (FAS) as 
compared to placebo. Cimzia-treated patients reported significant improvements in health-related 
quality of life as measured by the psoriatic arthritis QoL (PsAQoL) and the SF-36 Physical and Mental 
Components and in psoriatic arthritis-related productivity at work and within household, as reported 
by the Work Productivity Survey compared to placebo. Improvements in all afore-mentioned 
outcomes were maintained through Week 216.  
 
Plaque psoriasis 
The efficacy and safety of Cimzia were assessed in two placebo-controlled studies (CIMPASI-1 and 
CIMPASI-2) and one placebo- and active-controlled study (CIMPACT) in patients ≥18 years of age 
with moderate to severe chronic plaque psoriasis for at least 6 months. Patients had a Psoriasis Area 
and Severity Index (PASI) score ≥ 12, body surface area (BSA) involvement of ≥ 10%, Physician 
Global Assessment (PGA) of ≥ 3, and were candidates for systemic therapy and/or phototherapy 
and/or chemophototherapy. Patients who were ‘primary’ non-responders on any prior biologic therapy 
(defined as no response within the first 12 weeks of treatment) were excluded from the phase III 
studies (CIMPASI-1, CIMPASI-2 and CIMPACT). The efficacy and safety of Cimzia were evaluated 
versus etanercept in the CIMPACT study. 
 
In studies CIMPASI-1 and CIMPASI-2 the co-primary efficacy endpoints were the proportion of 
patients achieving PASI 75 and PGA “clear” or “almost clear” (with at least a 2-point reduction from 
baseline) at Week 16. In the CIMPACT study, the primary efficacy endpoint was the proportion of 
patients achieving PASI 75 at Week 12. PASI75 and PGA at Week 16 were key secondary endpoints. 
PASI 90 at Week 16 was a key secondary endpoint in all 3 studies.  
 
CIMPASI-1 and CIMPASI-2 evaluated 234 patients and 227 patients respectively. In both studies 
patients were randomized to receive placebo or Cimzia 200 mg every 2 weeks (following a loading 
dose of Cimzia 400 mg at Weeks 0, 2 and 4) or Cimzia 400 mg every 2 weeks. At week 16, patients 
randomized to Cimzia who achieved a PASI 50 response continued to receive Cimzia up to 
Week 48 at the same randomized dose. Patients originally randomized to placebo that achieved a 
PASI 50 response but not a PASI 75 response at Week 16 received Cimzia 200 mg every 2 weeks 
(with a loading dose of Cimzia 400 mg at Weeks 16, 18, and 20). Patients with an inadequate response 
at Week 16 (PASI 50 non-responders) were eligible to receive Cimzia 400 mg every 2 weeks in an 
open-label manner for a maximum of 128 weeks. 
 



26 

The CIMPACT study evaluated 559 patients. Patients were randomized to receive placebo, or 
Cimzia 200 mg every 2 weeks (following a loading dose of Cimzia 400 mg at Weeks 0, 2 and 4), or 
Cimzia 400 mg every 2 weeks up to Week 16, or etanercept 50 mg twice weekly, up to Week 12. 
Patients originally randomized to Cimzia who achieved a PASI75 response at Week 16 were re-
randomized based on their original dosing schedule. Patients on Cimzia 200 mg every 2 weeks were 
re-randomized to Cimzia 200 mg every 2 weeks, Cimzia 400 mg every 4 weeks or placebo. Patient on 
Cimzia 400 mg every 2 weeks were re-randomized to Cimzia 400 mg every 2 weeks, Cimzia 200 mg 
every 2 weeks, or placebo. Patients were evaluated in a double-blind placebo-controlled manner 
through Week 48. All subjects who did not achieve a PASI 75 response at Week 16 entered an escape 
arm and received Cimzia 400 mg every 2 weeks in an open-label manner for a maximum of 128 
weeks. 
 
In all three studies, the blinded 48-week maintenance period was followed by a 96-week open-label 
treatment period for the patients who were PASI 50 responders at Week 48. All these patients, 
including those receiving Cimzia 400 mg every 2 weeks, started the open-label period at Cimzia 200 
mg every 2 weeks.  
 
Patients were predominantly men (64%) and Caucasian (94%), with a mean age of 45.7 years 
(18 to 80 years); of these, 7.2% were ≥ 65 years of age. Of the 850 patients randomized to receive 
placebo or Cimzia in these placebo-controlled studies, 29% of patients were naïve to prior systemic 
therapy for the treatment of psoriasis. 47% had received prior phototherapy or chemophototherapy, 
and 30% had received prior biologic therapy for the treatment of psoriasis. Of the 850 patients, 14% 
had received at least one TNF-antagonist, 13% had received an anti-IL-17, and 5% had received an 
anti-IL 12/ 23. Eighteen percent of patients reported a history of psoriatic arthritis at baseline. The 
mean PASI score at baseline was 20 and ranged from 12 to 69. The baseline PGA score ranged from 
moderate (70%) to severe (30%). Mean baseline BSA was 25% and ranged from 10% to 96%. 
 
Clinical response at Week 16 and 48 
The key results of CIMPASI-1 and CIMPASI-2 studies are presented in Table 12. 
 
Table 12 Clinical response in studies CIMPASI-1 and CIMPASI-2 at Week 16 and Week 48 
 Week 16 Week 48 
CIMPASI-1 
 Placebo 

 
N=51 

Cimzia 200 mg 
Q2W a) 
N=95 

Cimzia 400 mg 
Q2W 
N=88 

Cimzia 200 mg 
Q2W 
N=95 

Cimzia 400 mg 
Q2W 
N=88 

PGA clear or 
almost clearb) 

4.2% 47.0%* 57.9%* 52.7% 69.5% 

PASI 75 6.5% 66.5%* 75.8%* 67.2% 87.1% 
PASI 90 0.4% 35.8%* 43.6%* 42.8% 60.2% 
CIMPASI-2 
 Placebo 

 
N=49 

Cimzia 200 mg 
Q2W a) 
N=91 

Cimzia 400 mg 
Q2W 
N=87 

Cimzia 200 mg 
Q2W 
N= 91 

Cimzia 400 mg 
Q2W 
N= 87 

PGA clear or 
almost clearb) 

2.0% 66.8%* 71.6%* 72.6% 66.6% 

PASI 75 11.6% 81.4%* 82.6%* 78.7% 81.3% 
PASI 90 4.5% 52.6%* 55.4%* 59.6% 62.0% 
a) Cimzia 200 mg administered every 2 weeks preceded by a loading dose of 400 mg at Week 0, 2, 4. 
b) PGA 5 category scale. Treatment success of “clear” (0) or “almost clear”(1) consisted of no signs of 
psoriasis or normal to pink coloration of lesions, no thickening of the plaque, and none to minimal 
focal scaling. 
* Cimzia vs placebo: p< 0.0001.  
Response rates and p-values for PASI and PGA were estimated based on a logistic regression model 
where missing data were imputed using multiple imputation based on the MCMC method. Subject 
who escaped or withdrew (based on not achieving PASI 50 response) were treated as non-responders 
at Week 48. 



27 

Results are from the Randomized Set. 
 
The key results of the CIMPACT trial are presented in Table 13. 
 
Table 13  Clinical response in CIMPACT study at Week 12 and Week 16 
 Week 12 Week 16 
 Placebo 

N=57 
Cimzia 200 
mg Q2W a) 

N=165 

Cimzia 400 
mg Q2W 
N=167 

Etanercept 5
0 mg BiW 

N=170 

Placebo 
N=57 

Cimzia 200 
mg Q2W 
N=165 

Cimzia 400 
mg 

Q2W 
N=167 

PASI 75 5% 61.3%*,§ 66.7%*,§§ 53.3% 3.8% 68.2%* 74.7%* 
PASI 90 0.2% 31.2%* 34.0%* 27.1% 0.3% 39.8%* 49.1%* 
PGA clear or 
almost clear b) 1.9% 39.8%** 50.3%* 39.2% 3.4% 48.3%* 58.4%* 
a) Cimzia 200 mg administered every 2 weeks preceded by a loading dose of 400 mg at Week 0, 2, 4. 
b) PGA 5 category scale. Treatment success of “clear” (0) or “almost clear”(1) consisted of no signs of 
psoriasis or normal to pink coloration of lesions, no thickening of the plaque, and none to minimal 
focal scaling. 
* Cimzia vs placebo: p< 0.0001.  
§ Cimzia 200 mg every 2 weeks versus etanercept 50 mg twice weekly demonstrated non-inferiority 
(difference between etanercept and Cimzia 200 mg every 2 weeks was 8.0%, 95% CI -2.9, 18.9, based 
on a pre-specified non-inferiority margin of 10%). 
§§ Cimzia 400 mg every 2 weeks versus etanercept 50 mg twice weekly demonstrated superiority 
(p<0.05) 
** Cimzia vs Placebo p < 0.001. Response rates and p-values based on a logistic regression model.  
Missing data were imputed using multiple imputation based on the MCMC method. Results are from 
the Randomized Set. 
 
In all 3 studies, the PASI 75 response rate was significantly greater for Cimzia compared to placebo 
starting at Week 4. 
 
Both doses of Cimzia demonstrated efficacy compared to placebo regardless of age, gender, body 
weight, BMI, psoriasis disease duration, previous treatment with systemic therapies and previous 
treatment with biologics.  
 
Maintenance of response  
In an integrated analysis of  CIMPASI-1 and CIMPASI-2, among patients who were PASI 75 
responders at Week 16 and received Cimzia 400 mg every 2 weeks (N=134 of 175 randomised 
subjects) or Cimzia 200 mg every 2 weeks (N=132 of 186 randomised subjects), the maintenance of 
response at Week 48 was 98.0% and 87.5%, respectively. Among patients who were PGA clear or 
almost clear at Week 16 and received Cimzia 400 mg every 2 weeks (N=103 of 175) or Cimzia 200 
mg every 2 weeks (N=95 of 186), the maintenance of response at Week 48 was 85.9% and 84.3% 
respectively. 
 
After an additional 96 weeks of open-label treatment (Week 144) the maintenance of response was 
evaluated. Twenty-one percent of all randomised subjects were lost to follow-up before Week 144. 
Approximately 27% of completer study subjects who entered the open-label treatment between weeks 
48 to 144 on Cimzia 200 mg every 2 weeks had their dose increased to Cimzia 400 mg every 2 weeks 
for maintenance of response. In an analysis in which all patients with treatment failures were 
considered non-responders, the maintenance of response of the Cimzia 200 mg every 2 weeks 
treatment group for the respective endpoint, after an additional 96 weeks of open-label therapy, was 
84.5% for PASI 75 for study subjects who were responders at Week 16  and 78.4% for PGA clear or 
almost clear. The maintenance of response of the Cimzia 400 mg every 2 weeks treatment group, who 
entered the open-label period at Cimzia 200 mg every 2 weeks, was 84.7% for PASI 75 for study 
subjects who were responders at Week 16 and 73.1% for PGA clear or almost clear.  
 



28 

These response rates were based on a logistic regression model where missing data were imputed over 
48 or 144 weeks using multiple imputation (MCMC method) combined with NRI for treatment 
failures.  
 
In the CIMPACT study, among PASI 75 responders at Week 16 who received Cimzia 400 mg every 2 
weeks and were re-randomized to either Cimzia 400 mg every 2 weeks, Cimzia 200 mg every 2 
weeks, or placebo, there was a higher percentage of PASI 75 responders at Week 48 in the Cimzia 
groups as compared to placebo (98.0%, 80.0%, and 36.0%, respectively). Among PASI75 responders 
at Week 16 who received Cimzia 200 mg every 2 weeks and were re-randomized to either Cimzia 400 
mg every 4 weeks, Cimzia 200 mg every 2 weeks, or placebo, there was also a higher percentage of 
PASI 75 responders at Week 48 in the Cimzia groups as compared to placebo (88.6%, 79.5%, and 
45.5%, respectively). Non-responder imputation was used for missing data. 
 
Quality of life / Patient reported outcomes 
 
Statistically significant improvements at Week 16 (CIMPASI-1 and CIMPASI-2) from baseline 
compared to placebo were demonstrated in the DLQI (Dermatology Life Quality Index). Mean 
decreases (improvements) in DLQI from baseline ranged from -8.9 to -11.1 with Cimzia 200 mg every 
2 weeks, from -9.6 to -10.0 with Cimzia 400 mg every 2 weeks, versus -2.9 to -3.3 for placebo at 
Week 16.  
 
In addition, at Week 16, Cimzia treatment was associated with a greater proportion of patients 
achieving a DLQI score of  0 or 1 (Cimzia 400 mg every 2 weeks, 45.5% and 50.6% respectively; 
Cimzia 200 mg every 2 weeks, 47.4% and 46.2% respectively, versus placebo, 5.9% and 8.2% 
respectively).  
 
Improvements in DLQI score were sustained or slightly decreased through Week 144. 
 
Cimzia-treated patients reported greater improvements compared to placebo in the Hospital Anxiety 
and Depression Scale (HADS)-D. 
 
Immunogenicity 
 
The data below reflect the percentage of patients whose test results were considered positive for 
antibodies to certolizumab pegol in an ELISA and later in a more sensitive method, and are highly 
dependent on the sensitivity and specificity of the assay.  The observed incidence of antibody 
(including neutralizing antibody) positivity in an assay is highly dependent on several factors, 
including assay sensitivity and specificity, assay methodology, sample handling, timing of sample 
collection, concomitant medications, and underlying disease. For these reasons, comparison of the 
incidence of antibodies to certolizumab pegol in the studies described below with the incidence of 
antibodies in other studies or to other products may be misleading. 
 
Rheumatoid arthritis 
The overall percentage of patients with antibodies to Cimzia detectable on at least 1 occasion 
was 9.6% in RA placebo-controlled trials. Approximately one-third of antibody-positive patients had 
antibodies with neutralising activity in vitro. Patients treated with concomitant immunosuppressants 
(MTX) had a lower rate of antibody development than patients not taking immunosuppressants at 
baseline. Antibody formation was associated with lowered drug plasma concentration and in some 
patients, reduced efficacy. 
 
In 2 long-term (up to 5 years of exposure) open-label studies, the overall percentage of patients with 
antibodies to Cimzia detectable on at least one occasion was 13% (8.4% of the overall patients had 
transient formation of antibodies and an additional 4.7% had persistent formation of antibodies to 
Cimzia). The overall percentage of patients that were antibody positive with a persistent reduction of 
drug plasma concentration was estimated to be 9.1%. Similar to the placebo-controlled studies, 
antibody positivity was associated with reduced efficacy in some patients. 



29 

 
A pharmacodynamic model based on the Phase III trial data predicts that around 15% of the patients 
develop antibodies in 6 months at the recommended dose regimen (200 mg every 2 weeks following a 
loading dose) without MTX co-treatment. This number decreases with increasing doses of 
concomitant MTX treatment. These data are reasonably in agreement with observed data. 
 
Psoriatic arthritis 
The overall percentage of patients with antibodies to Cimzia detectable on at least one occasion up to 
Week 24 was 11.7% in the Phase III placebo-controlled trial in patients with psoriatic arthritis. 
Antibody formation was associated with lowered drug plasma concentration.  
 
Over the course of the entire study (up to 4 years of exposure), the overall percentage of patients with 
antibodies to Cimzia detectable on at least one occasion was 17.3% (8.7% had transient formation and 
an additional 8.7% had persistent formation of antibodies to Cimzia). The overall percentage of 
patients that were antibody positive with a persistent reduction of drug plasma concentration was 
estimated to be 11.5%. 
 
Plaque psoriasis 
In the Phase III placebo- and active-controlled studies, the percentages of patients who were positive 
for antibodies to Cimzia on at least one occasion during treatment up to Week 48 were 8.3 % (22/265) 
and 19.2% (54/281) for the Cimzia 400 mg every 2 weeks and Cimzia 200 mg every 2 weeks 
respectively. In CIMPASI-1 and CIMPASI-2, sixty patients were antibody positive, 27 of these 
patients were evaluable for neutralizing antibodies and tested positive. First occurrences of antibody 
positivity in the open-label treatment period were observed in 2.8% (19/668) of patients. Antibody 
positivity was associated with lowered drug plasma concentration and in some patients with reduced 
efficacy. 
 
Axial spondyloarthritis 
AS001 
The overall percentage of patients with antibodies to Cimzia detectable on at least one occasion up to 
Week 24 was 4.4% in the AS001 phase III placebo-controlled trial in patients with axial 
spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis 
subpopulations). Antibody formation was associated with lowered drug plasma concentration. 

Over the course of the entire study (up to 192 weeks), the overall percentage of patients with 
antibodies to Cimzia detectable on at least one occasion was 9.6% (4.8% had transient formation and 
an additional 4.8% had persistent formation of antibodies to Cimzia). The overall percentage of 
patients that were antibody positive with a persistent reduction of drug plasma concentration was 
estimated to be 6.8%. 
 
AS0006 and C-OPTIMISE  
A more sensitive and drug tolerant assay was used for the first time in the AS0006 study (and later 
also in the C-OPTIMISE study), resulting in a greater proportion of samples having measurable 
antibodies to Cimzia and thus a greater incidence of patients being classed as antibody positive. In 
AS0006,  the overall incidence of patients who were antibody positive to Cimzia was 97% 
(248/255 patients) after up to 52 weeks of treatment. Only the highest titers were associated with 
reduced Cimzia plasma levels, however, no impact on efficacy was observed. Similar results in 
relation to antibodies to Cimzia were seen in C-OPTIMISE. Results from C-OPTIMISE also indicated 
that a reduction of the dose to Cimzia 200 mg every 4 weeks did not change immunogenicity 
outcomes. 
 
About 22% (54/248) of the patients in AS0006 who were anti-Cimzia antibody positive at any time, 
had antibodies that were classified as neutralizing. The neutralizing status of antibodies in C-
OPTIMISE was not assessed.  
 



30 

5.2 Pharmacokinetic properties 
 
Certolizumab pegol plasma concentrations were broadly dose-proportional. Pharmacokinetics 
observed in patients with rheumatoid arthritis and psoriasis were consistent with those seen in healthy 
subjects. 
 
Absorption 
Following subcutaneous administration, peak plasma concentrations of certolizumab pegol were 
attained between 54 and 171 hours post-injection. Certolizumab pegol has a bioavailability (F) of 
approximately 80% (range 76% to 88%) following subcutaneous administration compared to 
intravenous administration. 
 
Distribution 
The apparent volume of distribution (V/F) was estimated at 8.01 l in a population pharmacokinetic 
analysis of patients with rheumatoid arthritis and at 4.71 l in a population pharmacokinetic analysis of 
patients with plaque psoriasis. 
 
Biotransformation and elimination 
PEGylation, the covalent attachment of PEG polymers to peptides, delays the elimination of these 
entities from the circulation by a variety of mechanisms, including decreased renal clearance, 
decreased proteolysis, and decreased immunogenicity. Accordingly, certolizumab pegol is an antibody 
Fab' fragment conjugated with PEG in order to extend the terminal plasma elimination half-life of the 
Fab' to a value comparable with a whole antibody product. The terminal elimination phase half-life 
(t1/2) was approximately 14 days for all doses tested.  
 
Clearance following subcutaneous dosing was estimated to be 21.0 ml/h in a rheumatoid arthritis 
population pharmacokinetic analysis, with an inter-subject variability of 30.8% (CV) and an inter-
occasion variability of 22.0%. When assessed using the previous ELISA method, the presence of 
antibodies to certolizumab pegol resulted in an approximately three-fold increase in clearance. 
Compared with a 70 kg person, clearance is 29% lower and 38% higher, respectively, in individual RA 
patients weighing 40 kg and 120 kg. The clearance following subcutaneous dosing in patients with 
psoriasis was 14 ml/h with an inter-subject variability of 22.2% (CV). 
 
The Fab' fragment comprises protein compounds and is expected to be degraded to peptides and amino 
acids by proteolysis. The de-conjugated PEG component is rapidly eliminated from plasma and is to 
an unknown extent excreted renally. 
 
Special populations 
Renal impairment 
Specific clinical trials have not been performed to assess the effect of renal impairment on the 
pharmacokinetics of certolizumab pegol or its PEG fraction. However, population pharmacokinetic 
analysis based on subjects with mild renal impairment showed no effect of creatinine clearance. There 
are insufficient data to provide a dosing recommendation in moderate and severe renal impairment. 
The pharmacokinetics of the PEG fraction of certolizumab pegol are expected to be dependent on 
renal function but have not been assessed in patients with renal impairment. 
 
Hepatic impairment 
Specific clinical trials have not been performed to assess the effect of hepatic impairment on the 
pharmacokinetics of certolizumab pegol. 
 
Elderly patients (≥ 65 years old) 
Specific clinical trials have not been performed in elderly patients subjects. However, no effect of age 
was observed in a population pharmacokinetic analysis in patients with rheumatoid arthritis in 
which 78 subjects (13.2% of the population) were aged 65 or greater and the oldest subject was 
aged 83 years. No effect of age was observed in a population pharmacokinetic analysis in adult 
patients with plaque psoriasis. 
 



31 

Gender 
There was no effect of gender on the pharmacokinetics of certolizumab pegol. As clearance decreases 
with decreasing body weight, females may generally obtain somewhat higher systemic exposure of 
certolizumab pegol. 
 
Pharmacokinetic/pharmacodynamic relationship 
On the basis of Phase II and Phase III clinical trial data in patients with rheumatoid arthritis, a 
population exposure-response relationship was established between average plasma concentration of 
certolizumab pegol during a dosing interval (Cavg) and efficacy (ACR 20 responder definition). The 
typical Cavg that produces half the maximum probability of ACR 20 response (EC50) was 17 µg/ml 
(95% CI: 10-23 µg/ml). Similarly, on the basis of Phase III clinical trial data in patients with psoriasis, 
a population exposure-response relationship was established between plasma concentration of 
certolizumab pegol and PASI with an EC90 of 11.1 µg/ml. 
 
5.3 Preclinical safety data 
 
The pivotal non-clinical safety studies were conducted in the cynomolgus monkey. In rats and 
monkeys, at doses higher than those given to humans, histopathology revealed cellular vacuolation, 
present mainly in macrophages, in a number of organs (lymph nodes, injection sites, spleen, adrenal, 
uterine, cervix, choroid plexus of the brain, and in the epithelial cells of the choroid plexus). It is likely 
that this finding was caused by cellular uptake of the PEG moiety. In vitro functional studies of human 
vacuolated macrophages indicated all functions tested were retained. Studies in rats indicated that 
> 90% of the administered PEG was eliminated in 3 months following a single dose, with the urine 
being the main route of excretion. 
 
Certolizumab pegol does not cross-react with rodent TNF. Therefore, reproductive toxicology studies 
have been performed with a homologous reagent recognising rat TNF. The value of these data to the 
evaluation of human risk may be limited. No adverse effects were seen on maternal well-being or 
female fertility, embryo-foetal and peri- and post-natal reproductive indices in rats using a rodent anti-
rat TNFα PEGylated Fab' (cTN3 PF) following sustained TNFα suppression. In male rats, reduced 
sperm motility and a trend of reduced sperm count were observed. 
 
Distribution studies have demonstrated that placental and milk transfer of cTN3 PF to the foetal and 
neonatal circulation is negligible. Certolizumab pegol does not bind to the human neonatal Fc receptor 
(FcRn). Data from a human closed-circuit placental transfer model ex vivo suggest low or negligible 
transfer to the foetal compartment. In addition, experiments of FcRn-mediated transcytosis in cells 
transfected with human FcRn showed negligible transfer (see section 4.6).  
 
No mutagenic or clastogenic effects were demonstrated in preclinical studies. Carcinogenicity studies 
have not been performed with certolizumab pegol. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium acetate 
Sodium chloride 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 



32 

6.3 Shelf life 
 
2 years. 
See also section 6.4 for shelf-life related to storage at room temperature up to a maximum of 25°C. 
 
6.4 Special precautions for storage 
 
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. 
The pre-filled syringes may be stored at room temperature (up to 25°C) for a single period of 
maximum 10 days with protection from light. At the end of this period the pre-filled syringes must be 
used or discarded. 
 
6.5 Nature and contents of container 
 
One ml pre-filled syringe (type I glass) with a plunger stopper (bromobutyl rubber), 
containing 200 mg of certolizumab pegol. The needle shield is styrene butadiene rubber which 
contains a derivative of natural rubber latex (see section 4.4). 
 
Pack size of 2 pre-filled syringes and 2 alcohol wipes. 
Multipack containing 6 (3 packs of 2) pre-filled syringes and 6 (3 packs of 2) alcohol wipes. 
Multipack containing 10 (5 packs of 2) pre-filled syringes and 10 (5 packs of 2) alcohol wipes. 
Pack size of 2 pre-filled syringes with needle guard and 2 alcohol wipes (for use by healthcare 
professionals only). 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Comprehensive instructions for the preparation and administration of Cimzia in a pre-filled syringe are 
given in the package leaflet. 
This medicinal product is for single use only. Any unused product or waste material should be 
disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
B-1070 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/001  
EU/1/09/544/002  
EU/1/09/544/003  
EU/1/09/544/004  
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 01 October 2009 
Date of latest renewal: 16 May 2014 
 



33 

 
10. DATE OF REVISION OF THE TEXT 
 
{MM/YYYY} 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu



34 

1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in pre-filled pen 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each pre-filled pen contains 200 mg certolizumab pegol in one ml. 
 
Certolizumab pegol is a recombinant, humanised antibody Fab' fragment against tumour necrosis 
factor alpha (TNFα) expressed in Escherichia coli and conjugated to polyethylene glycol (PEG). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection (injection) 
 
Clear to opalescent, colourless to yellow solution. The pH of the solution is approximately 4.7. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Rheumatoid arthritis 
Cimzia, in combination with methotrexate (MTX), is indicated for: 
 the treatment of moderate to severe, active rheumatoid arthritis (RA) in adult patients when the 

response to disease-modifying antirheumatic drugs (DMARDs) including MTX, has been 
inadequate. Cimzia can be given as monotherapy in case of intolerance to MTX or when 
continued treatment with MTX is inappropriate 

 
 the treatment of severe, active and progressive RA in adults not previously treated with MTX or 

other DMARDs. 
 
Cimzia 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 MTX. 
 
Axial spondyloarthritis 
Cimzia is indicated for the treatment of adult patients with severe active axial spondyloarthritis, 
comprising:  
 
Ankylosing spondylitis (AS) (also known as radiographic axial spondyloarthritis) 
Adults with severe active ankylosing spondylitis who have had an inadequate response to, or are 
intolerant to nonsteroidal anti-inflammatory drugs (NSAIDs).  

 
Axial spondyloarthritis without radiographic evidence of AS (also known as non-radiographic axial 
spondyloarthritis) 
Adults with severe active axial spondyloarthritis without radiographic evidence of AS but with 
objective signs of inflammation by elevated C-reactive protein (CRP) and /or magnetic resonance 
imaging (MRI), who have had an inadequate response to, or are intolerant to NSAIDs. 
 
Psoriatic arthritis  
Cimzia, in combination with MTX, is indicated for the treatment of active psoriatic arthritis in adults 
when the response to previous DMARD therapy has been inadequate. 
 



35 

Cimzia can be given as monotherapy in case of intolerance to methotrexate or when continued 
treatment with methotrexate is inappropriate. 
 
Plaque psoriasis 
Cimzia is indicated for the treatment of moderate to severe plaque psoriasis in adults who are 
candidates for systemic therapy. 
 
For details on therapeutic effects, see section 5.1. 
 
4.2 Posology and method of administration 
 
Treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and 
treatment of conditions for which Cimzia is indicated. Patients should be given the special reminder 
card. 
 
Posology 
 
Rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, plaque psoriasis 
 
Loading dose 
The recommended starting dose of Cimzia for adult patients is 400 mg (given 
as 2 subcutaneous injections of 200 mg each) at weeks 0, 2 and 4. For rheumatoid arthritis and 
psoriatic arthritis, MTX should be continued during treatment with Cimzia where appropriate. 
 
Maintenance dose 
Rheumatoid arthritis 
After the starting dose, the recommended maintenance dose of Cimzia for adult patients with 
rheumatoid arthritis is 200 mg every 2 weeks. Once clinical response is confirmed, an alternative 
maintenance dosing of 400 mg every 4 weeks can be considered. MTX should be continued during 
treatment with Cimzia where appropriate. 
 
Axial spondyloarthritis 
After the starting dose, the recommended maintenance dose of Cimzia for adult patients with axial 
spondyloarthritis is 200 mg every 2 weeks or 400 mg every 4 weeks. After at least 1 year of treatment 
with Cimzia, in patients with sustained remission, a reduced maintenance dose of 200 mg every 4 
weeks may be considered (see section 5.1). 
  
Psoriatic arthritis 
After the starting dose, the recommended maintenance dose of Cimzia for adult patients with psoriatic 
arthritis is 200 mg every 2 weeks. Once clinical response is confirmed, an alternative maintenance 
dosing of 400 mg every 4 weeks can be considered. MTX should be continued during treatment with 
Cimzia where appropriate. 
 
For the above indications, available data suggest that clinical response is usually achieved 
within 12 weeks of treatment. Continued therapy should be carefully reconsidered in patients who 
show no evidence of therapeutic benefit within the first 12 weeks of treatment. 
 
Plaque psoriasis 
After the starting dose, the maintenance dose of Cimzia for adult patients with plaque psoriasis 
is 200 mg every 2 weeks. A dose of 400 mg every 2 weeks can be considered in patients with 
insufficient response (see section 5.1). 
 
Available data in adults with plaque psoriasis suggest that a clinical response is usually achieved 
within 16 weeks of treatment. Continued therapy should be carefully reconsidered in patients who 
show no evidence of therapeutic benefit within the first 16 weeks of treatment. Some patients with an 
initial partial response may subsequently improve with continued treatment beyond 16 weeks. 
 



36 

Missed dose 
Patients who miss a dose should be advised to inject the next dose of Cimzia as soon as they 
remember and then continue injecting subsequent doses as instructed. 
 
Special populations 
Paediatric population (< 18 years old) 
The safety and efficacy of Cimzia in children and adolescents below age 18 years have not yet been 
established. No data are available. 
 
Elderly patients (≥ 65 years old) 
No dose adjustment is required. Population pharmacokinetic analyses showed no effect of age (see 
section 5.2). 
 
Renal and hepatic impairment 
Cimzia has not been studied in these patient populations. No dose recommendations can be made (see 
section 5.2). 
 
Method of administration 
The total content (1 ml) of the pre-filled pen should be administered as a subcutaneous injection only. 
Suitable sites for injection would include the thigh or abdomen. 
 
After proper training in injection technique, patients may self-inject using the pre-filled pen if their 
physician determines that it is appropriate and with medical follow-up as necessary. The physician 
should discuss with the patient which injection presentation option is the most appropriate. 
 
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 or opportunistic infections (see 
section 4.4). 
 
Moderate to severe heart failure (NYHA classes 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 must be monitored closely for signs and symptoms of infections including tuberculosis before, 
during and after treatment with Cimzia. Because the elimination of certolizumab pegol may take up 
to 5 months, monitoring should be continued throughout this period (see section 4.3). 
 
Treatment with Cimzia must not be initiated in patients with a clinically important active infection, 
including chronic or localised infections, until the infection is controlled (see section 4.3).  
 
Patients who develop a new infection while undergoing treatment with Cimzia should be monitored 
closely. Administration of Cimzia should be discontinued if a patient develops a new serious infection 
until the infection is controlled. Physicians should exercise caution when considering the use of 
Cimzia in patients with a history of recurring or opportunistic infection or with underlying conditions 
which may predispose patients to infections, including the use of concomitant immunosuppressive 
medications. 
 
Patients with rheumatoid arthritis may not manifest typical symptoms of infection, including fever, 
due to their disease and concomitant medicinal products. Therefore, early detection of any infection, 



37 

particularly atypical clinical presentations of a serious infection, is critical to minimise delays in 
diagnosis and initiation of treatment. 
 
Serious infections, including sepsis and tuberculosis (including miliary, disseminated and 
extrapulmonary disease), and opportunistic infections (e.g. histoplasmosis, nocardia, candidiasis) have 
been reported in patients receiving Cimzia. Some of these events have been fatal. 
 
Tuberculosis 
Before initiation of therapy with Cimzia, all patients must be evaluated for both active or inactive 
(latent) tuberculosis infection. This evaluation should include a detailed medical history for patients 
with a personal history of tuberculosis, with possible previous exposure to others with active 
tuberculosis, and with previous and/or current use of immunosuppressive therapy. Appropriate 
screening tests, e.g. tuberculin skin test and chest X-ray, should be performed in all patients (local 
recommendations may apply). It is recommended that the conduct of these tests should be recorded in 
the patient's 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 prior to or during treatment, Cimzia therapy must not be initiated 
and must be discontinued (see section 4.3). 
 
If inactive (‘latent’) tuberculosis is suspected, a physician with expertise in the treatment of 
tuberculosis should be consulted. In all situations described below, the benefit/risk balance of Cimzia 
therapy should be very carefully considered. 
 
If latent tuberculosis is diagnosed, appropriate anti-tuberculosis therapy must be started before 
initiating treatment with Cimzia and in accordance with local recommendations.  
Use of anti-tuberculosis therapy should also be considered before the initiation of Cimzia in patients 
with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be 
confirmed, and in patients who have significant risk factors for tuberculosis despite a negative test for 
latent tuberculosis. Biological tests for tuberculosis screening should be considered before starting 
Cimzia treatment if there is any potential latent tuberculosis infection, regardless of BCG vaccination. 
 
Despite previous or concomitant prophylactic treatment for tuberculosis, cases of active tuberculosis 
have occurred in patients treated with TNF-antagonists including Cimzia. Some patients who have 
been successfully treated for active tuberculosis have redeveloped tuberculosis while being treated 
with Cimzia. 
 
Patients should be instructed to seek medical advice if signs/symptoms (e.g. persistent cough, 
wasting/weight loss, low grade fever, listlessness) suggestive of a tuberculosis infection occur during 
or after therapy with Cimzia. 
 
Hepatitis B virus (HBV) reactivation 
Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including certolizumab 
pegol, 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 Cimzia. For patients who 
test positive for HBV infection, consultation with a physician with expertise in the treatment of 
hepatitis B is recommended.  
 
Carriers of HBV who require treatment with Cimzia should be closely monitored for signs and 
symptoms of active HBV infection throughout therapy and for several months following termination 
of therapy. Adequate data of 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, Cimzia should be stopped and effective anti-viral therapy with 
appropriate supportive treatment should be initiated. 
 



38 

Malignancies and lymphoproliferative disorders 
The potential role of TNF-antagonist therapy in the development of malignancies is not known. 
Caution should be exercised when considering TNF-antagonist therapy for patients with a history of 
malignancy or when considering continuing treatment in patients who develop malignancy.  
 
With the current knowledge, a possible risk for the development of lymphomas, leukaemia or other 
malignancies in patients treated with a TNF-antagonist cannot be excluded. 
 
In clinical trials with Cimzia and other TNF-antagonists, more cases of lymphoma and other 
malignancies have been reported among patients receiving TNF-antagonists than in control patients 
receiving placebo (see section 4.8). 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. 
 
No trials have been conducted that include patients with a history of malignancy, or that continue 
treatment in patients who develop malignancy, while receiving Cimzia.  
 
Skin cancers 
Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-antagonists 
including certolizumab pegol (see section 4.8). Periodic skin examination is recommended, 
particularly for patients with risk factors for skin cancer. 
 
Paediatric malignancy 
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) 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. 
 
Post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL), have been reported in patients 
treated with TNF-antagonists. This rare type of T-cell lymphoma has a very aggressive disease course 
and is usually fatal. The majority of reported TNF-antagonist cases occurred in adolescent and young 
adult males with Crohn’s disease or ulcerative colitis. Almost all of these patients had received 
treatment with the immunosuppressants azathioprine and/or 6-mercaptopurine concomitantly with a 
TNF-antagonist at or prior to diagnosis. A risk for development of hepatosplenic T-cell lymphoma in 
patients treated with Cimzia cannot be excluded. 
 
Chronic obstructive pulmonary disease (COPD) 
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. 
 
Congestive heart failure 
Cimzia is contraindicated in moderate or severe heart failure (see section 4.3). 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 congestive heart failure have also been reported in 
rheumatoid arthritis patients receiving Cimzia. Cimzia should be used with caution in patients with 
mild heart failure (NYHA class I/II). Treatment with Cimzia must be discontinued in patients who 
develop new or worsening symptoms of congestive heart failure. 
 



39 

Haematological reactions 
Reports of pancytopaenia, including aplastic anaemia, have been rare with TNF-antagonists. Adverse 
reactions of the haematologic system, including medically significant cytopaenia (e.g. leukopaenia, 
pancytopaenia, thrombocytopaenia) have been reported with Cimzia (see section 4.8). All patients 
should be advised to seek immediate medical attention if they develop signs and symptoms suggestive 
of blood dyscrasias or infection (e.g., persistent fever, bruising, bleeding, pallor) while on Cimzia. 
Discontinuation of Cimzia therapy should be considered in patients with confirmed significant 
haematological abnormalities. 
 
Neurological events 
Use of TNF-antagonists has been associated with rare cases of new onset or exacerbation of clinical 
symptoms and/or radiographic evidence of demyelinating disease, including multiple sclerosis. In 
patients with pre-existing or recent onset of demyelinating disorders, the benefits and risks of 
TNF-antagonist treatment should be carefully considered before initiation of Cimzia therapy. Rare 
cases of neurological disorders, including seizure disorder, neuritis and peripheral neuropathy, have 
been reported in patients treated with Cimzia. 
 
Hypersensitivity 
Severe hypersensitivity reactions have been reported rarely following Cimzia administration. Some of 
these reactions occurred after the first administration of Cimzia. If severe reactions occur, 
administration of Cimzia should be discontinued immediately and appropriate therapy instituted.  
 
There are limited data on the use of Cimzia in patients who have experienced a severe hypersensitivity 
reaction towards another TNF-antagonist; in these patients caution is needed. 
  
Latex-sensitivity  
The needle shield inside the removable cap of the CIMZIA pre-filled pen contains a derivative of 
natural rubber latex (see section 6.5). Contact with natural rubber latex may cause severe allergic 
reactions in individuals sensitive to latex. No antigenic latex protein has to date been detected in the 
removable needle cap of the Cimzia pre-filled pen. Nevertheless, a potential risk of hypersensitivity 
reactions cannot be completely excluded in latex-sensitive individuals. 
 
Immunosuppression 
Since tumour necrosis factor (TNF) mediates inflammation and modulates cellular immune responses, 
the possibility exists for TNF-antagonists, including Cimzia, to cause immunosupression, affecting 
host defences against infections and malignancies. 
 
Autoimmunity 
Treatment with Cimzia may result in the formation of antinuclear antibodies (ANA) and, 
uncommonly, in the development of a lupus-like syndrome (see section 4.8). The impact of long-term 
treatment with Cimzia on the development of autoimmune diseases is unknown. If a patient develops 
symptoms suggestive of a lupus-like syndrome following treatment with Cimzia, treatment must be 
discontinued. Cimzia has not been studied specifically in a lupus population (see section 4.8). 
 
Vaccinations 
Patients treated with Cimzia may receive vaccinations, except for live vaccines. No data are available 
on the response to live vaccinations or the secondary transmission of infection by live vaccines in 
patients receiving Cimzia. Live vaccines should not be administered concurrently with Cimzia. 
 
In a placebo-controlled clinical trial in patients with rheumatoid arthritis, similar antibody response 
between Cimzia and placebo treatment were observed when the pneumococcal polysaccharide vaccine 
and influenza vaccine were administered concurrently with Cimzia. Patients receiving Cimzia and 
concomitant methotrexate had a lower humoral response compared with patients receiving Cimzia 
alone. The clinical significance of this is unknown.  
 



40 

Concomitant use with other biologics 
Severe infections and neutropaenia were reported in clinical trials with concurrent use of anakinra (an 
interleukin-1 antagonist) or abatacept (a CD28 modulator) and another TNF-antagonist, etanercept, 
with no added benefit compared to TNF-antagonist therapy alone. Because of the nature of the adverse 
events seen with the combination of another TNF-antagonist with either abatacept or anakinra therapy, 
similar toxicities may also result from the combination of anakinra or abatacept and other 
TNF-antagonists. Therefore the use of certolizumab pegol in combination with anakinra or abatacept 
is not recommended (see section 4.5). 
 
Surgery 
There is limited safety experience with surgical procedures in patients treated with Cimzia. The 14-day 
half-life of certolizumab pegol should be taken into consideration if a surgical procedure is planned. 
A patient who requires surgery while on Cimzia should be closely monitored for infections, and 
appropriate actions should be taken. 
 
Activated partial thromboplastin time (aPTT) assay 
Interference with certain coagulation assays has been detected in patients treated with Cimzia. Cimzia 
may cause erroneously elevated aPTT assay results in patients without coagulation abnormalities. This 
effect has been observed with the PTT-Lupus Anticoagulant (LA) test and Standard Target Activated 
Partial Thromboplastin time (STA-PTT) Automate tests from Diagnostica Stago, and the HemosIL 
APTT-SP liquid and HemosIL lyophilised silica tests from Instrumentation Laboratories. Other aPTT 
assays may be affected as well. There is no evidence that Cimzia therapy has an effect on coagulation 
in vivo. After patients receive Cimzia, careful attention should be given to interpretation of abnormal 
coagulation results. Interference with thrombin time (TT) and prothrombin time (PT) assays have not 
been observed. 
 
Elderly patients 
In the clinical trials, there was an apparently higher incidence of infections among subjects ≥ 65 years 
of age, compared to younger subjects, although experience is limited. Caution should be exercised 
when treating the elderly patients, and particular attention paid with respect to occurrence of 
infections. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Concomitant treatment with methotrexate, corticosteroids, nonsteroidal anti-inflammatory drugs 
(NSAIDs) and analgesics showed no effect on the pharmacokinetics of certolizumab pegol based on a 
population pharmacokinetics analysis. 
 
The combination of certolizumab pegol and anakinra or abatacept is not recommended (see 
section 4.4). 
 
Co-administration of Cimzia with methotrexate had no significant effect on the pharmacokinetics of 
methotrexate. In study-to-study comparison, the pharmacokinetics of certolizumab pegol appeared 
similar to those observed previously in healthy subjects. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential  
The use of adequate contraception should be considered for women of childbearing potential. For 
women planning pregnancy, continued contraception may be considered for 5 months after the last 
Cimzia dose due to its elimination rate (see section 5.2), but the need for treatment of the woman 
should also be taken into account (see below). 
 
Pregnancy 
Data from more than 500 prospectively collected pregnancies exposed to Cimzia with known 
pregnancy outcomes, including more than 400 pregnancies exposed during the first trimester, does not 
indicate a malformative effect of Cimzia. However, the available clinical experience is too limited to, 



41 

with a reasonable certainty, conclude that there is no increased risk associated with Cimzia 
administration during pregnancy. 
 
Animal studies using a rodent anti-rat TNFα did not reveal evidence of impaired fertility or harm to 
the foetus. However, these are insufficient with respect to human reproductive toxicity (see 
section 5.3). Due to its inhibition of TNFα, Cimzia administered during pregnancy could affect normal 
immune response in the newborn.  
 
Cimzia should only be used during pregnancy if clinically needed. 
 
Non-clinical studies suggest low or negligible level of placental transfer of a homologue Fab-fragment 
of certolizumab pegol (no Fc region) (see section 5.3). 
 
In a clinical study 16 women were treated with certolizumab pegol (200 mg every 2 weeks or 400 mg 
every 4 weeks) during pregnancy. Certolizumab pegol plasma concentrations measured in 14 infants at 
birth were Below the Limit of Quantification (BLQ) in 13 samples; one was 0.042 µg/ml with an 
infant/mother plasma ratio at birth of 0.09%. At Week 4 and Week 8, all infant concentrations were 
BLQ. The clinical significance of low levels certolizumab pegol for infants is unknown. It is 
recommended to wait a minimum of 5 months following the mother’s last Cimzia administration 
during pregnancy before administration of live or live-attenuated vaccines (e.g. BCG vaccine), unless 
the benefit of the vaccination clearly outweighs the theoretical risk of administration of live or live-
attenuated vaccines to the infants. 
 
Breastfeeding 
In a clinical study in 17 lactating women treated with Cimzia, minimal transfer of certolizumab pegol 
from plasma to breast milk was observed. The percentage of the maternal certolizumab pegol dose 
reaching an infant during a 24 hour period was estimated to 0.04% to 0.30 %. In addition, since 
certolizumab pegol is a protein that is degraded in the gastrointestinal tract after oral administration, 
the absolute bioavailability is expected to be very low in a breastfed infant. 
 
Consequently, Cimzia can be used during breastfeeding. 
 
Fertility 
Effects on sperm motility measures and a trend of reduced sperm count in male rodents have been 
observed with no apparent effect on fertility (see section 5.3).  
 
In a clinical trial to assess the effect of certolizumab pegol on semen quality parameters, 20 healthy 
male subjects were randomized to receive a single subcutaneous dose of 400 mg of certolizumab pegol 
or placebo. During the 14-week follow-up, no treatment effects of certolizumab pegol were seen on 
semen quality parameters compared to placebo. 
 
4.7 Effects on ability to drive and use machines 
 
Cimzia may have a minor influence on the ability to drive and use machines. Dizziness (including 
vertigo, vision disorder and fatigue) may occur following administration of Cimzia (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Rheumatoid arthritis 
Cimzia was studied in 4,049 patients with rheumatoid arthritis in controlled and open label trials for 
up to 92 months.  
 
In the placebo-controlled studies, patients receiving Cimzia had an approximately 4 times greater 
duration of exposure compared with the placebo group. This difference in exposure is primarily due to 



42 

patients on placebo being more likely to withdraw early. In addition, Studies RA-I and RA-II had a 
mandatory withdrawal for non-responders at Week 16, the majority of whom were on placebo. 
 
The proportion of patients who discontinued treatment due to adverse events during the controlled 
trials was 4.4% for patients treated with Cimzia and 2.7% for patients treated with placebo. 
 
The most common adverse reactions belonged to the system organ classes Infections and infestations, 
reported in 14.4% of patients on Cimzia and 8.0% of patients on placebo, General disorders and 
administration site conditions, reported in 8.8% of patients on Cimzia and 7.4% of patients on placebo, 
and Skin and subcutaneous tissue disorders, reported in 7.0% of patients on Cimzia and 2.4% of 
patients on placebo. 
 
Axial spondyloarthritis 
Cimzia was initially studied in 325 patients with active axial spondyloarthritis (including ankylosing 
spondylitis and non-radiopraphic axial spondyloarthritis) in the AS001 clinical study for up to 4 years, 
which includes a 24-week placebo-controlled phase followed by a 24-week dose-blind period and 
a 156-week open-label treatment period. Cimzia was subsequently studied in 317 patients with non-
radiographic axial spondyloarthritis in a placebo-controlled study for 52 weeks (AS0006). Cimzia was 
also studied in patients with axial spondyloarthritis (including ankylosing spondylitis and non-
radiographic axial spondyloarthritis) in a clinical study for up to 96 weeks, which included a 48-week 
open-label run-in phase (N=736) followed by a 48-week placebo-controlled phase (N=313) for 
patients in sustained remission (C-OPTIMISE). In all 3 studies, the safety profile for these patients 
was consistent with the safety profile in rheumatoid arthritis and previous experience with Cimzia. 
 
Psoriatic arthritis  
Cimzia was studied in 409 patients with psoriatic arthritis in the PsA001 clinical study for up 
to 4 years which includes a 24-week placebo-controlled phase followed by a 24-week dose-blind 
period and a 168-week open-label treatment period. The safety profile for psoriatic arthritis patients 
treated with Cimzia was consistent with the safety profile in rheumatoid arthritis and previous 
experience with Cimzia. 
 
Plaque psoriasis 
Cimzia was studied in 1112 patients with psoriasis in controlled and open-label studies for up to 3 
years. In the Phase III program, the initial and maintenance periods were followed by a 96-week open-
label treatment period (see section 5.1). The long-term safety profile of Cimzia 400 mg every 2 weeks 
and Cimzia 200 mg every 2 weeks was generally similar and consistent with previous experience with 
Cimzia. 
 
During controlled clinical trials through Week 16, the proportion of patients with serious adverse 
events was 3.5% for Cimzia and 3.7% for placebo.  
The proportion of patients who discontinued treatment due to adverse events in the controlled clinical 
studies was 1.5% for patients treated with Cimzia and 1.4% for patients treated with placebo.  
 
The most common adverse reactions reported through Week 16 belonged to the system organ classes 
Infections and infestations, reported in 6.1% of patients on Cimzia and 7% of patients on placebo, 
General disorders and administration site conditions, reported in 4.1% of patients on Cimzia and 2.3% 
of patients on placebo, and Skin and subcutaneous tissue disorders, reported in 3.5% of patients on 
Cimzia and 2.8% of patients on placebo. 
 
Tabulated list of adverse reactions 
Adverse reactions reactions based primarily on experience from the placebo-controlled clinical trials 
and postmarketing cases at least possibly related to Cimzia are listed in Table 1 below, according to 
frequency and system organ class. Frequency categories are defined as follows: Very common 
(≥ 1/10); Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1000 to < 1/100); Rare 
(≥ 1/10,000 to < 1/1000); Very rare (< 1/10,000), not known (cannot be estimated from the available 
data). Within each frequency grouping, undesirable effects are presented in order of decreasing 
seriousness. 



43 

 
Table 1 Adverse reactions in clinical trials and postmarketing 

System Organ Class  Frequency Adverse reactions  
Infections and 
infestations 

Common bacterial infections (including abscess), viral infections 
(including herpes zoster, papillomavirus, influenza) 

Uncommon sepsis (including multi-organ failure, septic shock), 
tuberculosis (including miliary, disseminated and 
extrapulmonary disease), fungal infections (includes 
opportunistic)  

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

Uncommon blood and lymphatic system malignancies (including 
lymphoma and leukaemia), solid organ tumours, non-
melanoma skin cancers, pre-cancerous lesions (including 
oral leukoplakia, melanocytic nevus), benign tumours 
and cysts (including skin papilloma) 

Rare gastrointestinal tumours, melanoma  
Not known Merkel cell carcinoma*, Kaposi’s sarcoma 

Blood and the lymphatic 
system disorders 

Common eosinophilic disorders, leukopaenia (including 
neutropaenia, lymphopaenia) 

Uncommon anaemia, lymphadenopathy, thrombocytopaenia, 
thrombocytosis 

Rare pancytopaenia, splenomegaly, erythrocytosis, white 
blood cell morphology abnormal 

Immune system disorders Uncommon vasculitides, lupus erythematosus, drug hypersensitivity 
(including anaphylactic shock), allergic disorders, 
auto-antibody positive 

Rare angioneurotic oedema, sarcoidosis, serum sickness, 
panniculitis (including erythema nodosum), worsening of 
symptoms of dermatomyositis** 

Endocrine disorders Rare thyroid disorders 
Metabolism and nutrition 
disorders 

Uncommon electrolyte imbalance, dyslipidaemia, appetite disorders, 
weight change 

Rare haemosiderosis 
Psychiatric disorders Uncommon anxiety and mood disorders (including associated 

symptoms) 
Rare suicide attempt, delirium, mental impairment 

Nervous system disorders Common headaches (including migraine), sensory abnormalities 
Uncommon peripheral neuropathies, dizziness, tremor 
Rare seizure, cranial nerve inflammation, impaired 

coordination or balance 
Not known multiple sclerosis*, Guillain-Barré syndrome* 

Eye disorders Uncommon visual disorder (including decreased vision), eye and 
eyelid inflammation, lacrimation disorder 

Ear and labyrinth 
disorders 

Uncommon tinnitus, vertigo 

Cardiac disorders Uncommon cardiomyopathies (including heart failure), ischaemic 
coronary artery disorders, arrhythmias (including atrial 
fibrillation), palpitations 

Rare pericarditis, atrioventricular block 



44 

System Organ Class  Frequency Adverse reactions  
Vascular disorders Common hypertension 

Uncommon haemorrhage or bleeding (any site), hypercoagulation 
(including thrombophlebitis, pulmonary embolism), 
syncope, oedema (including peripheral, facial), 
ecchymoses (including haematoma, petechiae) 

Rare cerebrovascular accident, arteriosclerosis, Raynaud’s 
phenomenon, livedo reticularis, telangiectasia 

Respiratory, thoracic and 
mediastinal disorders 

Uncommon asthma and related symptoms, pleural effusion and 
symptoms, respiratory tract congestion and 
inflammation, cough 

Rare interstitial lung disease, pneumonitis 
Gastrointestinal disorders Common nausea 

Uncommon ascites, gastrointestinal ulceration and perforation, 
gastrointestinal tract inflammation (any site), stomatitis, 
dyspepsia, abdominal distension, oropharyngeal dryness 

Rare odynophagia, hypermotility 
Hepatobiliary disorders Common hepatitis (including hepatic enzyme increased) 

Uncommon hepatopathy (including cirrhosis), cholestasis, blood 
bilirubin increased 

Rare cholelithiasis 
Skin and subcutaneous 
tissue disorders 

Common rash 
Uncommon alopecia, new onset or worsening of psoriasis (including 

palmoplantar pustular psoriasis) and related conditions, 
dermatitis and eczema, sweat gland disorder, skin ulcer, 
photosensitivity, acne, skin discolouration, dry skin, nail 
and nail bed disorders 

Rare skin exfoliation and desquamation, bullous conditions, 
hair texture disorder, Stevens-Johnson syndrome**, 
erythema multiforme**, lichenoid reactions 

Musculoskeletal, 
connective tissue and 
bone disorders 

Uncommon muscle disorders, blood creatine phosphokinase 
increased 

Renal and urinary 
disorders 

Uncommon renal impairment, blood in urine, bladder and urethral 
symptoms  

Rare nephropathy (including nephritis) 
Reproductive system and 
breast disorders 

Uncommon menstrual cycle and uterine bleeding disorders (including 
amenorrhea), breast disorders  

Rare sexual dysfunction  
General disorders and 
administration site 
conditions 

Common pyrexia, pain (any site), asthaenia, pruritus (any site), 
injection site reactions 

Uncommon chills, influenza-like illness, altered temperature 
perception, night sweats, flushing 

Rare fistula (any site) 
Investigations Uncommon blood alkaline phosphatase increased, coagulation time 

prolonged 
Rare blood uric acid increased 

Injury, poisoning and 
procedural complications 

Uncommon skin injuries, impaired healing 

*These events have been related to the class of TNF-antagonists, but incidence with certolizumab 
pegol is not known. 
**These events have been related to the class of TNF-antagonists. 
 
The additional following adverse reactions have been observed uncommonly with Cimzia in other 
indications: gastrointestinal stenosis and obstructions, general physical health deterioration, abortion 
spontaneous and azoospermia. 



45 

 
Description of selected adverse reactions 
 
Infections 
The incidence rate of new cases of infections in placebo-controlled clinical trials in rheumatoid 
arthritis was 1.03 per patient-year for all Cimzia-treated patients and 0.92 per patient-year for placebo-
treated patients. The infections consisted primarily of upper respiratory tract infections, urinary tract 
infections, and lower respiratory tract infections and herpes viral infections (see sections 4.3 and 4.4). 
 
In the placebo-controlled clinical trials in rheumatoid arthritis, there were more new cases of serious 
infection in the Cimzia treatment groups (0.07 per patient-year; all doses), compared with placebo 
(0.02 per patient-year). The most frequent serious infections included pneumonia, tuberculosis 
infections. Serious infections also included invasive opportunistic infections (e.g. pneumocystosis, 
fungal oesophagitis, nocardiosis and herpes zoster disseminated). There is no evidence of an increased 
risk of infections with continued exposure over time (see section 4.4). 
 
The incidence rate of new cases of infections in placebo-controlled clinical trials in psoriasis 
was 1.37 per patient-year for all Cimzia-treated patients and 1.59 per patient-year for placebo-treated 
patients. The infections consisted primarily of upper respiratory tract infections and viral infections 
(including herpes infections). The incidence of serious infections was 0.02 per patient-year in Cimzia 
treated patients. No serious infections were reported in the placebo-treated patients. There is no 
evidence of an increased risk of infections with continued exposure over time. 
 
Malignancies and lymphoproliferative disorders 
Excluding non-melanoma of the skin, 121 malignancies including 5 cases of lymphoma were observed 
in the Cimzia RA clinical trials in which a total of 4,049 patients were treated, 
representing 9,277 patient-years. Cases of lymphoma occurred at an incidence rate 
of 0.05 per 100 patient-years and melanoma at an incidence rate of 0.08 per 100 patient-years with 
Cimzia in rheumatoid arthritis clinical trials (see section 4.4). One case of lymphoma was also 
observed in the Phase III psoriatic arthritis clinical trial. 
 
Excluding non-melanoma skin cancer, 11 malignancies including 1 case of lymphoma were observed 
in the Cimzia psoriasis clinical trials in which a total of 1112 patients were treated, representing 2300 
patient-years. 
 
Autoimmunity 
In the rheumatoid arthritis pivotal studies, for subjects who were ANA negative at baseline, 16.7% of 
those treated with Cimzia developed positive ANA titers, compared with 12.0% of subjects in the 
placebo group. For subjects who were anti-dsDNA antibody negative at baseline, 2.2% of those treated 
with Cimzia developed positive anti-dsDNA antibody titers, compared with 1.0% of subjects in the 
placebo group. In both placebo-controlled and open-label follow-up clinical trials for rheumatoid 
arthritis, cases of lupus-like syndrome were reported uncommonly. There have been rare reports of 
other immune-mediated conditions; the causal relationship to Cimzia is not known. The impact of 
long-term treatment with Cimzia on the development of autoimmune diseases is unknown. 
 
Injection site reactions 
In the placebo-controlled rheumatoid arthritis clinical trials, 5.8% of patients treated with Cimzia 
developed injection site reactions such as erythema, itching, haematoma, pain, swelling or bruising, 
compared to 4.8% of patients receiving placebo. Injection site pain was observed in 1.5% of patients 
treated with Cimzia with no cases leading to withdrawal. 
 
Creatine phosphokinase elevations 
The frequency of creatine phosphokinase (CPK) elevations was generally higher in patients with 
axSpA as compared to the RA population. The frequency was increased both in patients treated with 
placebo (2.8% vs 0.4% in axSpA and RA populations, respectively) as well as in patients treated with 
Cimzia (4.7% vs 0.8% in axSpA and RA populations, respectively). The CPK elevations in the axSpA 



46 

study were mostly mild to moderate, transient in nature and of unknown clinical significance with no 
cases leading to withdrawal. 
 
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. Multiple doses of up to 800 mg 
subcutaneously and 20 mg/kg intravenously have been administered. In cases of overdose, it is 
recommended that patients are monitored closely for any adverse reactions or effect, and appropriate 
symptomatic treatment initiated immediately. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: immunosuppressants, tumour necrosis factor alpha (TNFα) inhibitors, 
ATC code: L04AB05 
 
Mechanism of action 
 
Cimzia has a high affinity for human TNFα and binds with a dissociation constant (KD) of 90 pM. 
TNFα is a key pro-inflammatory cytokine with a central role in inflammatory processes. Cimzia 
selectively neutralises TNFα (IC90 of 4 ng/ml for inhibition of human TNFα in the in vitro 
L929 murine fibrosarcoma cytotoxicity assay) but does not neutralise lymphotoxin α (TNFβ).  
 
Cimzia was shown to neutralise membrane associated and soluble human TNFα in a dose-dependent 
manner. Incubation of monocytes with Cimzia resulted in a dose-dependent inhibition of 
lipopolysaccharide (LPS)-induced TNFα and IL1β production in human monocytes. 
 
Cimzia does not contain a fragment crystallisable (Fc) region, which is normally present in a complete 
antibody, and therefore does not fix complement or cause antibody-dependent cell-mediated 
cytotoxicity in vitro. It does not induce apoptosis in vitro in human peripheral blood-derived 
monocytes or lymphocytes, or neutrophil degranulation. 
 
Clinical efficacy 
 
Rheumatoid arthritis 
The efficacy and safety of Cimzia have been assessed in 2 randomised, placebo-controlled, double-
blind clinical trials in patients ≥ 18 years of age with active rheumatoid arthritis diagnosed according 
to American College of Rheumatology (ACR) criteria, RA-I (RAPID 1) and RA-II (RAPID 2). 
Patients had ≥ 9 swollen and tender joints each and had active RA for at least 6 months prior to 
baseline. Cimzia was administered subcutaneously in combination with oral MTX for a minimum 
of 6 months with stable doses of at least 10 mg weekly for 2 months in both trials. There is no 
experience with Cimzia in combination with DMARDs other than MTX. 
 
The efficacy and safety of Cimzia was assessed in DMARD-naïve adult patients with active RA in a 
randomized, placebo-controlled, double-blind clinical trial (C-EARLY). In the C-EARLY trial patients 
were ≥ 18 years of age and had ≥ 4 swollen and tender joints each and must have been diagnosed with 
moderate to severe active and progressive RA within 1 year (as defined by the 2010 ACR/European 
League Against Rheumatism (EULAR) classification criteria). Patients had a mean time since 
diagnosis at baseline of 2.9 months and were DMARD naïve (including MTX). For both the Cimzia 



47 

and placebo arms, MTX was initiated as of Week 0 (10 mg/week), titrated up to maximum tolerated 
dose by Week 8 (min 15 mg/week, max 25 mg/week allowed), and maintained throughout the study 
(average dose of MTX after Week 8 for placebo and Cimzia was 22.3 mg/week and 21.1 mg/week 
respectively). 
 
Table 2 Clinical trial description 

Study 
number 

Patient 
numbers 

Active dose regimen Study objectives 
 

RA-I 
(52 weeks) 

982 400 mg (0,2,4 weeks) 
with MTX 

200 mg or 400 mg 
every 2 weeks with MTX 

Evaluation for treatment of signs and 
symptoms and inhibition of structural damage.  
Co-primary endpoints: ACR 20 at Week 24 and 

change from baseline in mTSS at Week 52 
RA-II 

(24 weeks) 
619 400 mg (0,2,4 weeks) 

with MTX 
200 mg or 400 mg 
every 2 weeks with 

MTX 

Evaluation for treatment of signs and 
symptoms and inhibition of structural damage. 

Primary endpoint: ACR 20 at Week 24.  

C-EARLY 
(to 52 wee

ks) 

879 400 mg (0,2,4 weeks) 
with MTX 

200 mg every 2 weeks 
with MTX 

Evaluation for treatment of signs and 
symptoms and inhibition of structural damage 

in DMARD naïve patients.  
Primary endpoint: proportion of subjects in 

sustained remission* at Week 52 
mTSS: modified Total Sharp Score 
*Sustained remission at Week 52 is defined as DAS28[ESR] <2.6 at both Week 40 and Week 52. 
 
Signs and symptoms 
The results of clinical trials RA-I and RA-II are shown in Table 3. Statistically significantly greater 
ACR 20 and ACR 50 responses were achieved from Week 1 and Week 2, respectively, in both clinical 
trials compared to placebo. Responses were maintained through Weeks 52 (RA-I) and 24 (RA-II). Of 
the 783 patients initially randomised to active treatment in RA-I, 508 completed 52 weeks of placebo-
controlled treatment and entered the open-label extension study. Of these, 427 completed 2 years of 
open-label follow-up and thus had a total exposure to Cimzia of 148 weeks overall. The observed 
ACR 20 response rate at this timepoint was 91%.The reduction (RA-I) from Baseline in DAS28 (ESR) 
also was significantly greater (p<0.001) at Week 52 (RA-I) and Week 24 (RA-II) compared to placebo 
and maintained through 2 years in the open-label extension trial to RA-I. 
 
Table 3 ACR response in clinical trials RA-I and RA-II 

 Study RA-I 
Methotrexate combination 

(24 and 52 weeks) 

Study RA-II 
Methotrexate combination 

(24 weeks) 
Response Placebo + MTX 

 
N=199 

Cimzia  
200 mg + MTX 
every 2 weeks 

 
N=393 

Placebo + MTX 
 

N=127 

Cimzia  
200 mg + MTX 
every 2 weeks 

 
N=246 

ACR 20     
Week 24 14% 59%** 9% 57%** 
Week 52 13% 53%** N/A N/A 
ACR 50     
Week 24 8% 37%** 3% 33%** 
Week 52 8% 38%** N/A N/A 
ACR 70     
Week 24 3% 21%** 1% 16%* 
Week 52 4% 21%** N/A N/A 



48 

Major 
Clinical 
Responsea. 

1% 13%**   

Cimzia vs. placebo: *p≤0.01, ** p<0.001 
a. Major clinical response is defined as achieving ACR 70 response at every assessment over a 
continuous 6-month period 
Wald p-values are quoted for the comparison of treatments using logistic regression with factors for 
treatment and region. 
Percentage response based upon number of subjects contributing data (n) to that endpoint and time 
point which may differ from N 

 
The C-EARLY trial met its primary and key secondary endpoints. The key results from the study are 
presented in table 4.  
 
Table 4:  C-EARLY trial: percent of patients in sustained remission and sustained low disease 

activity at Week 52 
Response Placebo+MTX 

N= 213 
Cimzia 200 mg + MTX 

N= 655 
Sustained remission* 
(DAS28(ESR) <2.6 at both Week 40 and Week 52) 

15.0 % 28.9%** 

Sustained low disease activity 
(DAS28(ESR) ≤3.2 at both Week 40 and Week 52) 

28.6 % 43.8%** 

*Primary endpoint of C-EARLY trial (to Week 52) 
Full analysis set, non-responder imputation for missing values. 
**Cimzia+MTX vs placebo+MTX: p<0.001 
p value was estimated from a logistic regression model with factors for treatment, region, and time 
since RA diagnosis at Baseline (≤4 months vs >4 months) 

 
Patients in the Cimzia+MTX group had a greater reduction from baseline in DAS 28 (ESR) compared 
with the placebo+MTX group observed as early as Week 2 and continued through 
Week 52 (p<0.001 at each visit). Assessments on remission (DAS28(ESR) <2.6), Low Disease 
Activity (DAS28(ESR) ≤3.2) status, ACR50 and ACR 70 by visit demonstrated that Cimzia+MTX 
treatment led to faster and greater responses than PBO+MTX treatment. These results were maintained 
over 52 weeks of treatment in DMARD-naïve subjects.  
 
Radiographic response 
In RA-I, structural joint damage was assessed radiographically and expressed as change in mTSS and 
its components, the erosion score and joint space narrowing (JSN) score, at Week 52, compared to 
baseline. Cimzia patients demonstrated significantly less radiographic progression than patients 
receiving placebo at Week 24 and Week 52 (see Table 5). In the placebo group, 52% of patients 
experienced no radiographic progression (mTSS ≤ 0.0) at Week 52 compared to 69% in the 
Cimzia 200 mg treatment group. 
 
Table 5 Changes over 12 months in RA-I 

 Placebo + MTX 
N=199 

Mean (SD) 

Cimzia 200 mg + MTX 
N=393 

Mean (SD) 

Cimzia 200 mg + MTX – 
Placebo + MTX 
Mean Difference 

mTSS    
Week 52 2.8 (7.8) 0.4 (5.7) -2.4 
Erosion Score    
Week 52 1.5 (4.3) 0.1 (2.5) -1.4 
JSN Score    
Week 52 1.4 (5.0) 0.4 (4.2) -1.0 
p-values were < 0.001 for both mTSS and erosion score and ≤ 0.01 for JSN score. An ANCOVA 
was fitted to the ranked change from baseline for each measure with region and treatment as factors 
and rank baseline as a covariate. 

 



49 

Of the 783 patients initially randomised to active treatment in RA-I, 508 completed 52 weeks of 
placebo-controlled treatment and entered the open-label extension study. Sustained inhibition of 
progression of structural damage was demonstrated in a subset of 449 of these patients who completed 
at least 2 years of treatment with Cimzia (RA-I and open-label extension study) and had evaluable data 
at the 2-year timepoint. 
 
In C-EARLY, Cimzia+ MTX inhibited the radiographic progression compared to placebo+MTX at 
Week 52 (see Table 6). In the placebo+MTX group, 49.7% of patients experienced no radiographic 
progression (change in mTSS ≤0.5) at Week 52 compared to 70.3% in the Cimzia+MTX group 
(p<0.001). 
 
Table 6 Radiographic change at Week 52 in trial C-EARLY 

 Placebo +MTX 
N= 163 

Mean (SD) 

Cimzia 200 mg + MTX 
N = 528 

Mean (SD) 

Cimzia 200 mg + MTX – 
Placebo +MTX 

Difference* 
mTSS 
Week 52 

1.8 (4.3) 0.2 (3.2)** -0.978 (-1.005, -0.500) 

Erosion score 
Week 52 

1.1 (3.0) 0.1 (2.1)** -0.500 (-0.508, -0.366) 

JSN score 
Week 52 

0.7 (2.3) 0.1 (1.7)** 0.000 (0.000, 0.000) 

Radiographic set with linear extrapolation. 
* Hodges-Lehmann point estimate of shift and 95% asymptotic (Moses) confidence interval. 
**Cimzia+MTX vs placebo+MTX p<0.001. p value was estimated from an ANCOVA model on the 
ranks with treatment, region, time since RA diagnosis at Baseline (≤4 months vs >4 months) as 
factors and Baseline rank as a covariate. 

 
Physical function response and health-related outcomes 
In RA-I and RA-II, Cimzia-treated patients reported significant improvements in physical function as 
assessed by the Health Assessment Questionnaire – Disability Index (HAQ-DI) and in tiredness 
(fatigue) as reported by the Fatigue Assessment Scale (FAS) from Week 1 through to the end of the 
studies compared to placebo. In both clinical trials, Cimzia-treated patients reported significantly 
greater improvements in the SF-36 Physical and Mental Component Summaries and all domain scores. 
Improvements in physical function and HRQoL were maintained through 2 years in the open-label 
extension to RA-I. Cimzia-treated patients reported statistically significant improvements in the Work 
Productivity Survey compared to placebo. 
 
In C-EARLY, Cimzia+MTX-treated patients reported significant improvements at Week 52 compared 
to placebo+MTX in pain as assessed by the Patient Assessment of Arthritis Pain (PAAP) – 48,5 vs 
- 44,0 (least square mean) (p<0.05). 
 
DoseFlex clinical trial 
The efficacy and safety of 2 dose regimens (200 mg every 2 weeks and 400 mg every 4 weeks) of 
Cimzia versus placebo were assessed in an 18-week, open-label, run-in, and 16-week randomised, 
double-blind, placebo-controlled clinical trial in adult patients with active rheumatoid arthritis 
diagnosed according to the ACR criteria who had inadequate response to MTX. 
 
Patients received loading doses of Cimzia 400 mg at weeks 0, 2, and 4 followed by Cimzia 200 mg 
every 2 weeks during the initial open label period. Responders (achieved ACR 20) at week 16 were 
randomised at week 18 to Cimzia 200 mg every 2 weeks, Cimzia 400 mg every 4 weeks, or placebo in 
combination with MTX for an additional 16 weeks (total trial length: 34 weeks). These 3 groups were 
well balanced with regards to clinical response following the active run-in period (ACR 20: 83-84% at 
week 18). 
 
The primary endpoint of the study was the ACR 20 responder rate at week 34. The results at 
week 34 are shown in Table 7. Both Cimzia regimens showed sustained clinical response and were 



50 

statistically significant compared to placebo at week 34. The ACR 20 endpoint was achieved for both 
Cimzia 200 mg every 2 weeks and 400 mg every 4 weeks. 
 
Table 7 ACR response in DoseFlex clinical trial at week 34 

Treatment regimen week 0 to 16 Cimzia 400 mg + MTX at week 0, 2 and 4, followed by 
Cimzia 200 mg + MTX every 2 weeks  

Randomised, double-blind 
treatment regimen 
week 18 to 34 
 

Placebo + MTX 
 
 

N=69 

Cimzia  
200 mg + MTX 
every 2 weeks 

N=70 

Cimzia  
400 mg + MTX 
every 4 weeks 

N=69 
ACR 20 
p-value* 

45% 
N/A 

67% 
0.009 

65% 
0.017 

ACR 50 
p-value* 

30% 
N/A 

50% 
0.020 

52% 
0.010 

ACR 70 
p-value* 

16% 
N/A 

30% 
0.052 

38% 
0.005 

N/A: Not Applicable 
*Wald p-values for Cimzia 200 mg vs. placebo and Cimzia 400 mg vs. placebo comparisons are 
estimated from a logistic regression model with factors for treatment 

 
Axial spondyloarthritis (non-radiographic axial spondyloarthritis and ankylosing spondylitis 
subpopulations) 
AS001 
The efficacy and safety of Cimzia were assessed in one multicenter, randomized, double-blind, 
placebo-controlled trial (AS001) in 325 patients ≥18 years of age with adult-onset active axial 
spondyloarthritis for at least 3 months as defined by the Assessment of Spondyloarthritis International 
Society (ASAS) Classification Criteria for axial spondyloarthritis. The axial spondyloarthritis overall 
population included subpopulations with and without (non-radiographic axial spondyloarthritis [nr-
axSpA]) radiographic evidence for ankylosing spondylitis (AS) (also known as radiographic axial 
spondyloarthritis). Patients had active disease as defined by the Bath Ankylosing Spondylitis Disease 
Activity Index (BASDAI) ≥ 4, spinal pain ≥ 4 on a 0 to 10 Numerical Rating Scale (NRS) and 
increased CRP or current evidence of sacroiliitis on Magnetic Resonance Imaging (MRI). Patients 
must have been intolerant to or had an inadequate response to at least one NSAID. Overall, 16% of 
patients had prior TNF-antagonist exposure. Patients were treated with a loading dose of 
Cimzia 400 mg at Weeks 0, 2 and 4 (for both treatment arms) or placebo followed by either 200 mg of 
Cimzia every 2 weeks or 400 mg of Cimzia every 4 weeks or placebo. 87.7% of patients received 
concomitant NSAIDs. The primary efficacy endpoint was the ASAS20 response rate at Week 12. 
The 24-week double-blind, placebo-controlled treatment period of the study was followed by 
a 24-week dose-blind treatment period, and a 156-week open-label treatment period. The maximum 
duration of the study was 204 weeks. All patients received Cimzia in both the dose-blind and open-
label follow-up periods. A total of 199 subjects (61.2% of randomized subjects) completed the study 
through Week 204.  
 
Key efficacy outcomes 
In AS001 clinical trial, at Week 12 ASAS20 responses were achieved by 58% of patients receiving 
Cimzia 200 mg every 2 weeks and 64% of patients receiving Cimzia 400 mg every 4 weeks as 
compared to 38% of patients receiving placebo (p<0.01). In the overall population, the percentage of 
ASAS20 responders was clinically relevant and significantly higher for the Cimzia 200 mg 
every 2 weeks and Cimzia 400 mg every 4 weeks treatment groups compared to placebo group at 
every visit from Week 1 through Week 24 (p≤0.001 at each visit). At Weeks 12 and 24, the percentage 
of subjects with an ASAS40 response was greater in the Cimzia-treated groups compared to placebo.  
Similar results were achieved in both the ankylosing spondylitis and non-radiographic axial 
spondyloarthritis subpopulations. In women, ASAS20 responses were not statistically significantly 
different from placebo until after the Week 12 time point. 
 



51 

Improvements in ASAS5/6, Partial Remission and BASDAI-50 were statistically signficant at 
Week 12 and Week 24 and were sustained up to Week 48 in the overall popualtion as well as in the 
subpopulations. Key efficacy outcomes from the AS001 clinical trial are shown in Table -8.  
 
Among patients remaining in the study, improvements in all afore-mentioned key efficacy outcomes 
were maintained through Week 204 in the overall population as well as in the subpopulations. 
 
Table 8 Key efficacy outcomes in AS001 clinical trial (percent of patients) 

 
 

Parameters 

Ankylosing spondylitis Non-radiographic 
axial 

spondyloarthritits 

 Axial 
spondyloarthritis 

Overall Population 
 Placebo 

N=57 
Cimzia 

all dosing 
regimens(a) 

N=121 

Placebo 
N=50 

Cimzia all 
dosing 

regimens(a) 
N=97 

Placebo 
N=107 

 

Cimzia all 
dosing 

regimens(a) 
N=218 

ASAS20(b,c) 
Week 12 
Week 24 

 
37% 
33% 

 
60%* 

69%** 

 
40% 
24% 

 
61%* 

68%** 

 
38% 
29% 

 
61%** 
68%** 

ASAS40(c,d) 
Week 12 
Week 24 

 
19% 
16% 

 
45%** 
53%** 

 
16% 
14% 

 
47%** 
51%** 

 
18% 
15% 

 
46%** 
52%** 

ASAS 5/6(c,d) 
Week 12 
Week 24 

 
9% 
5% 

 
42%** 
40%** 

 
8% 
4% 

 
44%** 
45%** 

 
8% 
5% 

 
43%** 
42%** 

Partial remission(c,d) 
Week 12 
Week 24 

 
2% 
7% 

 
20%** 
28%** 

 
6% 
10% 

 
29%** 
33%** 

 
4% 
9% 

 
24%** 
30%** 

BASDAI 50(c,d) 
Week 12 
Week 24 

 
11% 
16% 

 
41%** 
49%** 

 
16% 
20% 

 
49%** 
57%** 

 
13% 
18% 

 
45%** 
52%** 

(a) Cimzia all dosing regimen = data from Cimzia 200 mg administered every 2 weeks preceded by a 
loading dose of 400 mg at Weeks 0, 2 and 4 plus Cimzia 400 mg administered every 4 weeks preceded 
by a loading dose of 400 mg at Weeks 0, 2 and 4 
(b) Results are from the randomized set 
(c) Wald p-values are quoted for the comparison of treatments using logistic regression with factors for 
treatment and region.  
(d) Full Analysis Set  
NA = not available 
*p≤0.05, Cimzia vs placebo 
**p<0.001, Cimzia vs placebo 

 
Spinal mobility 
Spinal mobility was assessed in the double-blind, placebo-controlled period by using BASMI at 
several time points including Baseline, Week 12 and Week 24. Clinically meaningful and statistically 
significant differences in Cimzia-treated patients compared with placebo-treated patients were 
demonstrated at each post-baseline visit. The difference from placebo tended to be greater in nr-axSpA 
than in the AS subpopulation which may be due to less chronic structural damage in nr-axSpA 
patients. 
The improvement in BASMI linear score achieved at Week 24 was maintained through Week 204 for 
patients who remained in the study. 
 
Physical function response and health-related outcomes  
In the AS001 clinical trial, Cimzia-treated patients reported significant improvements in physical 
function as assessed by the BASFI and in pain as assessed by the Total and Nocturnal Back Pain NRS 
scales as compared to placebo. Cimzia-treated patients reported significant improvements in tiredness 
(fatigue) as reported by the BASDAI-fatigue item and in health-related quality of life as measured by 



52 

the ankylosing spondylitis QoL (ASQoL) and the SF-36 Physical and Mental Component Summaries 
and all domain scores as compared to placebo. Cimzia-treated patients reported significant 
improvements in axial spondyloarthritis-related productivity at work and within household, as reported 
by the Work Productivity Survey as compared to placebo. For patients remaining in the study, 
improvements in all afore-mentioned outcomes were largely maintained through Week 204. 
 
Inhibition of inflammation in Magnetic Resonance Imaging (MRI) 
In an imaging sub-study including 153 patients, signs of inflammation were assessed by MRI at 
week 12 and expressed as change from baseline in SPARCC (Spondyloarthritis Research Consortium 
of Canada) score for sacroiliac joints and ASspiMRI-a score in the Berlin modifications for the spine. 
At week 12 significant inhibition of inflammatory signs in both sacroiliac joints and the spine was 
observed in the Cimzia-treated patients (all dose group), in the overall axial spondyloarthritis 
population as well as in the sub-populations of ankylosing spondylitis and non-radiographic axial 
spondyloarthritis. Among patients remaining in the study, who had both baseline values and 
week 204 values, inhibition of inflammatory signs in both the sacroiliac joints (n=72) and spine (n=82) 
was largely maintained through Week 204 in the overall axial spondyloarthritis population as well as 
in both the AS and the nr-axSpA subpopulations. 
 

C-OPTIMISE 

The efficacy and safety of dose reduction and treatment withdrawal in patients in sustained remission 
were assessed in adult patients (18-45 years of age) with early active axSpA (symptom duration of less 
than 5 years), an ASDAS score ≥2.1 (and similar disease inclusion criteria as in the AS001 study), and 
who had inadequate response to at least 2 NSAIDs or an intolerance to or contraindication for 
NSAIDs. Patients included both the AS and nr-axSpA subpopulations of axSpA, and were enrolled 
into an open-label run-in 48-Week period (Part A) during which they all received 3 loading doses of 
Cimzia 400 mg at Weeks 0, 2, and 4 followed by Cimzia 200 mg every 2 weeks from Week 6 to Week 
46.   

Patients who achieved sustained remission (defined as having inactive disease [ASDAS<1.3] over a 
period of at least 12 weeks) and remained in remission at week 48, were randomized into Part B and 
received either Cimzia 200 mg every 2 weeks (N=104), Cimzia 200 mg every 4 weeks (dose 
reduction, N=105), or placebo (treatment withdrawal, N=104) for 48 Weeks.  

The primary efficacy variable was the percentage of patients who did not experience a flare during 
Part B. 

Patients who experienced a flare in Part B, ie, had an ASDAS ≥2.1 at 2 consecutive visits or 
ASDAS >3.5 at any visit during Part B, received escape treatment of Cimzia 200 mg every 2 weeks 
for at least 12 weeks (with a loading dose of Cimzia 400 mg at Week 0, 2 and 4 in placebo-treated 
patients).  

Clinical response 

The percentage of patients who achieved sustained remission at Week 48 in Part A was 43.9% for the 
overall axSpA population, and was similar in the nr-axSpA (45.3%) and AS (42.8%) subpopulations. 

Among the patients who were randomized in Part B (N=313), a statistically significant (p <0.001, NRI) 
greater proportion of patients did not experience a flare when continuing treatment with Cimzia 200 
mg every 2 weeks (83.7%) or Cimzia 200 mg every 4 weeks (79.0%) compared with treatment 
withdrawal (20.2%).   

The difference in time to flare between the treatment withdrawal group and either of the Cimzia 
treatment groups, was statistically significant (p<0.001 for each comparison) and clinically 
meaningful. In the placebo group, flares started approximately 8 weeks after CIMZIA was withdrawn, 
with the majority of flares occurring within 24 weeks of treatment withdrawal (Figure 1).  



53 

Figure 1   Kaplan-Meier curve of time to flare 

 
Non responder imputation (NRI) was used; Results are for the Randomized Set 
Note: Time to flare was defined as the time from the date of randomization to the date of the flare. For study participants who did not have a  
flare, the time to flare was censored at the date of Week 96 Visit. 
The Kaplan-Meier plot was truncated to 97 weeks when <5% of participants were still remaining in the study. 
 

Results for Part B are presented in Table 9. 

 
Table 9   Maintenance of clinical response in Part B at Week 96  

Endpoints 

Placebo 
(treatment 

withdrawal) 
N=104 

CIMZIA 200 mg 
every 2 weeks 

N=104 

CIMZIA 200 mg  

every 4 weeks 
N=105 

ASDAS-MI, n (%)1  
Part B Baseline (Week 48) 84 (80.8) 90 (86.5) 89 (84.8) 

Week 96 11 (10.6) 70 (67.3)* 61 (58.1)* 

ASAS40, n (%)1  

Part B Baseline (Week 48) 101 (97.1) 103 (99.0) 101 (96.2) 

Week 96 22 (21.2) 88 (84.6)* 77 (73.3)* 

BASDAI change from Part B 
baseline (Week 48), LS mean (SE)2  

Week 96 3.02 (0.226) 0.56 (0.176)* 0.78 (0.176)* 

ASDAS change from Part B 
baseline (Week 48), LS mean (SE)2  

Week 96 1.66 (0.110) 0.24 (0.077)* 0.45 (0.077)* 
1 Non responder imputation (NRI) was used; Results are for the Randomized Set 
2 mixed model with repeated measures (MMRM) was used; Results are for the Randomized Set 
ASDAS-MI = Ankylosing Spondylitis Disease Activity Score-Major Improvement; ASAS: Assessment of Sponyloarthritis international 
Society; ASAS40= ASAS40% response criteria; SE = Standard error;  
Note: ASDAS major improvement is defined as a reduction from Baseline ≥2.0.  
Note: Part A Baseline was used as a reference to define ASDAS clinical improvement variables and ASAS variables  
* Nominal p<0.001, CIMZIA vs. placebo 

 



54 

Inhibition of inflammation in Magnetic Resonance imaging (MRI) 
In Part B, signs of inflammation were assessed by MRI at Week 48 and at Week 96 and expressed as 
change from baseline in SIJ SPARCC and ASspiMRI-a score in the Berlin modifications. Patients who 
were in sustained remission at Week 48 had no or very low inflammation, and no meaningful increase 
in inflammation was observed at Week 96 irrespective of their treatment group. 
 
Retreatment in patients that experience a flare 
In Part B, 70% (73/104) placebo-treated patients, 14% (15/105) patients treated with Cimzia 200 mg 
every 4 weeks and 6.7% (7/104) patients treated with Cimzia 200 mg every 2 weeks experienced a flare 
and were subsequently treated with Cimzia 200 mg every 2 weeks.  
Among the 15 patients who flared in the group allocated to Cimzia 200 mg every 4 weeks, all patients 
completed 12 weeks of rescue therapy with Cimzia and had available ASDAS data, out of which 12 
(80%) had ASDAS Low or Inactive disease (i.e. all ASDAS <2.1) after 12 weeks of restarting the open-
label treatment. 
Among the 73 patients who flared in the group allocated to treatment withdrawal, 71 patients completed 
12 weeks of rescue therapy with Cimzia and had available ASDAS data, out of which 64 (90%) had 
ASDAS Low or Inactive disease (i.e. all ASDAS < 2.1) after 12 weeks of restarting the open-label 
treatment.  
Based on the results from C-OPTIMISE, a dose reduction in patients in sustained remission after one 
year of treatment with Cimzia may be considered (see section 4.2). Withdrawal of Cimzia treatment is 
associated with a high risk of flare. 
 
Non-radiographic axial spondyloarthritis (nr-axSpA) 
The efficacy and safety of Cimzia were assessed in a 52 weeks multicenter, randomized, double-blind, 
placebo-controlled study (AS0006) in 317 patients ≥18 years of age with adult-onset axial 
spondyloarthritis and back pain for at least 12 months. Patients had to fulfil ASAS criteria for nr- 
axSpA (not including family history and good response to NSAIDs), and have had objective signs of 
inflammation indicated by C-reactive protein (CRP) levels above the upper limit of normal and/or 
sacroiliitis on magnetic resonance imaging (MRI), indicative of inflammatory disease [positive CRP 
(> ULN) and/or positive MRI], but without definitive radiographic evidence of structural damage on 
sacroiliac joints. Patients had active disease as defined by the BASDAI ≥4, and spinal pain ≥4 on 
a 0 to 10 NRS. Patients must have been intolerant to or had an inadequate response to at least two 
NSAIDs. Patients were treated with placebo or a loading dose of Cimzia 400 mg at 
Weeks 0, 2 and 4 followed by 200 mg of Cimzia every 2 weeks. Utilization and dose adjustment of 
standard of care medication (SC) (e.g., NSAIDs, DMARDs, corticosteroids, analgesics) were 
permitted at any time. The primary efficacy variable was the Ankylosing Spondylitis Disease Activity 
Score major improvement (ASDAS-MI) response at Week 52. ASDAS-MI response was defined as an 
ASDAS reduction (improvement) ≥ 2.0 relative to baseline or as reaching the lowest possible score. 
ASAS 40 was a secondary endpoint.  
At baseline, 37 % and 41% of patients had high disease activity (ASDAS ≥2.1, ≤3.5) and 62% 
and 58% of patient had very high disease activity (ASDAS >3.5) in the CIMZIA group and placebo 
group respectively.  
 
Clinical response 
Study AS0006, performed in subjects without radiographic signs of inflammation in the SI joints, 
confirmed the effect previously demonstrated in this subgroup in the AS001 study.  
At Week 52, a statistically significant greater proportion of patients treated with Cimzia achieved 
ASDAS-MI response compared to patients treated with placebo. Cimzia-treated patients also had 
improvements compared to placebo in multiple components of axial spondyloarthritis disease activity, 
including CRP. At both Week 12 and 52, ASAS 40 responses were significantly greater than placebo. 
Key results are presented in Table 10. 
 



55 

Table 10: ASDAS-MI and ASAS 40 responses in AS0006 (percent of patients) 
 

Parameters PlaceboN= 158 Cimzia
a 200 mg every 2 weeks 

N= 159 
ASDAS-MI  
Week 52 

 
7% 
 

 
47%* 

ASAS 40 
Week 12 
 
Week 52 

 
11% 
 
16% 

 
48%* 
 
57%* 

a Cimzia administered every 2 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4 
* p<0.001 
All percents reflect the proportion of patients who responded in the full analysis set.  
 
At Week 52, the percentage of patients achieving ASDAS inactive disease (ASDAS < 1.3) was 36.4 % 
for the Cimzia group compared to 11.8 % for the placebo group. 

 
At Week 52, patients treated with Cimzia showed a clinical meaningful improvement in the MASES 
compared to placebo (LS mean change from baseline -2.4 ; -0.2 respectively).  
 
Psoriatic arthritis 
The efficacy and safety of Cimzia were assessed in a multicentre, randomised, double-blind, placebo 
controlled clinical trial (PsA001) in 409 patients ≥ 18 years of age with adult-onset active psoriatic 
arthritis for at least 6 months as defined by the Classification Criteria for Psoriatic Arthritis 
(CASPAR) criteria. Patients had ≥ 3 swollen and tender joints and increased acute phase reactants. 
Patients also had active psoriatic skin lesions or a documented history of psoriasis and had failed 1 or 
more DMARDs. Previous treatment with one TNF-antagonist was allowed and 20% of patients had 
prior TNF-antagonist exposure. Patients received a loading dose of Cimzia 400 mg at 
Weeks 0, 2 and 4 (for both treatment arms) or placebo followed by either Cimzia 200 mg 
every 2 weeks or 400 mg every 4 weeks or placebo every 2 weeks. Patients receiving concomitant 
NSAIDs and conventional DMARDs were 72.6% and 70.2% respectively. The two primary endpoints 
were the percentage of patients achieving ACR 20 response at Week 12 and change from baseline in 
modified Total Sharp Score (mTSS) at Week 24. Efficacy and safety of Cimzia in patients with PsA 
whose predominant symptoms were sacroiliitis or axial spondyloarthritis have not been separately 
analysed. 
The 24-week double-blind placebo controlled treatment period of the study was followed by 
a 24-week dose-blind treatment period and an 168-week open-label treatment period. The maximum 
duration of the study was 216 weeks. All patients received Cimzia in both the dose-blind and open-
label follow-up periods. A total of 264 subjects (64.5%) completed the study through Week 216. 
 
ACR response 
Cimzia-treated patients had a statistically significant higher ACR 20 response rate at Week 12 and 
Week 24 compared with placebo-treated patients (p<0.001). The percentage of ACR 20 responders 
was clinically relevant for the Cimzia 200 mg every 2 weeks and Cimzia 400 mg every 4 weeks 
treatment groups compared to placebo group at every visit after baseline through Week 24 (nominal 
p≤0.001 at each visit). Cimzia treated patients also had significant improvements in 
ACR 50 and 70 response rates. At week 12 and 24 improvements in parameters of peripheral activity 
characteristic of psoriatic arthritis (e.g. number of swollen joints, number of painful/tender joints, 
dactylitis and enthesitis) were seen in the Cimzia-treated patients (nominal p-value p<0.01).  
 
Key efficacy outcomes from the PsA001 clinical trial are shown in Table11. 
 



56 

Table 11: Key efficacy outcomes in PsA001 clinical trial (percent of patients) 
Response Placebo 

 
N=136 

Cimzia(a)200 mg 
Q2W 
N=138 

Cimzia(b) 400 mg 
Q4W 
N=135 

ACR20 
Week 12 
Week 24 

 
24% 
24% 

 
58%** 
64%** 

 
52%** 
56%** 

ACR50 
Week 12 
Week 24 

 
11% 
13% 

 
36%** 
44%** 

 
33%** 
40%** 

ACR70 
Week 12 
Week 24 

 
3% 
4% 

 
25%** 
28%** 

 
13%* 
24%** 

Response Placebo 
 

N=86 

Cimzia(a)200 mg 
Q2W 
N=90 

Cimzia(b) 400 mg 
Q4W 
N=76 

PASI 75 (c) 
Week 12 
Week 24 
Week 48 

 
14% 
15% 
N/A 

 
47%*** 
62%*** 
67% 

 
47%*** 
61%*** 
62% 

(a) Cimzia administered every 2 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4 
(b) Cimzia administered every 4 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4 
(c) In subjects with at least 3% psoriasis BSA at Baseline 
*p<0.01, Cimzia vs placebo 
**p<0.001, Cimzia vs placebo  
***p<0.001(nominal), Cimzia vs placebo  
Results are from the randomized set.Treatment Difference: Cimzia 200 mg-placebo, Cimzia 400 mg-  
placebo (and corresponding 95% CI and p-value) are estimated using a standard two-sided Wald 
asymptotic standard errors test. Non-responder Imputation (NRI) is used for patients who escaped 
therapy or had missing data. 

 
Among 273 patients initially randomised to Cimzia 200 mg every 2 weeks and Cimzia 400 mg 
every 4 weeks, 237 (86.8%) were still on this treatment at Week 48. Of the 138 patients randomised to 
Cimzia 200 mg every 2 weeks, 92, 68 and 48 had an ACR 20/50/70 response, at Week 48, 
respectively. Of the 135 patients randomised to Cimzia 400 mg every 4 weeks, 89, 62 and 41 patients 
had an ACR 20/50/70 response, respectively.  
Among patients remaining in the study, ACR 20, 50 and 70 response rates were maintained through 
Week 216. This was also the case for the other parameters of peripheral activity (e.g. number of 
swollen joints, number of painful/tender joints, dactylitis and enthesitis). 
 
Radiographic response 
In PsA001 clinical trial, inhibition of progression of structural damage was assessed radiographically 
and expressed as the change in modified total Sharp score (mTSS) and its components, the Erosion 
Score (ES) and Joint Space Narrowing score (JSN) at Week 24, compared to baseline. The mTSS 
Score was modified for psoriatic arthritis by addition of hand distal interphalangeal joints. Cimzia 
treatment inhibited the radiographic progression compared with placebo treatment at Week 24 as 
measured by change from baseline in total mTSS Score (LS mean [±SE] score was 0.28 [±0.07] in the 
placebo group compared with 0.06 [±0.06] in the Cimzia all doses group; p=0.007). Inhibition of 
radiographic progression was maintained with Cimzia treatment up to Week 48 in the subset of 
patients at higher risk of radiographic progression (patients with a Baseline mTSS score of > 6). 
Inhibition of radiographic progression was further maintained up to Week 216 for the patients who 
remained in the study. 
 
Physical function response and health-related outcomes 
In PsA001 clinical trial, Cimzia-treated patients reported significant improvements in physical 
function as assessed by the Health Assessment Questionnaire – Disability Index (HAQ-DI), in pain as 



57 

assessed by the PAAP and in tiredness (fatigue) as reported by the Fatigue Assessment Scale (FAS) as 
compared to placebo. Cimzia-treated patients reported significant improvements in health-related 
quality of life as measured by the psoriatic arthritis QoL (PsAQoL) and the SF-36 Physical and Mental 
Components and in psoriatic arthritis-related productivity at work and within household, as reported 
by the Work Productivity Survey compared to placebo. Improvements in all afore-mentioned 
outcomes were maintained through Week 216. 
 
Plaque psoriasis 
The efficacy and safety of Cimzia were assessed in two placebo-controlled studies (CIMPASI-1 and 
CIMPASI-2) and one placebo- and active-controlled study (CIMPACT) in patients ≥18 years of age 
with moderate to severe chronic plaque psoriasis for at least 6 months. Patients had a Psoriasis Area 
and Severity Index (PASI) score ≥ 12, body surface area (BSA) involvement of ≥ 10%, Physician 
Global Assessment (PGA) of ≥ 3, and were candidates for systemic therapy and/or phototherapy 
and/or chemophototherapy. Patients who were ‘primary’ non-responders on any prior biologic therapy 
(defined as no response within the first 12 weeks of treatment) were excluded from the phase III 
studies (CIMPASI-1, CIMPASI-2 and CIMPACT). The efficacy and safety of Cimzia were evaluated 
versus etanercept in the CIMPACT study. 
 
In studies CIMPASI-1 and CIMPASI-2 the co-primary efficacy endpoints were the proportion of 
patients achieving PASI 75 and PGA “clear” or “almost clear” (with at least a 2-point reduction from 
baseline) at Week 16. In the CIMPACT study, the primary efficacy endpoint was the proportion of 
patients achieving PASI 75 at Week 12. PASI75 and PGA at Week 16 were key secondary endpoints. 
PASI 90 at Week 16 was a key secondary endpoint in all 3 studies.  
 
CIMPASI-1 and CIMPASI-2 evaluated 234 patients and 227 patients respectively. In both studies 
patients were randomized to receive placebo or Cimzia 200 mg every 2 weeks (following a loading 
dose of Cimzia 400 mg at Weeks 0, 2 and 4) or Cimzia 400 mg every 2 weeks. At week 16, patients 
randomized to Cimzia who achieved a PASI 50 response continued to receive Cimzia up to 
Week 48 at the same randomized dose. Patients originally randomized to placebo that achieved a 
PASI 50 response but not a PASI 75 response at Week 16 received Cimzia 200 mg every 2 weeks 
(with a loading dose of Cimzia 400 mg at Weeks 16, 18, and 20). Patients with an inadequate response 
at Week 16 (PASI 50 non-responders) were eligible to receive Cimzia 400 mg every 2 weeks in an 
open-label manner for a maximum of 128 weeks.  
 
The CIMPACT study evaluated 559 patients. Patients were randomized to receive placebo, or 
Cimzia 200 mg every 2 weeks (following a loading dose of Cimzia 400 mg at Weeks 0, 2 and 4), or 
Cimzia 400 mg every 2 weeks up to Week 16, or etanercept 50 mg twice weekly, up to Week 12. 
Patients originally randomized to Cimzia who achieved a PASI75 response at Week 16 were re-
randomized based on their original dosing schedule. Patients on Cimzia 200 mg every 2 weeks were 
re-randomized to Cimzia 200 mg every 2 weeks, Cimzia 400 mg every 4 weeks or placebo. Patient on 
Cimzia 400 mg every 2 weeks were re-randomized to Cimzia 400 mg every 2 weeks, Cimzia 200 mg 
every 2 weeks, or placebo. Patients were evaluated in a double-blind placebo-controlled manner 
through Week 48. All subjects who did not achieve a PASI 75 response at Week 16 entered an escape 
arm and received Cimzia 400 mg every 2 weeks in an open-label manner for a maximum of 128 
weeks. 
 
In all three studies, the blinded 48-week maintenance period was followed by a 96-week open-label 
treatment period for the patients who were PASI 50 responders at Week 48. All these patients, 
including those receiving Cimzia 400 mg every 2 weeks, started the open-label period at Cimzia 200 
mg every 2 weeks. 
 
Patients were predominantly men (64%) and Caucasian (94%), with a mean age of 45.7 years 
(18 to 80 years); of these, 7.2% were ≥ 65 years of age. Of the 850 patients randomized to receive 
placebo or Cimzia in these placebo-controlled studies, 29% of patients were naïve to prior systemic 
therapy for the treatment of psoriasis. 47% had received prior phototherapy or chemophototherapy, 
and 30% had received prior biologic therapy for the treatment of psoriasis. Of the 850 patients, 14% 
had received at least one TNF-antagonist, 13% had received an anti-IL-17, and 5% had received an 



58 

anti-IL 12/ 23. Eighteen percent of patients reported a history of psoriatic arthritis at baseline. The 
mean PASI score at baseline was 20 and ranged from 12 to 69. The baseline PGA score ranged from 
moderate (70%) to severe (30%). Mean baseline BSA was 25% and ranged from 10% to 96%. 
 
 
Clinical response at Week 16 and 48 
The key results of CIMPASI-1 and CIMPASI-2 studies are presented in Table 12. 
 
Table 12  Clinical response in studies CIMPASI-1 and CIMPASI-2 at Week 16 and Week 48 
 Week 16 Week 48 
CIMPASI-1 
 Placebo 

 
N=51 

Cimzia 200 mg 
Q2W a) 
N=95 

Cimzia 400 mg 
Q2W 
N=88 

Cimzia 200 mg 
Q2W 
N=95 

Cimzia 400 mg 
Q2W 
N=88 

PGA clear or 
almost clearb) 

4.2% 47.0%* 57.9%* 52.7% 69.5% 

PASI 75 6.5% 66.5%* 75.8%* 67.2% 87.1% 
PASI 90 0.4% 35.8%* 43.6%* 42.8% 60.2% 
CIMPASI-2 
 Placebo 

 
N=49 

Cimzia 200 mg 
Q2W a) 
N=91 

Cimzia 400 mg 
Q2W 
N=87 

Cimzia 200 mg 
Q2W 
N= 91 

Cimzia 400 mg 
Q2W 
N= 87 

PGA clear or 
almost clearb) 

2.0% 66.8%* 71.6%* 72.6% 66.6% 

PASI 75 11.6% 81.4%* 82.6%* 78.7% 81.3% 
PASI 90 4.5% 52.6%* 55.4%* 59.6% 62.0% 
a) Cimzia 200 mg administered every 2 weeks preceded by a loading dose of 400 mg at Week 0, 2, 4. 
b) PGA 5 category scale. Treatment success of “clear” (0) or “almost clear”(1) consisted of no signs of 
psoriasis or normal to pink coloration of lesions, no thickening of the plaque, and none to minimal 
focal scaling. 
* Cimzia vs placebo: p< 0.0001.  
Response rates and p-values for PASI and PGA were estimated based on a logistic regression model 
where missing data were imputed using multiple imputation based on the MCMC method. Subject 
who escaped or withdrew (based on not achieving PASI 50 response) were treated as non-responders 
at Week 48. 
Results are from the Randomized Set. 
 
The key results of the CIMPACT trial are presented in Table13. 
 
Table13  Clinical response in CIMPACT study at Week 12 and Week 16 
 Week 12 Week 16 
 Placebo 

N=57 
Cimzia 200 
mg Q2W a) 

N=165 

Cimzia 400 
mg Q2W 
N=167 

Etanercept 5
0 mg BiW 

N=170 

Placebo 
N=57 

Cimzia 200 
mg Q2W 
N=165 

Cimzia 400 
mg 

Q2W 
N=167 

PASI 75 5% 61.3%*,§ 66.7%*,§§ 53.3% 3.8% 68.2%* 74.7%* 
PASI 90 0.2% 31.2%* 34.0%* 27.1% 0.3% 39.8%* 49.1%* 
PGA clear or 
almost clear b) 1.9% 39.8%** 50.3%* 39.2% 3.4% 48.3%* 58.4%* 
a) Cimzia 200 mg administered every 2 weeks preceded by a loading dose of 400 mg at Week 0, 2, 4. 
b) PGA 5 category scale. Treatment success of “clear” (0) or “almost clear”(1) consisted of no signs of 
psoriasis or normal to pink coloration of lesions, no thickening of the plaque, and none to minimal 
focal scaling. 
* Cimzia vs placebo: p< 0.0001.  



59 

§ Cimzia 200 mg every 2 weeks versus etanercept 50 mg twice weekly demonstrated non-inferiority 
(difference between etanercept and Cimzia 200 mg every 2 weeks was 8.0%, 95% CI -2.9, 18.9, based 
on a pre-specified non-inferiority margin of 10%). 
§§ Cimzia 400 mg every 2 weeks versus etanercept 50 mg twice weekly demonstrated superiority 
(p<0.05) 
** Cimzia vs Placebo p< 0.001. Response rates and p-values based on a logistic regression model.  
Missing data were imputed using multiple imputation based on the MCMC method. Results are from 
the Randomized Set. 
 
In all 3 studies, the PASI 75 response rate was significantly greater for Cimzia compared to placebo 
starting at Week 4. 
 
Both doses of Cimzia demonstrated efficacy compared to placebo regardless of age, gender, body 
weight, BMI, psoriasis disease duration, previous treatment with systemic therapies and previous 
treatment with biologics.  
 
Maintenance of response  
In an integrated analysis of  CIMPASI-1 and CIMPASI-2, among patients who were PASI 75 
responders at Week 16 and received Cimzia 400 mg every 2 weeks (N=134 of 175 randomised 
subjects) or Cimzia 200 mg every 2 weeks (N=132 of 186 randomised subjects), the maintenance of 
response at Week 48 was 98.0% and 87.5%, respectively. Among patients who were PGA clear or 
almost clear at Week 16 and received Cimzia 400 mg every 2 weeks (N=103 of 175) or Cimzia 200 
mg every 2 weeks (N=95 of 186), the maintenance of response at Week 48 was 85.9% and 84.3% 
respectively. 
 
After an additional 96 weeks of open-label treatment (Week 144) the maintenance of response was 
evaluated. Twenty-one percent of all randomised subjects were lost to follow-up before Week 144. 
Approximately 27% of completer study subjects who entered the open-label treatment between weeks 
48 to 144 on Cimzia 200 mg every 2 weeks had their dose increased to Cimzia 400 mg every 2 weeks 
for maintenance of response. In an analysis in which all patients with treatment failures were 
considered non-responders, the maintenance of response of the Cimzia 200 mg every 2 weeks 
treatment group for the respective endpoint, after an additional 96 weeks of open-label therapy, was 
84.5% for PASI 75 for study subjects who were responders at Week 16  and 78.4% for PGA clear or 
almost clear. The maintenance of response of the Cimzia 400 mg every 2 weeks treatment group, who 
entered the open-label period at Cimzia 200 mg every 2 weeks, was 84.7% for PASI 75 for study 
subjects who were responders at Week 16 and 73.1% for PGA clear or almost clear.  
 
These response rates were based on a logistic regression model where missing data were imputed over 
48 or 144 weeks using multiple imputation (MCMC method) combined with NRI for treatment 
failures.  
 
In the CIMPACT study, among PASI 75 responders at Week 16 who received Cimzia 400 mg every 2 
weeks and were re-randomized to either Cimzia 400 mg every 2 weeks, Cimzia 200 mg every 2 
weeks, or placebo, there was a higher percentage of PASI 75 responders at Week 48 in the Cimzia 
groups as compared to placebo (98.0%, 80.0%, and 36.0%, respectively). Among PASI75 responders 
at Week 16 who received Cimzia 200 mg every 2 weeks and were re-randomized to either Cimzia 400 
mg every 4 weeks, Cimzia 200 mg every 2 weeks, or placebo, there was also a higher percentage of 
PASI 75 responders at Week 48 in the Cimzia groups as compared to placebo (88.6%, 79.5%, and 
45.5%, respectively). Non-responder imputation was used for missing data. 
 
Quality of life / Patient reported outcomes 
 
Statistically significant improvements at Week 16 (CIMPASI-1 and CIMPASI-2) from baseline 
compared to placebo were demonstrated in the DLQI (Dermatology Life Quality Index). Mean 
decreases (improvements) in DLQI from baseline ranged from -8.9 to -11.1 with Cimzia 200 mg every 



60 

2 weeks, from -9.6 to -10.0 with Cimzia 400 mg every 2 weeks, versus -2.9 to -3.3 for placebo at 
Week 16.  
 
In addition, at Week 16, Cimzia treatment was associated with a greater proportion of patients 
achieving a DLQI score of  0 or 1 (Cimzia 400 mg every 2 weeks, 45.5% and 50.6% respectively; 
Cimzia 200 mg every 2 weeks, 47.4% and 46.2% respectively, versus placebo, 5.9% and 8.2% 
respectively).  
 
Improvements in DLQI score were sustained or slightly decreased through Week 144. 
 
Cimzia-treated patients reported greater improvements compared to placebo in the Hospital Anxiety 
and Depression Scale (HADS)-D. 
 
Immunogenicity 
 
The data below reflect the percentage of patients whose test results were considered positive for 
antibodies to certolizumab pegol in an ELISA and later in a more sensitive method, and are highly 
dependent on the sensitivity and specificity of the assay.  The observed incidence of antibody 
(including neutralizing antibody) positivity in an assay is highly dependent on several factors, 
including assay sensitivity and specificity, assay methodology, sample handling, timing of sample 
collection, concomitant medications, and underlying disease. For these reasons, comparison of the 
incidence of antibodies to certolizumab pegol in the studies described below with the incidence of 
antibodies in other studies or to other products may be misleading. 
 
Rheumatoid arthritis 
The overall percentage of patients with antibodies to Cimzia detectable on at least 1 occasion 
was 9.6% in RA placebo-controlled trials. Approximately one-third of antibody-positive patients had 
antibodies with neutralising activity in vitro. Patients treated with concomitant immunosuppressants 
(MTX) had a lower rate of antibody development than patients not taking immunosuppressants at 
baseline. Antibody formation was associated with lowered drug plasma concentration and in some 
patients, reduced efficacy. 
 
In 2 long-term (up to 5 years of exposure) open-label studies, the overall percentage of patients with 
antibodies to Cimzia detectable on at least one occasion was 13% (8.4% of the overall patients had 
transient formation of antibodies and an additional 4.7% had persistent formation of antibodies to 
Cimzia). The overall percentage of patients that were antibody positive with a persistent reduction of 
drug plasma concentration was estimated to be 9.1%. Similar to the placebo-controlled studies, 
antibody positivity was associated with reduced efficacy in some patients. 
 
A pharmacodynamic model based on the Phase III trial data predicts that around 15% of the patients 
develop antibodies in 6 months at the recommended dose regimen (200 mg every 2 weeks following a 
loading dose) without MTX co-treatment. This number decreases with increasing doses of 
concomitant MTX treatment. These data are reasonably in agreement with observed data. 
 
 
Psoriatic arthritis 
The overall percentage of patients with antibodies to Cimzia detectable on at least one occasion up to 
Week 24 was 11.7% in the Phase III placebo-controlled trial in patients with psoriatic arthritis. 
Antibody formation was associated with lowered drug plasma concentration.  
Over the course of the entire study (up to 4 years of exposure), the overall percentage of patients with 
antibodies to Cimzia detectable on at least one occasion was 17.3% (8.7% had transient formation and 
an additional 8.7% had persistent formation of antibodies to Cimzia). The overall percentage of 
patients that were antibody positive with a persistent reduction of drug plasma concentration was 
estimated to be 11.5%. 
 



61 

Plaque psoriasis 
In the Phase III placebo- and active-controlled studies, the percentages of patients who were positive 
for antibodies to Cimzia on at least one occasion during treatment up to Week 48 were 8.3 % (22/265) 
and 19.2% (54/281) for the Cimzia 400 mg every 2 weeks and Cimzia 200 mg every 2 weeks 
respectively. In CIMPASI-1 and CIMPASI-2, sixty patients were antibody positive, 27 of these 
patients were evaluable for neutralizing antibodies and tested positive. First occurrences of antibody 
positivity in the open-label treatment period were observed in 2.8% (19/668) of patients. Antibody 
positivity was associated with lowered drug plasma concentration and in some patients with reduced 
efficacy. 
 
Axial spondyloarthritis 
AS001 
The overall percentage of patients with antibodies to Cimzia detectable on at least one occasion up to 
Week 24 was 4.4% in the AS001 phase III placebo-controlled trial in patients with axial 
spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis 
subpopulations). Antibody formation was associated with lowered drug plasma concentration. 

Over the course of the entire study (up to 192 weeks), the overall percentage of patients with 
antibodies to Cimzia detectable on at least one occasion was 9.6% (4.8% had transient formation and 
an additional 4.8% had persistent formation of antibodies to Cimzia). The overall percentage of 
patients that were antibody positive with a persistent reduction of drug plasma concentration was 
estimated to be 6.8%. 
 
AS0006 and C-OPTIMISE  
A more sensitive and drug tolerant assay was used for the first time in the AS0006 study (and later 
also in the C-OPTIMISE study), resulting in a greater proportion of samples having measurable 
antibodies to Cimzia and thus a greater incidence of patients being classed as antibody positive. In 
AS0006,  the overall incidence of patients who were antibody positive to Cimzia was 97% 
(248/255 patients) after up to 52 weeks of treatment. Only the highest titers were associated with 
reduced Cimzia plasma levels, however, no impact on efficacy was observed. Similar results in 
relation to antibodies to Cimzia were seen in C-OPTIMISE. Results from C-OPTIMISE also indicated 
that a reduction of the dose to Cimzia 200 mg every 4 weeks did not change immunogenicity 
outcomes. 
 
About 22% (54/248) of the patients in AS0006 who were anti-Cimzia antibody positive at any time, 
had antibodies that were classified as neutralizing. The neutralizing status of antibodies in C-
OPTIMISE was not assessed. 
 
5.2 Pharmacokinetic properties 
 
Certolizumab pegol plasma concentrations were broadly dose-proportional. Pharmacokinetics 
observed in patients with rheumatoid arthritis and psoriasis were consistent with those seen in healthy 
subjects. 
 
Absorption 
Following subcutaneous administration, peak plasma concentrations of certolizumab pegol were 
attained between 54 and 171 hours post-injection. Certolizumab pegol has a bioavailability (F) of 
approximately 80% (range 76% to 88%) following subcutaneous administration compared to 
intravenous administration. 
 
Distribution 
The apparent volume of distribution (V/F) was estimated at 8.01 l in a population pharmacokinetic 
analysis of patients with rheumatoid arthritis and at 4.71 l in a population pharmacokinetic analysis of 
patients with plaque psoriasis. 
 



62 

Biotransformation and elimination 
PEGylation, the covalent attachment of PEG polymers to peptides, delays the elimination of these 
entities from the circulation by a variety of mechanisms, including decreased renal clearance, 
decreased proteolysis, and decreased immunogenicity. Accordingly, certolizumab pegol is an antibody 
Fab' fragment conjugated with PEG in order to extend the terminal plasma elimination half-life of the 
Fab' to a value comparable with a whole antibody product. The terminal elimination phase half-life 
(t1/2) was approximately 14 days for all doses tested.  
 
Clearance following subcutaneous dosing was estimated to be 21.0 ml/h in a rheumatoid arthritis 
population pharmacokinetic analysis, with an inter-subject variability of 30.8% (CV) and an inter-
occasion variability of 22.0%. When assessed using the previous ELISA method, the presence of 
antibodies to certolizumab pegol resulted in an approximately three-fold increase in clearance. 
Compared with a 70 kg person, clearance is 29% lower and 38% higher, respectively, in individual RA 
patients weighing 40 kg and 120 kg. The clearance following subcutaneous dosing in patients with 
psoriasis was 14 ml/h with an inter-subject variability of 22.2% (CV). 
 
The Fab' fragment comprises protein compounds and is expected to be degraded to peptides and amino 
acids by proteolysis. The de-conjugated PEG component is rapidly eliminated from plasma and is to 
an unknown extent excreted renally. 
 
Special populations 
Renal impairment 
Specific clinical trials have not been performed to assess the effect of renal impairment on the 
pharmacokinetics of certolizumab pegol or its PEG fraction. However, population pharmacokinetic 
analysis based on subjects with mild renal impairment showed no effect of creatinine clearance. There 
are insufficient data to provide a dosing recommendation in moderate and severe renal impairment. 
The pharmacokinetics of the PEG fraction of certolizumab pegol are expected to be dependent on 
renal function but have not been assessed in patients with renal impairment. 
 
Hepatic impairment 
Specific clinical trials have not been performed to assess the effect of hepatic impairment on the 
pharmacokinetics of certolizumab pegol. 
 
Elderly patients (≥ 65 years old) 
Specific clinical trials have not been performed in elderly patients subjects. However, no effect of age 
was observed in a population pharmacokinetic analysis in patients with rheumatoid arthritis in 
which 78 subjects (13.2% of the population) were aged 65 or greater and the oldest subject was 
aged 83 years. No effect of age was observed in a population pharmacokinetic analysis in adult 
patients with plaque psoriasis. 
 
Gender 
There was no effect of gender on the pharmacokinetics of certolizumab pegol. As clearance decreases 
with decreasing body weight, females may generally obtain somewhat higher systemic exposure of 
certolizumab pegol. 
 
Pharmacokinetic/pharmacodynamic relationship 
On the basis of Phase II and Phase III clinical trial data in patients with rheumatoid arthritis, a 
population exposure-response relationship was established between average plasma concentration of 
certolizumab pegol during a dosing interval (Cavg) and efficacy (ACR 20 responder definition). The 
typical Cavg that produces half the maximum probability of ACR 20 response (EC50) was 17 µg/ml 
(95% CI: 10-23 µg/ml). Similarly, on the basis of Phase III clinical trial data in patients with psoriasis, 
a population exposure-response relationship was established between plasma concentration of 
certolizumab pegol and PASI with an EC90 of 11.1 µg/ml. 
 



63 

5.3 Preclinical safety data 
 
The pivotal non-clinical safety studies were conducted in the cynomolgus monkey. In rats and 
monkeys, at doses higher than those given to humans, histopathology revealed cellular vacuolation, 
present mainly in macrophages, in a number of organs (lymph nodes, injection sites, spleen, adrenal, 
uterine, cervix, choroid plexus of the brain, and in the epithelial cells of the choroid plexus). It is likely 
that this finding was caused by cellular uptake of the PEG moiety. In vitro functional studies of human 
vacuolated macrophages indicated all functions tested were retained. Studies in rats indicated that 
> 90% of the administered PEG was eliminated in 3 months following a single dose, with the urine 
being the main route of excretion. 
 
Certolizumab pegol does not cross-react with rodent TNF. Therefore, reproductive toxicology studies 
have been performed with a homologous reagent recognising rat TNF. The value of these data to the 
evaluation of human risk may be limited. No adverse effects were seen on maternal well-being or 
female fertility, embryo-foetal and peri- and post-natal reproductive indices in rats using a rodent anti-
rat TNFα PEGylated Fab' (cTN3 PF) following sustained TNFα suppression. In male rats, reduced 
sperm motility and a trend of reduced sperm count were observed. 
 
Distribution studies have demonstrated that placental and milk transfer of cTN3 PF to the foetal and 
neonatal circulation is negligible. Certolizumab pegol does not bind to the human neonatal Fc receptor 
(FcRn). Data from a human closed-circuit placental transfer model ex vivo suggest low or negligible 
transfer to the foetal compartment. In addition, experiments of FcRn-mediated transcytosis in cells 
transfected with human FcRn showed negligible transfer (see section 4.6).  
 
No mutagenic or clastogenic effects were demonstrated in preclinical studies. Carcinogenicity studies 
have not been performed with certolizumab pegol. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium acetate 
Sodium chloride 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
2 years. 
See also section 6.4 for shelf-life related to storage at room temperature up to a maximum of 25°C. 
 
6.4 Special precautions for storage 
 
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. 
The pre-filled pens may be stored at room temperature (up to 25°C) for a single period of 
maximum 10 days with protection from light. At the end of this period the pre-filled pens must be 
used or discarded. 
 



64 

6.5 Nature and contents of container 
 
One ml pre-filled pen (AutoClicks) containing a pre-filled syringe (type I glass) with a plunger stopper 
(bromobutyl rubber), containing 200 mg of certolizumab pegol. The needle shield is styrene butadiene 
rubber which contains a derivative of natural rubber latex (see section 4.4). 
  
Pack size of 2 pre-filled pens and 2 alcohol wipes, a multipack containing 6 (3 packs of 2) pre-filled 
pens and 6 (3 packs of 2) alcohol wipes, a multipack of 10 (5 packs of 2) pre-filled pens 
and 10 (5 packs of 2) alcohol wipes 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Comprehensive instructions for the preparation and administration of Cimzia in a pre-filled pen are 
given in the package leaflet. 
This medicinal product is for single use only. Any unused product or waste material should be 
disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
B-1070 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/005  
EU/1/09/544/006 
EU/1/09/544/007  
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 01 October 2009 
Date of latest renewal: 16 May 2014 
 
 
10. DATE OF REVISION OF THE TEXT 
 
{MM/YYYY} 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 
 



65 

1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in dose-dispenser cartridge 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each dose-dispenser cartridge contains 200 mg certolizumab pegol in one ml. 
 
Certolizumab pegol is a recombinant, humanised antibody Fab' fragment against tumour necrosis 
factor alpha (TNFα) expressed in Escherichia coli and conjugated to polyethylene glycol (PEG). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection (injection). 
 
Clear to opalescent, colourless to yellow solution. The pH of the solution is approximately 4.7. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Rheumatoid arthritis 
Cimzia, in combination with methotrexate (MTX), is indicated for: 
 the treatment of moderate to severe, active rheumatoid arthritis (RA) in adult patients when the 

response to disease-modifying antirheumatic drugs (DMARDs) including MTX, has been 
inadequate. Cimzia can be given as monotherapy in case of intolerance to MTX or when 
continued treatment with MTX is inappropriate 

 
 the treatment of severe, active and progressive RA in adults not previously treated with MTX or 

other DMARDs. 
 
Cimzia 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 MTX. 
 
Axial spondyloarthritis 
Cimzia is indicated for the treatment of adult patients with severe active axial spondyloarthritis, 
comprising:  
 
Ankylosing spondylitis (AS) (also known as radiographic axial spondyloarthritis) 
Adults with severe active ankylosing spondylitis who have had an inadequate response to, or are 
intolerant to nonsteroidal anti-inflammatory drugs (NSAIDs).  

 
Axial spondyloarthritis without radiographic evidence of AS (also known as non-radiographic axial 
spondyloarthritis) 
Adults with severe active axial spondyloarthritis without radiographic evidence of AS but with 
objective signs of inflammation by elevated C-reactive protein (CRP) and /or magnetic resonance 
imaging (MRI), who have had an inadequate response to, or are intolerant to NSAIDs. 
 
Psoriatic arthritis  
Cimzia, in combination with MTX, is indicated for the treatment of active psoriatic arthritis in adults 
when the response to previous DMARD therapy has been inadequate. 
 



66 

Cimzia can be given as monotherapy in case of intolerance to methotrexate or when continued 
treatment with methotrexate is inappropriate. 
 
Plaque psoriasis 
Cimzia is indicated for the treatment of moderate to severe plaque psoriasis in adults who are 
candidates for systemic therapy. 
 
For details on therapeutic effects, see section 5.1. 
 
4.2 Posology and method of administration 
 
Treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and 
treatment of conditions for which Cimzia is indicated. Patients should be given the special reminder 
card. 
 
Posology 
 
Rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, plaque psoriasis 
 
Loading dose 
The recommended starting dose of Cimzia for adult patients is 400 mg (given 
as 2 subcutaneous injections of 200 mg each) at weeks 0, 2 and 4. For rheumatoid arthritis and 
psoriatic arthritis, MTX should be continued during treatment with Cimzia where appropriate. 
 
Maintenance dose 
Rheumatoid arthritis 
After the starting dose, the recommended maintenance dose of Cimzia for adult patients with 
rheumatoid arthritis is 200 mg every 2 weeks. Once clinical response is confirmed, an alternative 
maintenance dosing of 400 mg every 4 weeks can be considered. MTX should be continued during 
treatment with Cimzia where appropriate. 
 
Axial spondyloarthritis 
After the starting dose, the recommended maintenance dose of Cimzia for adult patients with axial 
spondyloarthritis is 200 mg every 2 weeks or 400 mg every 4 weeks. After at least 1 year of treatment 
with Cimzia, in patients with sustained remission, a reduced maintenance dose of 200 mg every 4 
weeks may be considered (see section 5.1). 
 
Psoriatic arthritis 
After the starting dose, the recommended maintenance dose of Cimzia for adult patients with psoriatic 
arthritis is 200 mg every 2 weeks. Once clinical response is confirmed, an alternative maintenance 
dosing of 400 mg every 4 weeks can be considered. MTX should be continued during treatment with 
Cimzia where appropriate. 
 
For the above indications, available data suggest that clinical response is usually achieved 
within 12 weeks of treatment. Continued therapy should be carefully reconsidered in patients who 
show no evidence of therapeutic benefit within the first 12 weeks of treatment. 
 
Plaque psoriasis 
After the starting dose, the maintenance dose of Cimzia for adult patients with plaque psoriasis 
is 200 mg every 2 weeks. A dose of 400 mg every 2 weeks can be considered in patients with 
insufficient response (see section 5.1). 
  
Available data in adults with plaque psoriasis suggest that a clinical response is usually achieved 
within 16 weeks of treatment. Continued therapy should be carefully reconsidered in patients who 
show no evidence of therapeutic benefit within the first 16 weeks of treatment. Some patients with an 
initial partial response may subsequently improve with continued treatment beyond 16 weeks. 
 



67 

Missed dose 
Patients who miss a dose should be advised to inject the next dose of Cimzia as soon as they 
remember and then continue injecting subsequent doses as instructed. 
 
Special populations 
Paediatric population (< 18 years old) 
The safety and efficacy of Cimzia in children and adolescents below age 18 years have not yet been 
established. No data are available. 
 
Elderly patients (≥ 65 years old) 
No dose adjustment is required. Population pharmacokinetic analyses showed no effect of age (see 
section 5.2). 
 
Renal and hepatic impairment 
Cimzia has not been studied in these patient populations. No dose recommendations can be made (see 
section 5.2). 
 
Method of administration 
The total content (1 ml) of the dose-dispenser cartridge should be administered using the 
electromechanical injection device ava for a subcutaneous injection only. Suitable sites for injection 
would include the thigh or abdomen. 
 
Cimzia solution for injection in a dose-dispenser cartridge is intended for single-use in conjunction 
with the electromechanical injection device named ava. After proper training in the injection 
technique, patients may self-inject using the electromechanical injection device ava with the single-use 
dose-dispenser cartridge if their physician determines that it is appropriate and with medical follow-up 
as necessary. The physician should discuss with the patient which injection presentation option is the 
most appropriate.  
 
The ava injection device currently does not support administration of a maintenance dose of 400 mg 
every 2 weeks (plaque psoriasis) or a reduced maintenance dose of 200 mg every 4 weeks (axial 
spondyloarthritis); for patients receiving these maintenance doses, the physician is advised to use other 
presentations. 
 
For administration, the instructions for use at the end of the package leaflet and in the user manual 
provided with the electromechanical injection device ava should be followed. 
 
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 or opportunistic infections (see 
section 4.4). 
 
Moderate to severe heart failure (NYHA classes 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 must be monitored closely for signs and symptoms of infections including tuberculosis before, 
during and after treatment with Cimzia. Because the elimination of certolizumab pegol may take up 
to 5 months, monitoring should be continued throughout this period (see section 4.3). 
 



68 

Treatment with Cimzia must not be initiated in patients with a clinically important active infection, 
including chronic or localised infections, until the infection is controlled (see section 4.3).  
 
Patients who develop a new infection while undergoing treatment with Cimzia should be monitored 
closely. Administration of Cimzia should be discontinued if a patient develops a new serious infection 
until the infection is controlled. Physicians should exercise caution when considering the use of 
Cimzia in patients with a history of recurring or opportunistic infection or with underlying conditions 
which may predispose patients to infections, including the use of concomitant immunosuppressive 
medications. 
 
Patients with rheumatoid arthritis may not manifest typical symptoms of infection, including fever, 
due to their disease and concomitant medicinal products. Therefore, early detection of any infection, 
particularly atypical clinical presentations of a serious infection, is critical to minimise delays in 
diagnosis and initiation of treatment. 
 
Serious infections, including sepsis and tuberculosis (including miliary, disseminated and 
extrapulmonary disease), and opportunistic infections (e.g. histoplasmosis, nocardia, candidiasis) have 
been reported in patients receiving Cimzia. Some of these events have been fatal. 
 
Tuberculosis 
Before initiation of therapy with Cimzia, all patients must be evaluated for both active or inactive 
(latent) tuberculosis infection. This evaluation should include a detailed medical history for patients 
with a personal history of tuberculosis, with possible previous exposure to others with active 
tuberculosis, and with previous and/or current use of immunosuppressive therapy. Appropriate 
screening tests, e.g. tuberculin skin test and chest X-ray, should be performed in all patients (local 
recommendations may apply). It is recommended that the conduct of these tests should be recorded in 
the patient's 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 prior to or during treatment, Cimzia therapy must not be initiated 
and must be discontinued (see section 4.3). 
 
If inactive (‘latent’) tuberculosis is suspected, a physician with expertise in the treatment of 
tuberculosis should be consulted. In all situations described below, the benefit/risk balance of Cimzia 
therapy should be very carefully considered. 
 
If latent tuberculosis is diagnosed, appropriate anti-tuberculosis therapy must be started before 
initiating treatment with Cimzia and in accordance with local recommendations.  
Use of anti-tuberculosis therapy should also be considered before the initiation of Cimzia in patients 
with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be 
confirmed, and in patients who have significant risk factors for tuberculosis despite a negative test for 
latent tuberculosis. Biological tests for tuberculosis screening should be considered before starting 
Cimzia treatment if there is any potential latent tuberculosis infection, regardless of BCG vaccination. 
 
Despite previous or concomitant prophylactic treatment for tuberculosis, cases of active tuberculosis 
have occurred in patients treated with TNF-antagonists including Cimzia. Some patients who have 
been successfully treated for active tuberculosis have redeveloped tuberculosis while being treated 
with Cimzia. 
 
Patients should be instructed to seek medical advice if signs/symptoms (e.g. persistent cough, 
wasting/weight loss, low grade fever, listlessness) suggestive of a tuberculosis infection occur during 
or after therapy with Cimzia. 
 
Hepatitis B virus (HBV) reactivation 
Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including certolizumab 
pegol, who are chronic carriers of this virus (i.e., surface antigen positive). Some cases have had a 
fatal outcome.  



69 

 
Patients should be tested for HBV infection before initiating treatment with Cimzia. For patients who 
test positive for HBV infection, consultation with a physician with expertise in the treatment of 
hepatitis B is recommended.  
 
Carriers of HBV who require treatment with Cimzia should be closely monitored for signs and 
symptoms of active HBV infection throughout therapy and for several months following termination 
of therapy. Adequate data of 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, Cimzia should be stopped and effective anti-viral therapy with 
appropriate supportive treatment should be initiated. 
 
Malignancies and lymphoproliferative disorders 
The potential role of TNF-antagonist therapy in the development of malignancies is not known. 
Caution should be exercised when considering TNF-antagonist therapy for patients with a history of 
malignancy or when considering continuing treatment in patients who develop malignancy.  
 
With the current knowledge, a possible risk for the development of lymphomas, leukaemia or other 
malignancies in patients treated with a TNF-antagonist cannot be excluded. 
 
In clinical trials with Cimzia and other TNF-antagonists, more cases of lymphoma and other 
malignancies have been reported among patients receiving TNF-antagonists than in control patients 
receiving placebo (see section 4.8). 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. 
 
No trials have been conducted that include patients with a history of malignancy, or that continue 
treatment in patients who develop malignancy, while receiving Cimzia.  
 
Skin cancers 
Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-antagonists 
including certolizumab pegol (see section 4.8). Periodic skin examination is recommended, 
particularly for patients with risk factors for skin cancer. 
 
Paediatric malignancy 
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) 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. 
 
Post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL), have been reported in patients 
treated with TNF-antagonists. This rare type of T-cell lymphoma has a very aggressive disease course 
and is usually fatal. The majority of reported TNF-antagonist cases occurred in adolescent and young 
adult males with Crohn’s disease or ulcerative colitis. Almost all of these patients had received 
treatment with the immunosuppressants azathioprine and/or 6-mercaptopurine concomitantly with a 
TNF-antagonist at or prior to diagnosis. A risk for development of hepatosplenic T-cell lymphoma in 
patients treated with Cimzia cannot be excluded. 
 
Chronic obstructive pulmonary disease (COPD) 
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 



70 

TNF-antagonist in COPD patients, as well as in patients with increased risk for malignancy due to 
heavy smoking. 
 
Congestive heart failure 
Cimzia is contraindicated in moderate or severe heart failure (see section 4.3). 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 congestive heart failure have also been reported in 
rheumatoid arthritis patients receiving Cimzia. Cimzia should be used with caution in patients with 
mild heart failure (NYHA class I/II). Treatment with Cimzia must be discontinued in patients who 
develop new or worsening symptoms of congestive heart failure. 
 
Haematological reactions 
Reports of pancytopaenia, including aplastic anaemia, have been rare with TNF-antagonists. Adverse 
reactions of the haematologic system, including medically significant cytopaenia (e.g. leukopaenia, 
pancytopaenia, thrombocytopaenia) have been reported with Cimzia (see section 4.8). All patients 
should be advised to seek immediate medical attention if they develop signs and symptoms suggestive 
of blood dyscrasias or infection (e.g., persistent fever, bruising, bleeding, pallor) while on Cimzia. 
Discontinuation of Cimzia therapy should be considered in patients with confirmed significant 
haematological abnormalities. 
 
Neurological events 
Use of TNF-antagonists has been associated with rare cases of new onset or exacerbation of clinical 
symptoms and/or radiographic evidence of demyelinating disease, including multiple sclerosis. In 
patients with pre-existing or recent onset of demyelinating disorders, the benefits and risks of 
TNF-antagonist treatment should be carefully considered before initiation of Cimzia therapy. Rare 
cases of neurological disorders, including seizure disorder, neuritis and peripheral neuropathy, have 
been reported in patients treated with Cimzia. 
 
Hypersensitivity 
Severe hypersensitivity reactions have been reported rarely following Cimzia administration. Some of 
these reactions occurred after the first administration of Cimzia. If severe reactions occur, 
administration of Cimzia should be discontinued immediately and appropriate therapy instituted.  
 
There are limited data on the use of Cimzia in patients who have experienced a severe hypersensitivity 
reaction towards another TNF-antagonist; in these patients caution is needed. 
 
Latex-sensitivity  
The needle shield inside the removable cap of the CIMZIA dose-dispenser cartridge contains a 
derivative of natural rubber latex (see section 6.5). Contact with natural rubber latex may cause severe 
allergic reactions in individuals sensitive to latex. No antigenic latex protein has to date been detected 
in the removable needle cap of the Cimzia dose-dispenser cartridge. Nevertheless, a potential risk of 
hypersensitivity reactions cannot be completely excluded in latex-sensitive individuals. 
 
Immunosuppression 
Since tumour necrosis factor (TNF) mediates inflammation and modulates cellular immune responses, 
the possibility exists for TNF-antagonists, including Cimzia, to cause immunosupression, affecting 
host defences against infections and malignancies. 
 
Autoimmunity 
Treatment with Cimzia may result in the formation of antinuclear antibodies (ANA) and, 
uncommonly, in the development of a lupus-like syndrome (see section 4.8). The impact of long-term 
treatment with Cimzia on the development of autoimmune diseases is unknown. If a patient develops 
symptoms suggestive of a lupus-like syndrome following treatment with Cimzia, treatment must be 
discontinued. Cimzia has not been studied specifically in a lupus population (see section 4.8). 
 



71 

Vaccinations 
Patients treated with Cimzia may receive vaccinations, except for live vaccines. No data are available 
on the response to live vaccinations or the secondary transmission of infection by live vaccines in 
patients receiving Cimzia. Live vaccines should not be administered concurrently with Cimzia. 
 
In a placebo-controlled clinical trial in patients with rheumatoid arthritis, similar antibody response 
between Cimzia and placebo treatment were observed when the pneumococcal polysaccharide vaccine 
and influenza vaccine were administered concurrently with Cimzia. Patients receiving Cimzia and 
concomitant methotrexate had a lower humoral response compared with patients receiving Cimzia 
alone. The clinical significance of this is unknown.  
 
Concomitant use with other biologics 
Severe infections and neutropaenia were reported in clinical trials with concurrent use of anakinra (an 
interleukin-1 antagonist) or abatacept (a CD28 modulator) and another TNF-antagonist, etanercept, 
with no added benefit compared to TNF-antagonist therapy alone. Because of the nature of the adverse 
events seen with the combination of another TNF-antagonist with either abatacept or anakinra therapy, 
similar toxicities may also result from the combination of anakinra or abatacept and other 
TNF-antagonists. Therefore the use of certolizumab pegol in combination with anakinra or abatacept 
is not recommended (see section 4.5). 
 
Surgery 
There is limited safety experience with surgical procedures in patients treated with Cimzia. The 14-day 
half-life of certolizumab pegol should be taken into consideration if a surgical procedure is planned. 
A patient who requires surgery while on Cimzia should be closely monitored for infections, and 
appropriate actions should be taken. 
 
Activated partial thromboplastin time (aPTT) assay 
Interference with certain coagulation assays has been detected in patients treated with Cimzia. Cimzia 
may cause erroneously elevated aPTT assay results in patients without coagulation abnormalities. This 
effect has been observed with the PTT-Lupus Anticoagulant (LA) test and Standard Target Activated 
Partial Thromboplastin time (STA-PTT) Automate tests from Diagnostica Stago, and the HemosIL 
APTT-SP liquid and HemosIL lyophilised silica tests from Instrumentation Laboratories. Other aPTT 
assays may be affected as well. There is no evidence that Cimzia therapy has an effect on coagulation 
in vivo. After patients receive Cimzia, careful attention should be given to interpretation of abnormal 
coagulation results. Interference with thrombin time (TT) and prothrombin time (PT) assays have not 
been observed. 
 
Elderly patients 
In the clinical trials, there was an apparently higher incidence of infections among subjects ≥ 65 years 
of age, compared to younger subjects, although experience is limited. Caution should be exercised 
when treating the elderly patients, and particular attention paid with respect to occurrence of 
infections. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Concomitant treatment with methotrexate, corticosteroids, nonsteroidal anti-inflammatory drugs 
(NSAIDs) and analgesics showed no effect on the pharmacokinetics of certolizumab pegol based on a 
population pharmacokinetics analysis. 
 
The combination of certolizumab pegol and anakinra or abatacept is not recommended (see 
section 4.4). 
 
Co-administration of Cimzia with methotrexate had no significant effect on the pharmacokinetics of 
methotrexate. In study-to-study comparison, the pharmacokinetics of certolizumab pegol appeared 
similar to those observed previously in healthy subjects. 
 



72 

4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential  
The use of adequate contraception should be considered for women of childbearing potential. For 
women planning pregnancy, continued contraception may be considered for 5 months after the last 
Cimzia dose due to its elimination rate (see section 5.2), but the need for treatment of the woman 
should also be taken into account (see below). 
 
Pregnancy 
Data from more than 500 prospectively collected pregnancies exposed to Cimzia with known 
pregnancy outcomes, including more than 400 pregnancies exposed during the first trimester, does not 
indicate a malformative effect of Cimzia. However, the available clinical experience is too limited to, 
with a reasonable certainty, conclude that there is no increased risk associated with Cimzia 
administration during pregnancy. 
 
Animal studies using a rodent anti-rat TNFα did not reveal evidence of impaired fertility or harm to 
the foetus. However, the value of these data may be limited these are insufficient with respect to 
human reproductive toxicity (see section 5.3). Due to its inhibition of TNFα, Cimzia administered 
during pregnancy could affect normal immune response in the newborn.  
 
Cimzia should only be used during pregnancy if clinically needed. 
 
Non-clinical studies suggest low or negligible level of placental transfer of a homologue Fab-fragment 
of certolizumab pegol (no Fc region) (see section 5.3). 
 
In a clinical study 16 women were treated with certolizumab pegol (200 mg every 2 weeks or 400 mg 
every 4 weeks) during pregnancy. Certolizumab pegol plasma concentrations measured in 14 infants at 
birth were Below the Limit of Quantification (BLQ) in 13 samples; one was 0.042 µg/ml with an 
infant/mother plasma ratio at birth of 0.09%. At Week 4 and Week 8, all infant concentrations were 
BLQ. The clinical significance of low levels certolizumab pegol for infants is unknown. It is 
recommended to wait a minimum of 5 months following the mother’s last Cimzia administration 
during pregnancy before administration of live or live-attenuated vaccines (e.g. BCG vaccine), unless 
the benefit of the vaccination clearly outweighs the theoretical risk of administration of live or live-
attenuated vaccines to the infants. 
 
Breastfeeding 
In a clinical study in 17 lactating women treated with Cimzia, minimal transfer of certolizumab pegol 
from the plasma to breast milk was observed. The percentage of the maternal certolizumab pegol dose 
reaching an infant during a 24 hour period was estimated to 0.04% to 0.30 %. In addition, since 
certolizumab pegol is a protein that is degraded in the gastrointestinal tract after oral administration, 
the absolute bioavailability is expected to be very low in a breastfed infant. 
 
Consequently, Cimzia can be used during breastfeeding. 
 
Fertility 
Effects on sperm motility measures and a trend of reduced sperm count in male rodents have been 
observed with no apparent effect on fertility (see section 5.3).  
 
In a clinical trial to assess the effect of certolizumab pegol on semen quality parameters, 20 healthy 
male subjects were randomized to receive a single subcutaneous dose of 400 mg of certolizumab pegol 
or placebo. During the 14-week follow-up, no treatment effects of certolizumab pegol were seen on 
semen quality parameters compared to placebo. 
 
4.7 Effects on ability to drive and use machines 
 
Cimzia may have a minor influence on the ability to drive and use machines. Dizziness (including 
vertigo, vision disorder and fatigue) may occur following administration of Cimzia (see section 4.8). 



73 

 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Rheumatoid arthritis 
Cimzia was studied in 4,049 patients with rheumatoid arthritis in controlled and open label trials for 
up to 92 months.  
 
In the placebo-controlled studies, patients receiving Cimzia had an approximately 4 times greater 
duration of exposure compared with the placebo group. This difference in exposure is primarily due to 
patients on placebo being more likely to withdraw early. In addition, Studies RA-I and RA-II had a 
mandatory withdrawal for non-responders at Week 16, the majority of whom were on placebo. 
 
The proportion of patients who discontinued treatment due to adverse events during the controlled 
trials was 4.4% for patients treated with Cimzia and 2.7% for patients treated with placebo. 
 
The most common adverse reactions belonged to the system organ classes Infections and infestations, 
reported in 14.4% of patients on Cimzia and 8.0% of patients on placebo, General disorders and 
administration site conditions, reported in 8.8% of patients on Cimzia and 7.4% of patients on placebo, 
and Skin and subcutaneous tissue disorders, reported in 7.0% of patients on Cimzia and 2.4% of 
patients on placebo. 
 
Axial spondyloarthritis 
Cimzia was initially studied in 325 patients with active axial spondyloarthritis (including ankylosing 
spondylitis and non-radiopraphic axial spondyloarthritis) in the AS001 clinical study for up to 4 years, 
which includes a 24-week placebo-controlled phase followed by a 24-week dose-blind period and 
a 156-week open-label treatment period. Cimzia was subsequently studied in 317 patients with non-
radiographic axial spondyloarthritis in a placebo-controlled study for 52 weeks (AS0006). Cimzia was 
also studied in patients with axial spondyloarthritis (including ankylosing spondylitis and non-
radiographic axial spondyloarthritis) in a clinical study for up to 96 weeks, which included a 48-week 
open-label run-in phase (N=736) followed by a 48-week placebo-controlled phase (N=313) for 
patients in sustained remission (C-OPTIMISE). In all 3 studies, the safety profile for these patients 
was consistent with the safety profile in rheumatoid arthritis and previous experience with Cimzia. 
 
Psoriatic arthritis  
Cimzia was studied in 409 patients with psoriatic arthritis in the PsA001 clinical study for up 
to 4 years which includes a 24-week placebo-controlled phase followed by a 24-week dose-blind 
period and a 168-week open-label treatment period. The safety profile for psoriatic arthritis patients 
treated with Cimzia was consistent with the safety profile in rheumatoid arthritis and previous 
experience with Cimzia. 
 
Plaque psoriasis 
Cimzia was studied in 1112 patients with psoriasis in controlled and open-label studies for up to 3 
years. In the Phase III program, the initial and maintenance periods were followed by a 96-week open-
label treatment period (see section 5.1). The long-term safety profile of Cimzia 400 mg every 2 weeks 
and Cimzia 200 mg every 2 weeks was generally similar and consistent with previous experience with 
Cimzia. 
 
During controlled clinical trials through Week 16, the proportion of patients with serious adverse 
events was 3.5% for Cimzia and 3.7% for placebo.  
The proportion of patients who discontinued treatment due to adverse events in the controlled clinical 
studies was 1.5% for patients treated with Cimzia and 1.4% for patients treated with placebo.  
 
The most common adverse reactions reported through Week 16 belonged to the system organ classes 
Infections and infestations, reported in 6.1% of patients on Cimzia and 7% of patients on placebo, 
General disorders and administration site conditions, reported in 4.1% of patients on Cimzia and 2.3% 



74 

of patients on placebo, and Skin and subcutaneous tissue disorders, reported in 3.5% of patients on 
Cimzia and 2.8% of patients on placebo. 
 
Tabulated list of adverse reactions 
Adverse reactions based primarily on experience from the placebo-controlled clinical trials and 
postmarketing cases at least possibly related to Cimzia are listed in Table 1 below, according to 
frequency and system organ class. Frequency categories are defined as follows: Very common 
(≥ 1/10); Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1000 to < 1/100); Rare (≥ 1/10,000 to 
< 1/1000); Very rare (< 1/10,000), not known (cannot be estimated from the available data). Within 
each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 
Table 1 Adverse reactions in clinical trials and postmarketing 

System Organ Class  Frequency Adverse reactions  
Infections and 
infestations 

Common bacterial infections (including abscess), viral infections 
(including herpes zoster, papillomavirus, influenza) 

Uncommon sepsis (including multi-organ failure, septic shock), 
tuberculosis (including miliary, disseminated and 
extrapulmonary disease), fungal infections (includes 
opportunistic)  

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

Uncommon blood and lymphatic system malignancies (including 
lymphoma and leukaemia), solid organ tumours, non-
melanoma skin cancers, pre-cancerous lesions (including 
oral leukoplakia, melanocytic nevus), benign tumours 
and cysts (including skin papilloma) 

Rare gastrointestinal tumours, melanoma  
Not known Merkel cell carcinoma*, Kaposi’s sarcoma 

Blood and the lymphatic 
system disorders 

Common eosinophilic disorders, leukopaenia (including 
neutropaenia, lymphopaenia) 

Uncommon anaemia, lymphadenopathy, thrombocytopaenia, 
thrombocytosis 

Rare pancytopaenia, splenomegaly, erythrocytosis, white 
blood cell morphology abnormal 

Immune system disorders Uncommon vasculitides, lupus erythematosus, drug hypersensitivity 
(including anaphylactic shock), allergic disorders, 
auto-antibody positive 

Rare angioneurotic oedema, sarcoidosis, serum sickness, 
panniculitis (including erythema nodosum), worsening of 
symptoms of dermatomyositis** 

Endocrine disorders Rare thyroid disorders 
Metabolism and nutrition 
disorders 

Uncommon electrolyte imbalance, dyslipidaemia, appetite disorders, 
weight change 

Rare haemosiderosis 
Psychiatric disorders Uncommon anxiety and mood disorders (including associated 

symptoms) 
Rare suicide attempt, delirium, mental impairment 

Nervous system disorders Common headaches (including migraine), sensory abnormalities 
Uncommon peripheral neuropathies, dizziness, tremor 
Rare seizure, cranial nerve inflammation, impaired 

coordination or balance 
Not known multiple sclerosis*, Guillain-Barré syndrome* 

Eye disorders Uncommon visual disorder (including decreased vision), eye and 
eyelid inflammation, lacrimation disorder 

Ear and labyrinth 
disorders 

Uncommon tinnitus, vertigo 



75 

System Organ Class  Frequency Adverse reactions  
Cardiac disorders Uncommon cardiomyopathies (including heart failure), ischaemic 

coronary artery disorders, arrhythmias (including atrial 
fibrillation), palpitations 

Rare pericarditis, atrioventricular block 
Vascular disorders Common hypertension 

Uncommon haemorrhage or bleeding (any site), hypercoagulation 
(including thrombophlebitis, pulmonary embolism), 
syncope, oedema (including peripheral, facial), 
ecchymoses (including haematoma, petechiae) 

Rare cerebrovascular accident, arteriosclerosis, Raynaud’s 
phenomenon, livedo reticularis, telangiectasia 

Respiratory, thoracic and 
mediastinal disorders 

Uncommon asthma and related symptoms, pleural effusion and 
symptoms, respiratory tract congestion and 
inflammation, cough 

Rare interstitial lung disease, pneumonitis 
Gastrointestinal disorders Common nausea 

Uncommon ascites, gastrointestinal ulceration and perforation, 
gastrointestinal tract inflammation (any site), stomatitis, 
dyspepsia, abdominal distension, oropharyngeal dryness 

Rare odynophagia, hypermotility 
Hepatobiliary disorders Common hepatitis (including hepatic enzyme increased) 

Uncommon hepatopathy (including cirrhosis), cholestasis, blood 
bilirubin increased 

Rare cholelithiasis 
Skin and subcutaneous 
tissue disorders 

Common rash 
Uncommon alopecia, new onset or worsening of psoriasis (including 

palmoplantar pustular psoriasis) and related conditions, 
dermatitis and eczema, sweat gland disorder, skin ulcer, 
photosensitivity, acne, skin discolouration, dry skin, nail 
and nail bed disorders 

Rare skin exfoliation and desquamation, bullous conditions, 
hair texture disorder, Stevens-Johnson syndrome**, 
erythema multiforme**, lichenoid reactions 

Musculoskeletal, 
connective tissue and 
bone disorders 

Uncommon muscle disorders, blood creatine phosphokinase 
increased 

Renal and urinary 
disorders 

Uncommon renal impairment, blood in urine, bladder and urethral 
symptoms  

Rare nephropathy (including nephritis) 
Reproductive system and 
breast disorders 

Uncommon menstrual cycle and uterine bleeding disorders (including 
amenorrhea), breast disorders  

Rare sexual dysfunction  
General disorders and 
administration site 
conditions 

Common pyrexia, pain (any site), asthaenia, pruritus (any site), 
injection site reactions 

Uncommon chills, influenza-like illness, altered temperature 
perception, night sweats, flushing 

Rare fistula (any site) 
Investigations Uncommon blood alkaline phosphatase increased, coagulation time 

prolonged 
Rare blood uric acid increased 

Injury, poisoning and 
procedural complications 

Uncommon skin injuries, impaired healing 

*These events have been related to the class of TNF-antagonists, but incidence with certolizumab 
pegol is not known. 
**These events have been related to the class of TNF-antagonists. 



76 

 
The additional following adverse reactions have been observed uncommonly with Cimzia in other 
indications: gastrointestinal stenosis and obstructions, general physical health deterioration, abortion 
spontaneous and azoospermia. 
 
Description of selected adverse reactions 
 
Infections 
The incidence rate of new cases of infections in placebo-controlled clinical trials in rheumatoid 
arthritis was 1.03 per patient-year for all Cimzia-treated patients and 0.92 per patient-year for placebo-
treated patients. The infections consisted primarily of upper respiratory tract infections, urinary tract 
infections, and lower respiratory tract infections and herpes viral infections (see sections 4.3 and 4.4). 
 
In the placebo-controlled clinical trials in rheumatoid arthritis, there were more new cases of serious 
infection in the Cimzia treatment groups (0.07 per patient-year; all doses), compared with placebo 
(0.02 per patient-year). The most frequent serious infections included pneumonia, tuberculosis 
infections. Serious infections also included invasive opportunistic infections (e.g. pneumocystosis, 
fungal oesophagitis, nocardiosis and herpes zoster disseminated). There is no evidence of an increased 
risk of infections with continued exposure over time (see section 4.4). 
 
The incidence rate of new cases of infections in placebo-controlled clinical trials in psoriasis 
was 1.37 per patient-year for all Cimzia-treated patients and 1.59 per patient-year for placebo-treated 
patients. The infections consisted primarily of upper respiratory tract infections and viral infections 
(including herpes infections). The incidence of serious infections was 0.02 per patient-year in Cimzia 
treated patients. No serious infections were reported in the placebo-treated patients. There is no 
evidence of an increased risk of infections with continued exposure over time. 
 
Malignancies and lymphoproliferative disorders 
Excluding non-melanoma of the skin, 121 malignancies including 5 cases of lymphoma were observed 
in the Cimzia RA clinical trials in which a total of 4,049 patients were treated, representing 9,277 
patient-years. Cases of lymphoma occurred at an incidence rate of 0.05 per 100 patient-years and 
melanoma at an incidence rate of 0.08 per 100 patient-years with Cimzia in rheumatoid arthritis 
clinical trials (see section 4.4). One case of lymphoma was also observed in the Phase III psoriatic 
arthritis clinical trial. 
 
Excluding non-melanoma skin cancer, 11 malignancies including 1 case of lymphoma were observed 
in the Cimzia psoriasis clinical trials in which a total of 1112 patients were treated, representing 2300 
patient-years. 
 
Autoimmunity 
In the rheumatoid arthritis pivotal studies, for subjects who were ANA negative at baseline, 16.7% of 
those treated with Cimzia developed positive ANA titers, compared with 12.0% of subjects in the 
placebo group. For subjects who were anti-dsDNA antibody negative at baseline, 2.2% of those treated 
with Cimzia developed positive anti-dsDNA antibody titers, compared with 1.0% of subjects in the 
placebo group. In both placebo-controlled and open-label follow-up clinical trials for rheumatoid 
arthritis, cases of lupus-like syndrome were reported uncommonly. There have been rare reports of 
other immune-mediated conditions; the causal relationship to Cimzia is not known. The impact of 
long-term treatment with Cimzia on the development of autoimmune diseases is unknown. 
 
Injection site reactions 
In the placebo-controlled rheumatoid arthritis clinical trials, 5.8% of patients treated with Cimzia 
developed injection site reactions such as erythema, itching, haematoma, pain, swelling or bruising, 
compared to 4.8% of patients receiving placebo. Injection site pain was observed in 1.5% of patients 
treated with Cimzia with no cases leading to withdrawal. 
 



77 

Creatine phosphokinase elevations 
The frequency of creatine phosphokinase (CPK) elevations was generally higher in patients with 
axSpA as compared to the RA population. The frequency was increased both in patients treated with 
placebo (2.8% vs 0.4% in axSpA and RA populations, respectively) as well as in patients treated with 
Cimzia (4.7% vs 0.8% in axSpA and RA populations, respectively). The CPK elevations in the axSpA 
study were mostly mild to moderate, transient in nature and of unknown clinical significance with no 
cases leading to withdrawal. 
 
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. Multiple doses of up to 800 mg 
subcutaneously and 20 mg/kg intravenously have been administered. In cases of overdose, it is 
recommended that patients are monitored closely for any adverse reactions or effect, and appropriate 
symptomatic treatment initiated immediately. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: immunosuppressants, tumour necrosis factor alpha (TNFα) inhibitors, 
ATC code: L04AB05 
 
Mechanism of action 
 
Cimzia has a high affinity for human TNFα and binds with a dissociation constant (KD) of 90 pM. 
TNFα is a key pro-inflammatory cytokine with a central role in inflammatory processes. Cimzia 
selectively neutralises TNFα (IC90 of 4 ng/ml for inhibition of human TNFα in the in vitro 
L929 murine fibrosarcoma cytotoxicity assay) but does not neutralise lymphotoxin α (TNFβ).  
 
Cimzia was shown to neutralise membrane associated and soluble human TNFα in a dose-dependent 
manner. Incubation of monocytes with Cimzia resulted in a dose-dependent inhibition of 
lipopolysaccharide (LPS)-induced TNFα and IL1β production in human monocytes. 
 
Cimzia does not contain a fragment crystallisable (Fc) region, which is normally present in a complete 
antibody, and therefore does not fix complement or cause antibody-dependent cell-mediated 
cytotoxicity in vitro. It does not induce apoptosis in vitro in human peripheral blood-derived 
monocytes or lymphocytes, or neutrophil degranulation. 
 
Clinical efficacy 
 
Rheumatoid arthritis 
The efficacy and safety of Cimzia have been assessed in 2 randomised, placebo-controlled, double-
blind clinical trials in patients ≥ 18 years of age with active rheumatoid arthritis diagnosed according 
to American College of Rheumatology (ACR) criteria, RA-I (RAPID 1) and RA-II (RAPID 2). 
Patients had ≥ 9 swollen and tender joints each and had active RA for at least 6 months prior to 
baseline. Cimzia was administered subcutaneously in combination with oral MTX for a minimum 
of 6 months with stable doses of at least 10 mg weekly for 2 months in both trials. There is no 
experience with Cimzia in combination with DMARDs other than MTX. 
 



78 

The efficacy and safety of Cimzia was assessed in DMARD-naïve adult patients with active RA in a 
randomized, placebo-controlled, double-blind clinical trial (C-EARLY). In the C-EARLY trial patients 
were ≥ 18 years of age and had ≥ 4 swollen and tender joints each and must have been diagnosed with 
moderate to severe active and progressive RA within 1 year (as defined by the 2010 ACR/European 
League Against Rheumatism (EULAR) classification criteria). Patients had a mean time since 
diagnosis at baseline of 2.9 months and were DMARD naïve (including MTX). For both the Cimzia 
and placebo arms, MTX was initiated as of Week 0 (10 mg/week), titrated up to maximum tolerated 
dose by Week 8 (min 15 mg/week, max 25 mg/week allowed), and maintained throughout the study 
(average dose of MTX after Week 8 for placebo and Cimzia was 22.3 mg/week and 21.1 mg/week 
respectively). 
 
Table 2 Clinical trial description 

Study 
number 

Patient 
numbers 

Active dose regimen Study objectives 
 

RA-I 
(52 weeks) 

982 400 mg (0,2,4 weeks) 
with MTX 

200 mg or 400 mg 
every 2 weeks with MTX 

Evaluation for treatment of signs and 
symptoms and inhibition of structural damage.  
Co-primary endpoints: ACR 20 at Week 24 and 

change from baseline in mTSS at Week 52 
RA-II 

(24 weeks) 
619 400 mg (0,2,4 weeks) 

with MTX 
200 mg or 400 mg 
every 2 weeks with 

MTX 

Evaluation for treatment of signs and 
symptoms and inhibition of structural damage. 

Primary endpoint: ACR 20 at Week 24.  

C-EARLY 
(to 52 wee

ks) 

879 400 mg (0,2,4 weeks) 
with MTX 

200 mg every 2 weeks 
with MTX 

Evaluation for treatment of signs and 
symptoms and inhibition of structural damage 

in DMARD naïve patients.  
Primary endpoint: proportion of subjects in 

sustained remission* at Week 52 
mTSS: modified Total Sharp Score 
*Sustained remission at Week 52 is defined as DAS28[ESR] <2.6 at both Week 40 and Week 52. 
 
Signs and symptoms 
The results of clinical trials RA-I and RA-II are shown in Table 3. Statistically significantly greater 
ACR 20 and ACR 50 responses were achieved from Week 1 and Week 2, respectively, in both clinical 
trials compared to placebo. Responses were maintained through Weeks 52 (RA-I) and 24 (RA-II). Of 
the 783 patients initially randomised to active treatment in RA-I, 508 completed 52 weeks of placebo-
controlled treatment and entered the open-label extension study. Of these, 427 completed 2 years of 
open-label follow-up and thus had a total exposure to Cimzia of 148 weeks overall. The observed 
ACR 20 response rate at this timepoint was 91%.The reduction (RA-I) from Baseline in DAS28 (ESR) 
also was significantly greater (p<0.001) at Week 52 (RA-I) and Week 24 (RA-II) compared to placebo 
and maintained through 2 years in the open-label extension trial to RA-I. 
 
Table 3 ACR response in clinical trials RA-I and RA-II 

 Study RA-I 
Methotrexate combination 

(24 and 52 weeks) 

Study RA-II 
Methotrexate combination 

(24 weeks) 
Response Placebo + MTX 

 
N=199 

Cimzia  
200 mg + MTX 
every 2 weeks 

 
N=393 

Placebo + MTX 
 

N=127 

Cimzia  
200 mg + MTX 
every 2 weeks 

 
N=246 

ACR 20     
Week 24 14% 59%** 9% 57%** 
Week 52 13% 53%** N/A N/A 
ACR 50     
Week 24 8% 37%** 3% 33%** 
Week 52 8% 38%** N/A N/A 



79 

ACR 70     
Week 24 3% 21%** 1% 16%* 
Week 52 4% 21%** N/A N/A 
Major 
Clinical 
Responsea. 

1% 13%**   

Cimzia vs. placebo: *p≤0.01, ** p<0.001 
a. Major clinical response is defined as achieving ACR 70 response at every assessment over a 
continuous 6-month period 
Wald p-values are quoted for the comparison of treatments using logistic regression with factors for 
treatment and region. 
Percentage response based upon number of subjects contributing data (n) to that endpoint and time 
point which may differ from N 

 
The C-EARLY trial met its primary and key secondary endpoints. The key results from the study are 
presented in table 4.  
 
Table 4: C-EARLY trial: percent of patients in sustained remission and sustained low disease 

activity at Week 52 
Response Placebo+MTX 

N= 213 
Cimzia 200 mg + MTX 

N= 655 
Sustained remission* 
(DAS28(ESR) <2.6 at both Week 40 and 
Week 52) 

15.0 % 28.9%** 

Sustained low disease activity 
(DAS28(ESR) ≤3.2 at both Week 40 and 
Week 52) 

28.6 % 43.8%** 

*Primary endpoint of C-EARLY trial (to Week 52) 
Full analysis set, non-responder imputation for missing values. 
**Cimzia+MTX vs placebo+MTX: p<0.001 
p value was estimated from a logistic regression model with factors for treatment, region, and time 
since RA diagnosis at Baseline (≤4 months vs >4 months) 

 
Patients in the Cimzia+MTX group had a greater reduction from baseline in DAS 28 (ESR) compared 
with the placebo+MTX group observed as early as Week 2 and continued through 
Week 52 (p<0.001 at each visit). Assessments on remission (DAS28(ESR) <2.6), Low Disease 
Activity (DAS28(ESR) ≤3.2) status, ACR50 and ACR 70 by visit demonstrated that Cimzia+MTX 
treatment led to faster and greater responses than PBO+MTX treatment. These results were maintained 
over 52 weeks of treatment in DMARD-naïve subjects.  
 
Radiographic response 
In RA-I, structural joint damage was assessed radiographically and expressed as change in mTSS and 
its components, the erosion score and joint space narrowing (JSN) score, at Week 52, compared to 
baseline. Cimzia patients demonstrated significantly less radiographic progression than patients 
receiving placebo at Week 24 and Week 52 (see Table 5). In the placebo group, 52% of patients 
experienced no radiographic progression (mTSS ≤ 0.0) at Week 52 compared to 69% in the 
Cimzia 200 mg treatment group. 
 



80 

Table 5 Changes over 12 months in RA-I 
 Placebo + MTX 

N=199 
Mean (SD) 

Cimzia 200 mg + MTX 
N=393 

Mean (SD) 

Cimzia 200 mg + MTX – 
Placebo + MTX 
Mean Difference 

mTSS    
Week 52 2.8 (7.8) 0.4 (5.7) -2.4 
Erosion Score    
Week 52 1.5 (4.3) 0.1 (2.5) -1.4 
JSN Score    
Week 52 1.4 (5.0) 0.4 (4.2) -1.0 
p-values were < 0.001 for both mTSS and erosion score and ≤ 0.01 for JSN score. An ANCOVA 
was fitted to the ranked change from baseline for each measure with region and treatment as factors 
and rank baseline as a covariate. 

 
Of the 783 patients initially randomised to active treatment in RA-I, 508 completed 52 weeks of 
placebo-controlled treatment and entered the open-label extension study. Sustained inhibition of 
progression of structural damage was demonstrated in a subset of 449 of these patients who completed 
at least 2 years of treatment with Cimzia (RA-I and open-label extension study) and had evaluable data 
at the 2-year timepoint. 
 
In C-EARLY, Cimzia+ MTX inhibited the radiographic progression compared to placebo+MTX at 
Week 52 (see Table 6). In the placebo+MTX group, 49.7% of patients experienced no radiographic 
progression (change in mTSS ≤0.5) at Week 52 compared to 70.3% in the Cimzia+MTX group 
(p<0.001). 
 
Table 6 Radiographic change at Week 52 in trial C-EARLY 

 Placebo +MTX 
N= 163 

Mean (SD) 

Cimzia 200 mg + MTX 
N = 528 

Mean (SD) 

Cimzia 200 mg + MTX – 
Placebo +MTX 

Difference* 
mTSS 
Week 52 

1.8 (4.3) 0.2 (3.2)** -0.978 (-1.005, -0.500) 

Erosion score 
Week 52 

1.1 (3.0) 0.1 (2.1)** -0.500 (-0.508, -0.366) 

JSN score 
Week 52 

0.7 (2.3) 0.1 (1.7)** 0.000 (0.000, 0.000) 

Radiographic set with linear extrapolation. 
* Hodges-Lehmann point estimate of shift and 95% asymptotic (Moses) confidence interval. 
**Cimzia+MTX vs placebo+MTX p<0.001. p value was estimated from an ANCOVA model on the 
ranks with treatment, region, time since RA diagnosis at Baseline (≤4 months vs >4 months) as 
factors and Baseline rank as a covariate. 

 
Physical function response and health-related outcomes 
In RA-I and RA-II, Cimzia-treated patients reported significant improvements in physical function as 
assessed by the Health Assessment Questionnaire – Disability Index (HAQ-DI) and in tiredness 
(fatigue) as reported by the Fatigue Assessment Scale (FAS) from Week 1 through to the end of the 
studies compared to placebo. In both clinical trials, Cimzia-treated patients reported significantly 
greater improvements in the SF-36 Physical and Mental Component Summaries and all domain scores. 
Improvements in physical function and HRQoL were maintained through 2 years in the open-label 
extension to RA-I. Cimzia-treated patients reported statistically significant improvements in the Work 
Productivity Survey compared to placebo. 
 
In C-EARLY, Cimzia+MTX-treated patients reported significant improvements at Week 52 compared 
to placebo+MTX in pain as assessed by the Patient Assessment of Arthritis Pain (PAAP) – 48,5 vs 
- 44,0 (least square mean) (p<0.05). 
 



81 

DoseFlex clinical trial 
The efficacy and safety of 2 dose regimens (200 mg every 2 weeks and 400 mg every 4 weeks) of 
Cimzia versus placebo were assessed in an 18-week, open-label, run-in, and 16-week randomised, 
double-blind, placebo-controlled clinical trial in adult patients with active rheumatoid arthritis 
diagnosed according to the ACR criteria who had inadequate response to MTX. 
 
Patients received loading doses of Cimzia 400 mg at weeks 0, 2, and 4 followed by Cimzia 200 mg 
every 2 weeks during the initial open label period. Responders (achieved ACR 20) at week 16 were 
randomised at week 18 to Cimzia 200 mg every 2 weeks, Cimzia 400 mg every 4 weeks, or placebo in 
combination with MTX for an additional 16 weeks (total trial length: 34 weeks). These 3 groups were 
well balanced with regards to clinical response following the active run-in period (ACR 20: 83-84% at 
week 18). 
 
The primary endpoint of the study was the ACR 20 responder rate at week 34. The results at 
week 34 are shown in Table 7. Both Cimzia regimens showed sustained clinical response and were 
statistically significant compared to placebo at week 34. The ACR 20 endpoint was achieved for both 
Cimzia 200 mg every 2 weeks and 400 mg every 4 weeks. 
 
Table 7 ACR response in DoseFlex clinical trial at week 34 

Treatment regimen week 0 to 16 Cimzia 400 mg + MTX at week 0, 2 and 4, followed by 
Cimzia 200 mg + MTX every 2 weeks  

Randomised, double-blind 
treatment regimen 
week 18 to 34 
 

Placebo + MTX 
 
 

N=69 

Cimzia  
200 mg + MTX 
every 2 weeks 

N=70 

Cimzia  
400 mg + MTX 
every 4 weeks 

N=69 
ACR 20 
p-value* 

45% 
N/A 

67% 
0.009 

65% 
0.017 

ACR 50 
p-value* 

30% 
N/A 

50% 
0.020 

52% 
0.010 

ACR 70 
p-value* 

16% 
N/A 

30% 
0.052 

38% 
0.005 

N/A: Not Applicable 
*Wald p-values for Cimzia 200 mg vs. placebo and Cimzia 400 mg vs. placebo comparisons are 
estimated from a logistic regression model with factors for treatment 

 
Axial spondyloarthritis (non-radiographic axial spondyloarthritis and ankylosing spondylitis 
subpopulations) 
AS001 
The efficacy and safety of Cimzia were assessed in one multicenter, randomized, double-blind, 
placebo-controlled trial (AS001) in 325 patients ≥18 years of age with adult-onset active axial 
spondyloarthritis for at least 3 months as defined by the Assessment of Spondyloarthritis International 
Society (ASAS) Classification Criteria for axial spondyloarthritis. The axial spondyloarthritis overall 
population included subpopulations with and without (non-radiographic axial spondyloarthritis [nr-
axSpA]) radiographic evidence for ankylosing spondylitis (AS) (also known as radiographic axial 
spondyloarthritis). Patients had active disease as defined by the Bath Ankylosing Spondylitis Disease 
Activity Index (BASDAI) ≥ 4, spinal pain ≥ 4 on a 0 to 10 Numerical Rating Scale (NRS) and 
increased CRP or current evidence of sacroiliitis on Magnetic Resonance Imaging (MRI). Patients 
must have been intolerant to or had an inadequate response to at least one NSAID. Overall, 16% of 
patients had prior TNF-antagonist exposure. Patients were treated with a loading dose of 
Cimzia 400 mg at Weeks 0, 2 and 4 (for both treatment arms) or placebo followed by either 200 mg of 
Cimzia every 2 weeks or 400 mg of Cimzia every 4 weeks or placebo. 87.7% of patients received 
concomitant NSAIDs. The primary efficacy endpoint was the ASAS20 response rate at Week 12. 
The 24-week double-blind, placebo-controlled treatment period of the study was followed by a 24-
week dose-blind treatment period, and a 156-week open-label treatment period. The maximum 
duration of the study was 204 weeks. All patients received Cimzia in both the dose-blind and open-



82 

label follow-up periods. A total of 199 subjects (61.2% of randomized subjects) completed the study 
through Week 204.  
 
Key efficacy outcomes 
In AS001 clinical trial, at Week 12 ASAS20 responses were achieved by 58% of patients receiving 
Cimzia 200 mg every 2 weeks and 64% of patients receiving Cimzia 400 mg every 4 weeks as 
compared to 38% of patients receiving placebo (p<0.01). In the overall population, the percentage of 
ASAS20 responders was clinically relevant and significantly higher for the Cimzia 200 mg 
every 2 weeks and Cimzia 400 mg every 4 weeks treatment groups compared to placebo group at 
every visit from Week 1 through Week 24 (p≤0.001 at each visit). At Weeks 12 and 24, the percentage 
of subjects with an ASAS40 response was greater in the Cimzia-treated groups compared to placebo.  
 
Similar results were achieved in both the ankylosing spondylitis and non-radiographic axial 
spondyloarthritis subpopulations. In women, ASAS20 responses were not statistically significantly 
different from placebo until after the Week 12 time point. 
 
Improvements in ASAS5/6, Partial Remission and BASDAI-50 were statistically signficant at 
Week 12 and Week 24 and were sustained up to Week 48 in the overall popualtion as well as in the 
subpopulations. Key efficacy outcomes from the AS001 clinical trial are shown in Table -8.  
 
Among patients remaining in the study, improvements in all afore-mentioned key efficacy outcomes 
were maintained through Week 204 in the overall population as well as in the subpopulations. 
 
Table 8 Key efficacy outcomes in AS001 clinical trial (percent of patients) 

 
 

Parameters 

Ankylosing spondylitis Non-radiographic 
axial 

spondyloarthritits 

 Axial 
spondyloarthritis 

Overall Population 
 Placebo 

N=57 
Cimzia 

all dosing 
regimens(a) 

N=121 

Placebo 
N=50 

Cimzia all 
dosing 

regimens(a) 
N=97 

Placebo 
N=107 

 

Cimzia all 
dosing 

regimens(a) 
N=218 

ASAS20(b,c) 
Week 12 
Week 24 

 
37% 
33% 

 
60%* 

69%** 

 
40% 
24% 

 
61%* 

68%** 

 
38% 
29% 

 
61%** 
68%** 

ASAS40(c,d) 
Week 12 
Week 24 

 
19% 
16% 

 
45%** 
53%** 

 
16% 
14% 

 
47%** 
51%** 

 
18% 
15% 

 
46%** 
52%** 

ASAS 5/6(c,d) 
Week 12 
Week 24 

 
9% 
5% 

 
42%** 
40%** 

 
8% 
4% 

 
44%** 
45%** 

 
8% 
5% 

 
43%** 
42%** 

Partial remission(c,d) 
Week 12 
Week 24 

 
2% 
7% 

 
20%** 
28%** 

 
6% 
10% 

 
29%** 
33%** 

 
4% 
9% 

 
24%** 
30%** 

BASDAI 50(c,d) 
Week 12 
Week 24 

 
11% 
16% 

 
41%** 
49%** 

 
16% 
20% 

 
49%** 
57%** 

 
13% 
18% 

 
45%** 
52%** 

(a) Cimzia all dosing regimen = data from Cimzia 200 mg administered every 2 weeks preceded by a 
loading dose of 400 mg at Weeks 0, 2 and 4 plus Cimzia 400 mg administered every 4 weeks preceded 
by a loading dose of 400 mg at Weeks 0, 2 and 4 
(b) Results are from the randomized set 
(c) Wald p-values are quoted for the comparison of treatments using logistic regression with factors for 
treatment and region.  
(d) Full Analysis Set  
NA = not available 
*p≤0.05, Cimzia vs placebo 
**p<0.001, Cimzia vs placebo 



83 

 
Spinal mobility 
Spinal mobility was assessed in the double-blind, placebo-controlled period by using BASMI at 
several time points including Baseline, Week 12 and Week 24. Clinically meaningful and statistically 
significant differences in Cimzia-treated patients compared with placebo-treated patients were 
demonstrated at each post-baseline visit. The difference from placebo tended to be greater in nr-axSpA 
than in the AS subpopulation which may be due to less chronic structural damage in nr-axSpA 
patients.  
The improvement in BASMI linear score achieved at Week 24 was maintained through Week 204 for 
patients who remained in the study. 
 
Physical function response and health-related outcomes  
In the AS001 clinical trial, Cimzia-treated patients reported significant improvements in physical 
function as assessed by the BASFI and in pain as assessed by the Total and Nocturnal Back Pain NRS 
scales as compared to placebo. Cimzia-treated patients reported significant improvements in tiredness 
(fatigue) as reported by the BASDAI-fatigue item and in health-related quality of life as measured by 
the ankylosing spondylitis QoL (ASQoL) and the SF-36 Physical and Mental Component Summaries 
and all domain scores as compared to placebo. Cimzia-treated patients reported significant 
improvements in axial spondyloarthritis-related productivity at work and within household, as reported 
by the Work Productivity Survey as compared to placebo. For patients remaining in the study, 
improvements in all afore-mentioned outcomes were largely maintained through Week 204. 
 
Inhibition of inflammation in Magnetic Resonance Imaging (MRI) 
In an imaging sub-study including 153 patients, signs of inflammation were assessed by MRI at 
week 12 and expressed as change from baseline in SPARCC (Spondyloarthritis Research Consortium 
of Canada) score for sacroiliac joints and ASspiMRI-a score in the Berlin modifications for the spine. 
At week 12, significant inhibition of inflammatory signs in both sacroiliac joints and the spine was 
observed in the Cimzia-treated patients (all dose group), in the overall axial spondyloarthritis 
population as well as in the sub-populations of ankylosing spondylitis and non-radiographic axial 
spondyloarthritis. 
Among patients remaining in the study, who had both baseline values and week 204 values, inhibition 
of inflammatory signs in both the sacroiliac joints (n=72) and spine (n=82) was largely maintained 
through Week 204 in the overall axial spondyloarthritis population as well as in both the AS and the 
nr-axSpA subpopulations. 
 

C-OPTIMISE 

The efficacy and safety of dose reduction and treatment withdrawal in patients in sustained remission 
were assessed in adult patients (18-45 years of age) with early active axSpA (symptom duration of less 
than 5 years), an ASDAS score ≥2.1 (and similar disease inclusion criteria as in the AS001 study), and 
who had inadequate response to at least 2 NSAIDs or an intolerance to or contraindication for 
NSAIDs. Patients included both the AS and nr-axSpA subpopulations of axSpA, and were enrolled 
into an open-label run-in 48-Week period (Part A) during which they all received 3 loading doses of 
Cimzia 400 mg at Weeks 0, 2, and 4 followed by Cimzia 200 mg every 2 weeks from Week 6 to Week 
46.   

Patients who achieved sustained remission (defined as having inactive disease [ASDAS<1.3] over a 
period of at least 12 weeks) and remained in remission at week 48, were randomized into Part B and 
received either Cimzia 200 mg every 2 weeks (N=104), Cimzia 200 mg every 4 weeks (dose 
reduction, N=105), or placebo (treatment withdrawal, N=104) for 48 Weeks.  

The primary efficacy variable was the percentage of patients who did not experience a flare during 
Part B. 

Patients who experienced a flare in Part B, ie, had an ASDAS ≥2.1 at 2 consecutive visits or 
ASDAS >3.5 at any visit during Part B, received escape treatment of Cimzia 200 mg every 2 weeks 



84 

for at least 12 weeks (with a loading dose of Cimzia 400 mg at Week 0, 2 and 4 in placebo-treated 
patients).  

Clinical response 

The percentage of patients who achieved sustained remission at Week 48 in Part A was 43.9% for the 
overall axSpA population, and was similar in the nr-axSpA (45.3%) and AS (42.8%) subpopulations. 

Among the patients who were randomized in Part B (N=313), a statistically significant (p <0.001, 
NRI) greater proportion of patients did not experience a flare when continuing treatment with 
Cimzia 200 mg every 2 weeks (83.7%) or Cimzia 200 mg every 4 weeks (79.0%) compared with 
treatment withdrawal (20.2%).   

The difference in time to flare between the treatment withdrawal group and either of the Cimzia 
treatment groups, was statistically significant (p<0.001 for each comparison) and clinically 
meaningful. In the placebo group, flares started approximately 8 weeks after Cimzia was withdrawn, 
with the majority of flares occurring within 24 weeks of treatment withdrawal (Figure 1).  

Figure 1  Kaplan-Meier curve of time to flare 

 
Non responder imputation (NRI) was used; Results are for the Randomized Set 
Note: Time to flare was defined as the time from the date of randomization to the date of the flare. For study participants who did not have a  
flare, the time to flare was censored at the date of Week 96 Visit. 
The Kaplan-Meier plot was truncated to 97 weeks when <5% of participants were still remaining in the study. 
 

Results for Part B are presented in Table 9. 

 



85 

Table 9  Maintenance of clinical response in Part B at Week 96  

Endpoints 

Placebo 
(treatment 

withdrawal) 
N=104 

CIMZIA 200 mg 
every 2 weeks 

N=104 

CIMZIA 200 mg  

every 4 weeks 
N=105 

ASDAS-MI, n (%)1  
Part B Baseline (Week 48) 84 (80.8) 90 (86.5) 89 (84.8) 

Week 96 11 (10.6) 70 (67.3)* 61 (58.1)* 

ASAS40, n (%)1  

Part B Baseline (Week 48) 101 (97.1) 103 (99.0) 101 (96.2) 

Week 96 22 (21.2) 88 (84.6)* 77 (73.3)* 

BASDAI change from Part B 
baseline (Week 48), LS mean (SE)2  

Week 96 3.02 (0.226) 0.56 (0.176)* 0.78 (0.176)* 

ASDAS change from Part B 
baseline (Week 48), LS mean (SE)2  

Week 96 1.66 (0.110) 0.24 (0.077)* 0.45 (0.077)* 
1 Non responder imputation (NRI) was used; Results are for the Randomized Set 
2 mixed model with repeated measures (MMRM) was used; Results are for the Randomized Set 
ASDAS-MI = Ankylosing Spondylitis Disease Activity Score-Major Improvement; ASAS: Assessment of Sponyloarthritis international 
Society; ASAS40= ASAS40% response criteria; SE = Standard error;  
Note: ASDAS major improvement is defined as a reduction from Baseline ≥2.0.  
Note: Part A Baseline was used as a reference to define ASDAS clinical improvement variables and ASAS variables  
* Nominal p<0.001, CIMZIA vs. placebo 

 

Inhibition of inflammation in Magnetic Resonance imaging (MRI) 
In Part B, signs of inflammation were assessed by MRI at Week 48 and at Week 96 and expressed as 
change from baseline in SIJ SPARCC and ASspiMRI-a score in the Berlin modifications. Patients who 
were in sustained remission at Week 48 had no or very low inflammation, and no meaningful increase 
in inflammation was observed at Week 96 irrespective of their treatment group. 
 
Retreatment in patients that experience a flare 
In Part B, 70% (73/104) placebo-treated patients, 14% (15/105) patients treated with Cimzia 200 mg 
every 4 weeks and 6.7% (7/104) patients treated with Cimzia 200 mg every 2 weeks experienced a flare 
and were subsequently treated with Cimzia 200 mg every 2 weeks.  
Among the 15 patients who flared in the group allocated to Cimzia 200 mg every 4 weeks, all patients 
completed 12 weeks of rescue therapy with Cimzia and had available ASDAS data, out of which 12 
(80%) had ASDAS Low or Inactive disease (i.e. all ASDAS <2.1) after 12 weeks of restarting the open-
label treatment. 
Among the 73 patients who flared in the group allocated to treatment withdrawal, 71 patients completed 
12 weeks of rescue therapy with Cimzia and had available ASDAS data, out of which 64 (90%) had 
ASDAS Low or Inactive disease (i.e. all ASDAS < 2.1) after 12 weeks of restarting the open-label 
treatment. 
Based on the results from C-OPTIMISE, a dose reduction in patients in sustained remission after one 
year of treatment with Cimzia may be considered (see section 4.2). Withdrawal of Cimzia treatment is 
associated with a high risk of flare. 
 
Non-radiographic axial spondyloarthritis (nr-axSpA) 
The efficacy and safety of Cimzia were assessed in a 52 weeks multicenter, randomized, double-blind, 
placebo-controlled study (AS0006) in 317 patients ≥18 years of age with adult-onset axial 



86 

spondyloarthritis and back pain for at least 12 months. Patients had to fulfil ASAS criteria for nr- 
axSpA (not including family history and good response to NSAIDs), and have had objective signs of 
inflammation indicated by C-reactive protein (CRP) levels above the upper limit of normal and/or 
sacroiliitis on magnetic resonance imaging (MRI), indicative of inflammatory disease [positive CRP 
(> ULN) and/or positive MRI], but without definitive radiographic evidence of structural damage on 
sacroiliac joints. Patients had active disease as defined by the BASDAI ≥4, and spinal pain ≥4 on 
a 0 to 10 NRS. Patients must have been intolerant to or had an inadequate response to at least two 
NSAIDs. Patients were treated with placebo or a loading dose of Cimzia 400 mg at 
Weeks 0, 2 and 4 followed by 200 mg of Cimzia every 2 weeks. Utilization and dose adjustment of 
standard of care medication (SC) (e.g., NSAIDs, DMARDs, corticosteroids, analgesics) were 
permitted at any time. The primary efficacy variable was the Ankylosing Spondylitis Disease Activity 
Score major improvement (ASDAS-MI) response at Week 52. ASDAS-MI response was defined as an 
ASDAS reduction (improvement) ≥ 2.0 relative to baseline or as reaching the lowest possible score. 
ASAS 40 was a secondary endpoint.  
At baseline, 37 % and 41% of patients had high disease activity (ASDAS ≥2.1, ≤3.5) and 62% and 
58% of patient had very high disease activity (ASDAS >3.5) in the CIMZIA group and placebo group 
respectively.  
 
Clinical response 
Study AS0006, performed in subjects without radiographic signs of inflammation in the SI joints, 
confirmed the effect previously demonstrated in this subgroup in the AS001 study.  
At Week 52, a statistically significant greater proportion of patients treated with Cimzia achieved 
ASDAS-MI response compared to patients treated with placebo. Cimzia-treated patients also had 
improvements compared to placebo in multiple components of axial spondyloarthritis disease activity, 
including CRP. At both Week 12 and 52, ASAS 40 responses were significantly greater than placebo. 
Key results are presented in Table 10. 
 
Table 10: ASDAS-MI and ASAS 40 responses in AS0006 (percent of patients) 

 

Parameters Placebo N= 158 
Cimziaa 200 mg every 2 weeks 
N= 159 

ASDAS-MI  
Week 52 

 
7% 
 

 
47%* 

ASAS 40 
Week 12 
 
Week 52 

 
11% 
 
16% 

 
48%* 
 
57%* 

a Cimzia administered every 2 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4 
* p<0.001 
All percents reflect the proportion of patients who responded in the full analysis set.  

 
At Week 52, the percentage of patients achieving ASDAS inactive disease (ASDAS < 1.3) was 36.4 % 
for the Cimzia group compared to 11.8 % for the placebo group. 

 
At Week 52, patients treated with Cimzia showed a clinical meaningful improvement in the MASES 
compared to placebo (LS mean change from baseline -2.4 ; -0.2 respectively).  
 
Psoriatic arthritis 
The efficacy and safety of Cimzia were assessed in a multicentre, randomised, double-blind, placebo 
controlled clinical trial (PsA001) in 409 patients ≥ 18 years of age with adult-onset active psoriatic 
arthritis for at least 6 months as defined by the Classification Criteria for Psoriatic Arthritis 
(CASPAR) criteria. Patients had ≥ 3 swollen and tender joints and increased acute phase reactants. 
Patients also had active psoriatic skin lesions or a documented history of psoriasis and had failed 1 or 
more DMARDs. Previous treatment with one TNF-antagonist was allowed and 20% of patients had 
prior TNF-antagonist exposure. Patients received a loading dose of Cimzia 400 mg at 



87 

Weeks 0, 2 and 4 (for both treatment arms) or placebo followed by either Cimzia 200 mg 
every 2 weeks or 400 mg every 4 weeks or placebo every 2 weeks. Patients receiving concomitant 
NSAIDs and conventional DMARDs were 72.6% and 70.2% respectively. The two primary endpoints 
were the percentage of patients achieving ACR 20 response at Week 12 and change from baseline in 
modified Total Sharp Score (mTSS) at Week 24. Efficacy and safety of Cimzia in patients with PsA 
whose predominant symptoms were sacroiliitis or axial spondyloarthritis have not been separately 
analysed. 
The 24-week double-blind placebo controlled treatment period of the study was followed by a 24-
week dose-blind treatment period and an 168-week open-label treatment period. The maximum 
duration of the study was 216 weeks. All patients received Cimzia in both the dose-blind and open-
label follow-up periods. A total of 264 subjects (64.5%) completed the study through Week 216. 
 
ACR response 
Cimzia-treated patients had a statistically significant higher ACR 20 response rate at Week 12 and 
Week 24 compared with placebo-treated patients (p<0.001). The percentage of ACR 20 responders 
was clinically relevant for the Cimzia 200 mg every 2 weeks and Cimzia 400 mg every 4 weeks 
treatment groups compared to placebo group at every visit after baseline through Week 24 (nominal 
p≤0.001 at each visit). Cimzia treated patients also had significant improvements in 
ACR 50 and 70 response rates. At week 12 and 24 improvements in parameters of peripheral activity 
characteristic of psoriatic arthritis (e.g. number of swollen joints, number of painful/tender joints, 
dactylitis and enthesitis) were seen in the Cimzia-treated patients (nominal p-value p<0.01).  
Key efficacy outcomes from the PsA001 clinical trial are shown in Table 11. 
 
Table 11: Key efficacy outcomes in PsA001 clinical trial (percent of patients) 
Response Placebo 

 
N=136 

Cimzia(a)200 mg 
Q2W 
N=138 

Cimzia(b) 400 mg 
Q4W 
N=135 

ACR20 
Week 12 
Week 24 

 
24% 
24% 

 
58%** 
64%** 

 
52%** 
56%** 

ACR50 
Week 12 
Week 24 

 
11% 
13% 

 
36%** 
44%** 

 
33%** 
40%** 

ACR70 
Week 12 
Week 24 

 
3% 
4% 

 
25%** 
28%** 

 
13%* 
24%** 

Response Placebo 
 

N=86 

Cimzia(a)200 mg 
Q2W 
N=90 

Cimzia(b) 400 mg 
Q4W 
N=76 

PASI 75 (c) 
Week 12 
Week 24 
Week 48 

 
14% 
15% 
N/A 

 
47%*** 
62%*** 
67% 

 
47%*** 
61%*** 
62% 

(a) Cimzia administered every 2 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4 
(b) Cimzia administered every 4 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4 
(c) In subjects with at least 3% psoriasis BSA at Baseline 
*p<0.01, Cimzia vs placebo 
**p<0.001, Cimzia vs placebo  
***p<0.001(nominal), Cimzia vs placebo  
Results are from the randomized set.Treatment Difference: Cimzia 200 mg-placebo, Cimzia 400 mg-  
placebo (and corresponding 95% CI and p-value) are estimated using a standard two-sided Wald 
asymptotic standard errors test. Non-responder Imputation (NRI) is used for patients who escaped 
therapy or had missing data. 

 
Among 273 patients initially randomised to Cimzia 200 mg every 2 weeks and Cimzia 400 mg 
every 4 weeks, 237 (86.8%) were still on this treatment at Week 48. Of the 138 patients randomised to 



88 

Cimzia 200 mg every 2 weeks, 92, 68 and 48 had an ACR 20/50/70 response, at Week 48 respectively. 
Of the 135 patients randomised to Cimzia 400 mg every 4 weeks, 89, 62 and 41 patients had an 
ACR 20/50/70 response, respectively.  
Among patients remaining in the study, ACR 20, 50 and 70 response rates were maintained through 
Week 216. This was also the case for the other parameters of peripheral activity (e.g. number of 
swollen joints, number of painful/tender joints, dactylitis and enthesitis). 
 
Radiographic response 
In PsA001 clinical trial, inhibition of progression of structural damage was assessed radiographically 
and expressed as the change in modified total Sharp score (mTSS) and its components, the Erosion 
Score (ES) and Joint Space Narrowing score (JSN) at Week 24, compared to baseline. The mTSS 
Score was modified for psoriatic arthritis by addition of hand distal interphalangeal joints. Cimzia 
treatment inhibited the radiographic progression compared with placebo treatment at Week 24 as 
measured by change from baseline in total mTSS Score (LS mean [±SE] score was 0.28 [±0.07] in the 
placebo group compared with 0.06 [±0.06] in the Cimzia all doses group; p=0.007). Inhibition of 
radiographic progression was maintained with Cimzia treatment up to Week 48 in the subset of 
patients at higher risk of radiographic progression (patients with a Baseline mTSS score of > 6). 
Inhibition of radiographic progression was further maintained up to Week 216 for the patients who 
remained in the study. 
 
Physical function response and health-related outcomes 
In PsA001 clinical trial, Cimzia-treated patients reported significant improvements in physical 
function as assessed by the Health Assessment Questionnaire – Disability Index (HAQ-DI), in pain as 
assessed by the PAAP and in tiredness (fatigue) as reported by the Fatigue Assessment Scale (FAS) as 
compared to placebo. Cimzia-treated patients reported significant improvements in health-related 
quality of life as measured by the psoriatic arthritis QoL (PsAQoL) and the SF-36 Physical and Mental 
Components and in psoriatic arthritis-related productivity at work and within household, as reported 
by the Work Productivity Survey compared to placebo. Improvements in all afore-mentioned 
outcomes were maintained through Week 216. 
 
Plaque psoriasis 
The efficacy and safety of Cimzia were assessed in two placebo-controlled studies (CIMPASI-1 and 
CIMPASI-2) and one placebo- and active-controlled study (CIMPACT) in patients ≥18 years of age 
with moderate to severe chronic plaque psoriasis for at least 6 months. Patients had a Psoriasis Area 
and Severity Index (PASI) score ≥ 12, body surface area (BSA) involvement of ≥ 10%, Physician 
Global Assessment (PGA) of ≥ 3, and were candidates for systemic therapy and/or phototherapy 
and/or chemophototherapy. Patients who were ‘primary’ non-responders on any prior biologic therapy 
(defined as no response within the first 12 weeks of treatment) were excluded from the phase III 
studies (CIMPASI-1, CIMPASI-2 and CIMPACT). The efficacy and safety of Cimzia were evaluated 
versus etanercept in the CIMPACT study. 
 
In studies CIMPASI-1 and CIMPASI-2 the co-primary efficacy endpoints were the proportion of 
patients achieving PASI 75 and PGA “clear” or “almost clear” (with at least a 2-point reduction from 
baseline) at Week 16. In the CIMPACT study, the primary efficacy endpoint was the proportion of 
patients achieving PASI 75 at Week 12. PASI75 and PGA at Week 16 were key secondary endpoints. 
PASI 90 at Week 16 was a key secondary endpoint in all 3 studies.  
 
CIMPASI-1 and CIMPASI-2 evaluated 234 patients and 227 patients respectively. In both studies 
patients were randomized to receive placebo or Cimzia 200 mg every 2 weeks (following a loading 
dose of Cimzia 400 mg at Weeks 0, 2 and 4) or Cimzia 400 mg every 2 weeks. At week 16, patients 
randomized to Cimzia who achieved a PASI 50 response continued to receive Cimzia up to 
Week 48 at the same randomized dose. Patients originally randomized to placebo that achieved a 
PASI 50 response but not a PASI 75 response at Week 16 received Cimzia 200 mg every 2 weeks 
(with a loading dose of Cimzia 400 mg at Weeks 16, 18, and 20). Patients with an inadequate response 
at Week 16 (PASI 50 non-responders) were eligible to receive Cimzia 400 mg every 2 weeks in an 
open-label manner for a maximum of 128 weeks. 
 



89 

The CIMPACT study evaluated 559 patients. Patients were randomized to receive placebo, or 
Cimzia 200 mg every 2 weeks (following a loading dose of Cimzia 400 mg at Weeks 0, 2 and 4), or 
Cimzia 400 mg every 2 weeks up to Week 16, or etanercept 50 mg twice weekly, up to Week 12. 
Patients originally randomized to Cimzia who achieved a PASI75 response at Week 16 were re-
randomized based on their original dosing schedule. Patients on Cimzia 200 mg every 2 weeks were 
re-randomized to Cimzia 200 mg every 2 weeks, Cimzia 400 mg every 4 weeks or placebo. Patient on 
Cimzia 400 mg every 2 weeks were re-randomized to Cimzia 400 mg every 2 weeks, Cimzia 200 mg 
every 2 weeks, or placebo. Patients were evaluated in a double-blind placebo-controlled manner 
through Week 48. All subjects who did not achieve a PASI 75 response at Week 16 entered an escape 
arm and received Cimzia 400 mg every 2 weeks in an open-label manner for a maximum of 128 
weeks. 
 
In all three studies, the blinded 48-week maintenance period was followed by a 96-week open-label 
treatment period for the patients who were PASI 50 responders at Week 48. All these patients, 
including those receiving Cimzia 400 mg every 2 weeks, started the open-label period at Cimzia 200 
mg every 2 weeks. 
 
Patients were predominantly men (64%) and Caucasian (94%), with a mean age of 45.7 years 
(18 to 80 years); of these, 7.2% were ≥ 65 years of age. Of the 850 patients randomized to receive 
placebo or Cimzia in these placebo-controlled studies, 29% of patients were naïve to prior systemic 
therapy for the treatment of psoriasis. 47% had received prior phototherapy or chemophototherapy, 
and 30% had received prior biologic therapy for the treatment of psoriasis. Of the 850 patients, 14% 
had received at least one TNF-antagonist, 13% had received an anti-IL-17, and 5% had received an 
anti-IL 12/ 23. Eighteen percent of patients reported a history of psoriatic arthritis at baseline. The 
mean PASI score at baseline was 20 and ranged from 12 to 69. The baseline PGA score ranged from 
moderate (70%) to severe (30%). Mean baseline BSA was 25% and ranged from 10% to 96%. 
 
Clinical response at Week 16 and 48 
The key results of CIMPASI-1 and CIMPASI-2 studies are presented in Table 12. 
 
Table 12: Clinical response in studies CIMPASI-1 and CIMPASI-2 at Week 16 and Week 48 
 Week 16 Week 48 
CIMPASI-1 
 Placebo 

 
N=51 

Cimzia 200 mg 
Q2W a) 
N=95 

Cimzia 400 mg 
Q2W 
N=88 

Cimzia 200 mg 
Q2W 
N=95 

Cimzia 400 mg 
Q2W 
N=88 

PGA clear or 
almost clearb) 

4.2% 47.0%* 57.9%* 52.7% 69.5% 

PASI 75 6.5% 66.5%* 75.8%* 67.2% 87.1% 
PASI 90 0.4% 35.8%* 43.6%* 42.8% 60.2% 
CIMPASI-2 
 Placebo 

 
N=49 

Cimzia 200 mg 
Q2W a) 
N=91 

Cimzia 400 mg 
Q2W 
N=87 

Cimzia 200 mg 
Q2W 
N= 91 

Cimzia 400 mg 
Q2W 
N= 87 

PGA clear or 
almost clearb) 

2.0% 66.8%* 71.6%* 72.6% 66.6% 

PASI 75 11.6% 81.4%* 82.6%* 78.7% 81.3% 
PASI 90 4.5% 52.6%* 55.4%* 59.6% 62.0% 
a) Cimzia 200 mg administered every 2 weeks preceded by a loading dose of 400 mg at Week 0, 2, 4. 
b) PGA 5 category scale. Treatment success of “clear” (0) or “almost clear”(1) consisted of no signs of 
psoriasis or normal to pink coloration of lesions, no thickening of the plaque, and none to minimal 
focal scaling. 
* Cimzia vs placebo: p< 0.0001.  
Response rates and p-values for PASI and PGA were estimated based on a logistic regression model 
where missing data were imputed using multiple imputation based on the MCMC method. Subject 
who escaped or withdrew (based on not achieving PASI 50 response) were treated as non-responders 
at Week 48. 



90 

Results are from the Randomized Set. 
 
The key results of the CIMPACT trial are presented in Table 13. 
 
Table 13: Clinical response in CIMPACT study at Week 12 and Week 16 
 Week 12 Week 16 
 Placebo 

N=57 
Cimzia 
200 mg 
Q2W a) 
N=165 

Cimzia 
400 mg 
Q2W 

N=167 

Etanercept 
50 mg 
BiW 

N=170 

Placebo 
N=57 

Cimzia 
200 mg 
Q2W 

N=165 

Cimzia 
400 mg 
Q2W 

N=167 
PASI 75 5% 61.3%*,§ 66.7%*,§§ 53.3% 3.8% 68.2%* 74.7%* 
PASI 90 0.2% 31.2%* 34.0%* 27.1% 0.3% 39.8%* 49.1%* 
PGA clear 
or almost 
clear b) 

1.9% 39.8%** 50.3%* 39.2% 3.4% 48.3%* 58.4%* 

a) Cimzia 200 mg administered every 2 weeks preceded by a loading dose of 400 mg at Week 0, 2, 4. 
b) PGA 5 category scale. Treatment success of “clear” (0) or “almost clear”(1) consisted of no signs of 
psoriasis or normal to pink coloration of lesions, no thickening of the plaque, and none to minimal 
focal scaling. 
* Cimzia vs placebo: p< 0.0001.  
§ Cimzia 200 mg every 2 weeks versus etanercept 50 mg twice weekly demonstrated non-inferiority 
(difference between etanercept and Cimzia 200 mg every 2 weeks was 8.0%, 95% CI -2.9, 18.9, based 
on a pre-specified non-inferiority margin of 10%). 
§§ Cimzia 400 mg every 2 weeks versus etanercept 50 mg twice weekly demonstrated superiority 
(p<0.05) 
** Cimzia vs Placebo p< 0.001. Response rates and p-values based on a logistic regression model.  
Missing data were imputed using multiple imputation based on the MCMC method. Results are from 
the Randomized Set. 
 
In all 3 studies, the PASI 75 response rate was significantly greater for Cimzia compared to placebo 
starting at Week 4. 
 
Both doses of Cimzia demonstrated efficacy compared to placebo regardless of age, gender, body 
weight, BMI, psoriasis disease duration, previous treatment with systemic therapies and previous 
treatment with biologics.  
 
Maintenance of response  
In an integrated analysis of  CIMPASI-1 and CIMPASI-2, among patients who were PASI 75 
responders at Week 16 and received Cimzia 400 mg every 2 weeks (N=134 of 175 randomised 
subjects) or Cimzia 200 mg every 2 weeks (N=132 of 186 randomised subjects), the maintenance of 
response at Week 48 was 98.0% and 87.5%, respectively. Among patients who were PGA clear or 
almost clear at Week 16 and received Cimzia 400 mg every 2 weeks (N=103 of 175) or Cimzia 200 
mg every 2 weeks (N=95 of 186), the maintenance of response at Week 48 was 85.9% and 84.3% 
respectively. 
 
After an additional 96 weeks of open-label treatment (Week 144) the maintenance of response was 
evaluated. Twenty-one percent of all randomised subjects were lost to follow-up before Week 144. 
Approximately 27% of completer study subjects who entered the open-label treatment between weeks 
48 to 144 on Cimzia 200 mg every 2 weeks had their dose increased to Cimzia 400 mg every 2 weeks 
for maintenance of response. In an analysis in which all patients with treatment failures were 
considered non-responders, the maintenance of response of the Cimzia 200 mg every 2 weeks 
treatment group for the respective endpoint, after an additional 96 weeks of open-label therapy, was 
84.5% for PASI 75 for study subjects who were responders at Week 16  and 78.4% for PGA clear or 
almost clear. The maintenance of response of the Cimzia 400 mg every 2 weeks treatment group, who 
entered the open-label period at Cimzia 200 mg every 2 weeks, was 84.7% for PASI 75 for study 
subjects who were responders at Week 16 and 73.1% for PGA clear or almost clear.  
 



91 

These response rates were based on a logistic regression model where missing data were imputed over 
48 or 144 weeks using multiple imputation (MCMC method) combined with NRI for treatment 
failures.  
 
In the CIMPACT study, among PASI 75 responders at Week 16 who received Cimzia 400 mg every 2 
weeks and were re-randomized to either Cimzia 400 mg every 2 weeks, Cimzia 200 mg every 2 
weeks, or placebo, there was a higher percentage of PASI 75 responders at Week 48 in the Cimzia 
groups as compared to placebo (98.0%, 80.0%, and 36.0%, respectively). Among PASI75 responders 
at Week 16 who received Cimzia 200 mg every 2 weeks and were re-randomized to either Cimzia 400 
mg every 4 weeks, Cimzia 200 mg every 2 weeks, or placebo, there was also a higher percentage of 
PASI 75 responders at Week 48 in the Cimzia groups as compared to placebo (88.6%, 79.5%, and 
45.5%, respectively). Non-responder imputation was used for missing data. 
 
Quality of life / Patient reported outcomes 
 
Statistically significant improvements at Week 16 (CIMPASI-1 and CIMPASI-2) from baseline 
compared to placebo were demonstrated in the DLQI (Dermatology Life Quality Index). Mean 
decreases (improvements) in DLQI from baseline ranged from -8.9 to -11.1 with Cimzia 200 mg every 
2 weeks, from -9.6 to -10.0 with Cimzia 400 mg every 2 weeks, versus -2.9 to -3.3 for placebo at 
Week 16.  
 
In addition, at Week 16, Cimzia treatment was associated with a greater proportion of patients 
achieving a DLQI score of  0 or 1 (Cimzia 400 mg every 2 weeks, 45.5% and 50.6% respectively; 
Cimzia 200 mg every 2 weeks, 47.4% and 46.2% respectively, versus placebo, 5.9% and 8.2% 
respectively).  
 
Improvements in DLQI score were sustained or slightly decreased through Week 144. 
 
Cimzia-treated patients reported greater improvements compared to placebo in the Hospital Anxiety 
and Depression Scale (HADS)-D. 
 
Immunogenicity 
 
The data below reflect the percentage of patients whose test results were considered positive for 
antibodies to certolizumab pegol in an ELISA and later in a more sensitive method, and are highly 
dependent on the sensitivity and specificity of the assay.  The observed incidence of antibody 
(including neutralizing antibody) positivity in an assay is highly dependent on several factors, 
including assay sensitivity and specificity, assay methodology, sample handling, timing of sample 
collection, concomitant medications, and underlying disease. For these reasons, comparison of the 
incidence of antibodies to certolizumab pegol in the studies described below with the incidence of 
antibodies in other studies or to other products may be misleading. 
 
Rheumatoid arthritis 
The overall percentage of patients with antibodies to Cimzia detectable on at least 1 occasion 
was 9.6% in RA placebo-controlled trials. Approximately one-third of antibody-positive patients had 
antibodies with neutralising activity in vitro. Patients treated with concomitant immunosuppressants 
(MTX) had a lower rate of antibody development than patients not taking immunosuppressants at 
baseline. Antibody formation was associated with lowered drug plasma concentration and in some 
patients, reduced efficacy. 
 
In 2 long-term (up to 5 years of exposure) open-label studies, the overall percentage of patients with 
antibodies to Cimzia detectable on at least one occasion was 13% (8.4% of the overall patients had 
transient formation of antibodies and an additional 4.7% had persistent formation of antibodies to 
Cimzia). The overall percentage of patients that were antibody positive with a persistent reduction of 
drug plasma concentration was estimated to be 9.1%. Similar to the placebo-controlled studies, 
antibody positivity was associated with reduced efficacy in some patients. 



92 

 
A pharmacodynamic model based on the Phase III trial data predicts that around 15% of the patients 
develop antibodies in 6 months at the recommended dose regimen (200 mg every 2 weeks following a 
loading dose) without MTX co-treatment. This number decreases with increasing doses of 
concomitant MTX treatment. These data are reasonably in agreement with observed data. 
 
 
Psoriatic arthritis 
The overall percentage of patients with antibodies to Cimzia detectable on at least one occasion up to 
Week 24 was 11.7% in the Phase III placebo-controlled trial in patients with psoriatic arthritis. 
Antibody formation was associated with lowered drug plasma concentration.  
 
Over the course of the entire study (up to 4 years of exposure), the overall percentage of patients with 
antibodies to Cimzia detectable on at least one occasion was 17.3% (8.7% had transient formation and 
an additional 8.7% had persistent formation of antibodies to Cimzia). The overall percentage of 
patients that were antibody positive with a persistent reduction of drug plasma concentration was 
estimated to be 11.5%. 
 
Plaque psoriasis 
In the Phase III placebo- and active-controlled studies, the percentages of patients who were positive 
for antibodies to Cimzia on at least one occasion during treatment up to Week 48 were 8.3 % (22/265) 
and 19.2% (54/281) for the Cimzia 400 mg every 2 weeks and Cimzia 200 mg every 2 weeks 
respectively. In CIMPASI-1 and CIMPASI-2, sixty patients were antibody positive, 27 of these 
patients were evaluable for neutralizing antibodies and tested positive. First occurrences of antibody 
positivity in the open-label treatment period were observed in 2.8% (19/668) of patients. Antibody 
positivity was associated with lowered drug plasma concentration and in some patients with reduced 
efficacy. 
 
 
Axial spondyloarthritis 
AS001 
The overall percentage of patients with antibodies to Cimzia detectable on at least one occasion up to 
Week 24 was 4.4% in the AS001 phase III placebo-controlled trial in patients with axial 
spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis 
subpopulations). Antibody formation was associated with lowered drug plasma concentration. 

Over the course of the entire study (up to 192 weeks), the overall percentage of patients with 
antibodies to Cimzia detectable on at least one occasion was 9.6% (4.8% had transient formation and 
an additional 4.8% had persistent formation of antibodies to Cimzia). The overall percentage of 
patients that were antibody positive with a persistent reduction of drug plasma concentration was 
estimated to be 6.8%. 
 
AS0006 and C-OPTIMISE  
A more sensitive and drug tolerant assay was used for the first time in the AS0006 study (and later 
also in the C-OPTIMISE study), resulting in a greater proportion of samples having measurable 
antibodies to Cimzia and thus a greater incidence of patients being classed as antibody positive. In 
AS0006,  the overall incidence of patients who were antibody positive Cimzia was 97% 
(248/255 patients) after up to 52 weeks of treatment. Only the highest titers were associated with 
reduced Cimzia plasma levels, however, no impact on efficacy was observed. Similar results in 
relation to antibodies to Cimzia were seen in C-OPTIMISE. Results from C-OPTIMISE also indicated 
that a reduction of the dose to Cimzia 200 mg every 4 weeks did not change immunogenicity 
outcomes. 

 

About 22% (54/248) of the patients in AS0006 who were anti-Cimzia antibody positive at any time, 
had antibodies that were classified as neutralizing. The neutralizing status of antibodies in C-
OPTIMISE was not assessed. 



93 

 
5.2 Pharmacokinetic properties 
 
Certolizumab pegol plasma concentrations were broadly dose-proportional. Pharmacokinetics 
observed in patients with rheumatoid arthritis and psoriasis were consistent with those seen in healthy 
subjects. 
 
Absorption 
Following subcutaneous administration, peak plasma concentrations of certolizumab pegol were 
attained between 54 and 171 hours post-injection. Certolizumab pegol has a bioavailability (F) of 
approximately 80% (range 76% to 88%) following subcutaneous administration compared to 
intravenous administration. 
 
Distribution 
The apparent volume of distribution (V/F) was estimated at 8.01 l in a population pharmacokinetic 
analysis of patients with rheumatoid arthritis and at 4.71 l in a population pharmacokinetic analysis of 
patients with plaque psoriasis. 
 
Biotransformation and elimination 
PEGylation, the covalent attachment of PEG polymers to peptides, delays the elimination of these 
entities from the circulation by a variety of mechanisms, including decreased renal clearance, 
decreased proteolysis, and decreased immunogenicity. Accordingly, certolizumab pegol is an antibody 
Fab' fragment conjugated with PEG in order to extend the terminal plasma elimination half-life of the 
Fab' to a value comparable with a whole antibody product. The terminal elimination phase half-life 
(t1/2) was approximately 14 days for all doses tested.  
 
Clearance following subcutaneous dosing was estimated to be 21.0 ml/h in a rheumatoid arthritis 
population pharmacokinetic analysis, with an inter-subject variability of 30.8% (CV) and an inter-
occasion variability of 22.0%. When assessed using the previous ELISA method, the presence of 
antibodies to certolizumab pegol resulted in an approximately three-fold increase in clearance. 
Compared with a 70 kg person, clearance is 29% lower and 38% higher, respectively, in individual RA 
patients weighing 40 kg and 120 kg. The clearance following subcutaneous dosing in patients with 
psoriasis was 14 ml/h with an inter-subject variability of 22.2% (CV). 
 
The Fab' fragment comprises protein compounds and is expected to be degraded to peptides and amino 
acids by proteolysis. The de-conjugated PEG component is rapidly eliminated from plasma and is to 
an unknown extent excreted renally. 
 
Special populations 
Renal impairment 
Specific clinical trials have not been performed to assess the effect of renal impairment on the 
pharmacokinetics of certolizumab pegol or its PEG fraction. However, population pharmacokinetic 
analysis based on subjects with mild renal impairment showed no effect of creatinine clearance. There 
are insufficient data to provide a dosing recommendation in moderate and severe renal impairment. 
The pharmacokinetics of the PEG fraction of certolizumab pegol are expected to be dependent on 
renal function but have not been assessed in patients with renal impairment. 
 
Hepatic impairment 
Specific clinical trials have not been performed to assess the effect of hepatic impairment on the 
pharmacokinetics of certolizumab pegol. 
 
Elderly patients (≥ 65 years old) 
Specific clinical trials have not been performed in elderly patients subjects. However, no effect of age 
was observed in a population pharmacokinetic analysis in patients with rheumatoid arthritis in 
which 78 subjects (13.2% of the population) were aged 65 or greater and the oldest subject was 
aged 83 years. No effect of age was observed in a population pharmacokinetic analysis in adult 
patients with plaque psoriasis. 



94 

 
Gender 
There was no effect of gender on the pharmacokinetics of certolizumab pegol. As clearance decreases 
with decreasing body weight, females may generally obtain somewhat higher systemic exposure of 
certolizumab pegol. 
 
Pharmacokinetic/pharmacodynamic relationship 
On the basis of Phase II and Phase III clinical trial data in patients with rheumatoid arthritis, a 
population exposure-response relationship was established between average plasma concentration of 
certolizumab pegol during a dosing interval (Cavg) and efficacy (ACR 20 responder definition). The 
typical Cavg that produces half the maximum probability of ACR 20 response (EC50) was 17 µg/ml 
(95% CI: 10-23 µg/ml). Similarly, on the basis of Phase III clinical trial data in patients with psoriasis, 
a population exposure-response relationship was established between plasma concentration of 
certolizumab pegol and PASI with an EC90 of 11.1 µg/ml. 
 
5.3 Preclinical safety data 
 
The pivotal non-clinical safety studies were conducted in the cynomolgus monkey. In rats and 
monkeys, at doses higher than those given to humans, histopathology revealed cellular vacuolation, 
present mainly in macrophages, in a number of organs (lymph nodes, injection sites, spleen, adrenal, 
uterine, cervix, choroid plexus of the brain, and in the epithelial cells of the choroid plexus). It is likely 
that this finding was caused by cellular uptake of the PEG moiety. In vitro functional studies of human 
vacuolated macrophages indicated all functions tested were retained. Studies in rats indicated that 
> 90% of the administered PEG was eliminated in 3 months following a single dose, with the urine 
being the main route of excretion. 
 
Certolizumab pegol does not cross-react with rodent TNF. Therefore, reproductive toxicology studies 
have been performed with a homologous reagent recognising rat TNF. The value of these data to the 
evaluation of human risk may be limited. No adverse effects were seen on maternal well-being or 
female fertility, embryo-foetal and peri- and post-natal reproductive indices in rats using a rodent anti-
rat TNFα PEGylated Fab' (cTN3 PF) following sustained TNFα suppression. In male rats, reduced 
sperm motility and a trend of reduced sperm count were observed. 
 
Distribution studies have demonstrated that placental and milk transfer of cTN3 PF to the foetal and 
neonatal circulation is negligible. Certolizumab pegol does not bind to the human neonatal Fc receptor 
(FcRn). Data from a human closed-circuit placental transfer model ex vivo suggest low or negligible 
transfer to the foetal compartment. In addition, experiments of FcRn-mediated transcytosis in cells 
transfected with human FcRn showed negligible transfer (see section 4.6).  
 
No mutagenic or clastogenic effects were demonstrated in preclinical studies. Carcinogenicity studies 
have not been performed with certolizumab pegol. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium acetate 
Sodium chloride 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 



95 

6.3 Shelf life 
 
2 years. 
See also section 6.4 for shelf-life related to storage at room temperature up to a maximum of 25°C. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C). 
Do not freeze. 
Keep the dose-dispenser cartridge in the outer carton in order to protect from light. 
The dose-dispenser cartridges may be stored at room temperature (up to 25°C) for a single period of 
maximum 10 days with protection from light. At the end of this period the dose-dispenser cartridges 
must be used or discarded. 
 
6.5 Nature and contents of container 
 
One ml dose-dispenser cartridge containing a pre-filled syringe (type I glass) with a plunger stopper 
(bromobutyl rubber). The pre-filled syringe contains 200 mg of certolizumab pegol. The needle shield 
is styrene butadiene rubber which contains a derivative of natural rubber latex (see section 4.4). 
  
Pack size of 2 dose-dispenser cartridges and 2 alcohol wipes. 
Multipack containing 6 (3 packs of 2) dose-dispenser cartridge and 6 (3 packs of 2) alcohol wipes. 
Multipack containing 10 (5 packs of 2) dose-dispenser cartridge and 10 (5 packs of 2) alcohol wipes. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Comprehensive instructions for the preparation and administration of Cimzia in a dose-dispenser 
cartridge are given in the package leaflet and in the user manual provided with the electromechanical 
injection device ava. 
This medicinal product is for single use only. Any unused product or waste material should be 
disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
B-1070 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/008  
EU/1/09/544/009  
EU/1/09/544/010  
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 01 October 2009 
Date of latest renewal: 16 May 2014 
 
 



96 

10. DATE OF REVISION OF THE TEXT 
 
{MM/YYYY} 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

  



97 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURERS 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 

 



98 

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer of the biological active substance 
 
UCB Farchim SA 
Zone Industrielle de Planchy d’Avau 
Chemin de Croix Blanche 10 
CH-1630 Bulle 
Switzerland 
 
Name and address of the manufacturer responsible for batch release 
 
UCB Pharma S.A. 
Chemin du Foriest 
B-1420 Braine l'Alleud 
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. 

If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time. 
 



99 

 Additional risk minimisation measures 
 

The marketing authorisation holder (MAH) shall ensure that, prior to launch, all physicians who 
are expected to prescribe/use Cimzia are provided with a physician information pack containing 
the following: 

 The Summary of Product Characteristics 
 Patient Reminder Card 

  



100 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 

 
  



101 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
A. LABELLING 

  



102 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Outer carton (for packs of 2 pre-filled syringes and 2 alcohol wipes) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in pre-filled syringe 
certolizumab pegol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled syringe contains 200 mg certolizumab pegol in one ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium acetate, sodium chloride and water for injections. 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled syringe 
2 single-use pre-filled syringes 
2 alcohol wipes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before 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(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the pre-filled syringe in the outer carton in order to protect from light. 
 



103 

 
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 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
1070 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cimzia 200 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN:  
NN:   



104 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Multipack of 6 (3 packs of 2 pre-filled syringes and 2 alcohol wipes) 

(with Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in pre-filled syringe 
certolizumab pegol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled syringe contains 200 mg certolizumab pegol in one ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium acetate, sodium chloride and water for injections. 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled syringe 
Multipack: 6 (3 x 2) single-use pre-filled syringes and 6 (3 x 2) alcohol wipes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before 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(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the pre-filled syringe in the outer carton in order to protect from light. 
 



105 

 
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 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
1070 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cimzia 200 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN:  
NN: 
  



106 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Multipack of 10 (5 packs of 2 pre-filled syringes and 2 alcohol wipes) 
(with Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in pre-filled syringe 
certolizumab pegol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled syringe contains 200 mg certolizumab pegol in one ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium acetate, sodium chloride and water for injections. 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled syringe 
Multipack: 10 (5 x 2) single-use pre-filled syringes and 10 (5 x 2) alcohol wipes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before 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(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the pre-filled syringe in the outer carton in order to protect from light. 
 



107 

 
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 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
1070 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/004 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cimzia 200 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN:  
NN:  
  



108 

PARTICULARS TO APPEAR ON THE INTERMEDIATE PACKAGING 
 
Intermediate carton within Multipack of 6 (for 2 pre-filled syringes and 2 alcohol wipes) 
(without Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in pre-filled syringe 
certolizumab pegol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled syringe contains 200 mg certolizumab pegol in one ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium acetate, sodium chloride and water for injections. 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled syringe 
2 single-use pre-filled syringes  
2 alcohol wipes  
Component of a multipack, cannot be sold separately 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before 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(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



109 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the pre-filled 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 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
1070 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cimzia 200 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Not applicable.  



110 

PARTICULARS TO APPEAR ON THE INTERMEDIATE PACKAGING 
 
Intermediate carton within Multipack of 10 (for 2 pre-filled syringes and 2 alcohol wipes) 
(without Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in pre-filled syringe 
certolizumab pegol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled syringe contains 200 mg certolizumab pegol in one ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium acetate, sodium chloride and water for injections. 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled syringe 
2 single-use pre-filled syringes 
2 alcohol wipes  
Component of a multipack, cannot be sold separately 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before 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(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



111 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the pre-filled 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 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
1070 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/004 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cimzia 200 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Not applicable. 
  



112 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Outer carton (for packs of 2 pre-filled syringes with needle guard and 2 alcohol wipes) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in pre-filled syringe 
certolizumab pegol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled syringe contains 200 mg certolizumab pegol in one ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium acetate, sodium chloride and water for injections. 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled syringe 
2 single-use pre-filled syringes with needle guard 
2 alcohol wipes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before 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(S), IF NECESSARY 
 
For healthcare professionals only. 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



113 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the pre-filled 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 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
1070 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/003 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cimzia 200 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN:  
NN: 



114 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY BACKING TEXT  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in pre-filled syringe 
certolizumab pegol 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
UCB 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Read the package leaflet before use 
 
  



115 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Outer carton (for packs of 2 pre-filled pens and 2 alcohol wipes) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in pre-filled pen 
certolizumab pegol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled pen contains 200 mg certolizumab pegol in one ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium acetate, sodium chloride and water for injections. 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled pen (AutoClicks) 
2 single-use AutoClicks pre-filled pens 
2 alcohol wipes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before 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(S), 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. 
 
 



116 

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 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
1070 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/005 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cimzia 200 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN:  
NN: 



117 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton Multipack of 6 (3 packs of 2 pre-filled pens and 2 alcohol wipes)  
(with Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in pre-filled pen 
certolizumab pegol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled pen contains 200 mg certolizumab pegol in one ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium acetate, sodium chloride and water for injections. 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled pen (AutoClicks) 
Multipack: 6 (3 x 2) single-use AutoClicks pre-filled pens and 6 (3 x 2) alcohol wipes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before 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(S), 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. 
 



118 

 
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 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
1070 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/006 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cimzia 200 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN:  
NN: 
  



119 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton Multipack of 10 (5 packs of 2 pre-filled pens and 2 alcohol wipes) 
(with Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in pre-filled pen 
certolizumab pegol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled pen contains 200 mg certolizumab pegol in one ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium acetate, sodium chloride and water for injections. 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled pen (AutoClicks) 
Multipack: 10 (5 x 2) single-use AutoClicks pre-filled pens and 10 (5 x 2) alcohol wipes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before 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(S), 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. 
 



120 

 
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 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
1070 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/007 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cimzia 200 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN:  
NN: 
  



121 

PARTICULARS TO APPEAR ON THE INTERMEDIATE PACKAGING 
 
Intermediate carton within Multipack of 6 (for 2 pre-filled pens and 2 alcohol wipes)  
(without blue box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in pre-filled pen 
certolizumab pegol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled pen contains 200 mg certolizumab pegol in one ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium acetate, sodium chloride and water for injections. 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled pen (AutoClicks) 
2 single-use AutoClicks pre-filled pens 
2 alcohol wipes.  
Component of a multipack, cannot be sold separately 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before 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(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



122 

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 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
1070 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/006 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cimzia 200 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Not applicable.   



123 

PARTICULARS TO APPEAR ON THE INTERMEDIATE PACKAGING 
 
Intermediate carton within Multipack of 10 (for 2 pre-filled pens and 2 alcohol wipes)  
(without Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in pre-filled pen 
certolizumab pegol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled pen contains 200 mg certolizumab pegol in one ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium acetate, sodium chloride and water for injections. 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled pen (AutoClicks) 
2 AutoClicks pre-filled pens  
2 alcohol wipes 
Component of a multipack, cannot be sold separately 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before 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(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



124 

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 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
1070 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/007 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cimzia 200 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Not applicable. 
  



125 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Outer carton (for packs of 2 dose-dispenser cartridges and 2 alcohol wipes) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in dose-dispenser cartridge 
certolizumab pegol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One dose-dispenser cartridge contains 200 mg certolizumab pegol in one ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium acetate, sodium chloride and water for injections. 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in dose-dispenser cartridge 
2 single-use dose-dispenser cartridges 
2 alcohol wipes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before 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(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the dose-dispenser cartridge in the outer carton in order to protect from light. 
 



126 

 
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 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
1070 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/008 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cimzia 200 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN:  
NN:   



127 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton Multipack of 6 (3 packs of 2 dose-dispenser cartridges and 2 alcohol wipes)  
(with Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in dose-dispenser cartridge 
certolizumab pegol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One dose-dispenser cartridge contains 200 mg certolizumab pegol in one ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium acetate, sodium chloride and water for injections. 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in dose-dispenser cartridge 
Multipack: 6 (3 x 2) single-use dose-dispenser cartridges and 6 (3 x 2) alcohol wipes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before 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(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the dose-dispenser cartridge in the outer carton in order to protect from light. 
 



128 

 
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 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
1070 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/009 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cimzia 200 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN:  
NN: 
  



129 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton Multipack of 10 (5 packs of 2 dose-dispenser cartridges and 2 alcohol wipes) 

(with Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in dose-dispenser cartridge 
certolizumab pegol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One dose-dispenser cartridge contains 200 mg certolizumab pegol in one ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium acetate, sodium chloride and water for injections. 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in dose-dispenser cartridge 
Multipack: 10 (5 x 2) single-use dose-dispenser cartridge and 10 (5 x 2) alcohol wipes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before 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(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the dose-dispenser cartridge in the outer carton in order to protect from light. 
 



130 

 
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 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
1070 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/010 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cimzia 200 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN:  
NN:  
 
 
 
 
 
 
 
 



131 

PARTICULARS TO APPEAR ON THE INTERMEDIATE PACKAGING 
 
Intermediate carton within Multipack of 6 (for 2 dose-dispenser cartridges and 2 alcohol wipes) 
(without Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in dose-dispenser cartridge 
certolizumab pegol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One dose-dispenser cartridge contains 200 mg certolizumab pegol in one ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium acetate, sodium chloride and water for injections. 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in dose-dispenser cartridge 
2 single-use dose-dispenser cartridges 
2 alcohol wipes  
Component of a multipack, cannot be sold separately 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before 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(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



132 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the dose-dispenser cartridge 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 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
1070 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/009 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cimzia 200 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Not applicable.  



133 

PARTICULARS TO APPEAR ON THE INTERMEDIATE PACKAGING 
 
Intermediate carton within Multipack of 10 (for 2 dose-dispenser cartridges and 2 alcohol wipes) 
(without Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cimzia 200 mg solution for injection in dose-dispenser cartridge 
certolizumab pegol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One dose-dispenser cartridge contains 200 mg certolizumab pegol in one ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium acetate, sodium chloride and water for injections. 
See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in dose-dispenser cartridge 
2 single-use dose-dispenser cartridges 
2 alcohol wipes  
Component of a multipack, cannot be sold separately 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before 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(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



134 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the dose-dispenser cartridge 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 
 
UCB Pharma S.A. 
Allée de la Recherche 60 
1070 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/544/010 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cimzia 200 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Not applicable. 



135 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SYRINGE/PEN/DOSE-DISPENSER CARTRIDGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Cimzia 200 mg injection 
certolizumab pegol 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 ml 
 
 
6. OTHER 
 
  



136 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
  



137 

Package leaflet: Information for the user 
 

Cimzia 200 mg solution for injection in pre-filled syringe 
certolizumab pegol 

 
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. 
- If you have any further questions, please ask your doctor, pharmacist or nurse. 
- 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, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Cimzia is and what it is used for 
2. What you need to know before you use Cimzia 
3. How to use Cimzia 
4. Possible side effects 
5. How to store Cimzia 
6. Contents of the pack and other information 
 
Your physician will also give you a Patient Reminder Card, which contains important safety information 
of which you need to be aware before you are given Cimzia and during treatment with Cimzia. Keep 
this Patient Reminder Card with you. 
 
 
1. What Cimzia is and what it is used for 
 
Cimzia contains the active substance certolizumab pegol, a human antibody fragment. Antibodies are 
proteins that specifically recognise and bind to other proteins. Cimzia binds to a specific protein called 
tumour necrosis factor α (TNFα). Thereby this TNFα is blocked by Cimzia and this decreases 
inflammation diseases such as in rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis and 
psoriasis. Medicines that bind to TNFα are also called TNF blockers. 
 
Cimzia is used in adults for the following inflammatory diseases:  
 rheumatoid arthritis, 
 axial spondyloarthritis (including ankylosing spondylitis and axial spondyloarthritis without 

radiographic evidence of ankylosing spondylitis), 
 psoriatic arthritis 
 plaque psoriasis 
 
Rheumatoid arthritis 
Cimzia is used to treat rheumatoid arthritis. Rheumatoid arthritis is an inflammatory disease of the 
joints. If you have moderate to severe active rheumatoid arthritis, you may first be given other 
medicines usually methotrexate. If you do not respond well enough to these medicines, you will be 
given Cimzia in combination with methotrexate to treat your rheumatoid arthritis. If your doctor 
determines that methotrexate is inappropriate, Cimzia can be given alone. 
 
Cimzia in combination with methotrexate can also be used to treat severe, active and progressive 
rheumatoid arthritis without previous use of methotrexate or other medicines. 
 
Cimzia, which you will take in combination with methotrexate, is used to: 
 reduce the signs and symptoms of your disease, 
 slow down the damage to the cartilage and bone of the joints caused by the disease, 
 improve your physical function and performance of daily tasks. 
 



138 

Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing 
spondylitis 
Cimzia is used to treat severe active ankylosing spondylitis and axial spondyloarthritis without 
radiographic evidence of ankylosing spondylitis (sometimes referred to as non-radiographic axial 
spondyloarthritis). These diseases are inflammatory diseases of the spine. If you have ankylosing 
spondylitis or non-radiographic axial spondyloarthritis you will first be given other medicines. If you 
do not respond well enough to these medicines, you will be given Cimzia to: 
 reduce the signs and symptoms of your disease, 
 improve your physical function and performance of daily tasks. 
 
Psoriatic arthritis 
Cimzia is used to treat active psoriatic arthritis. Psoriatic arthritis is an inflammatory disease of the 
joints, usually accompanied by psoriasis. If you have active psoriatic arthritis you will first be given 
other medicines, usually methotrexate. If you do not respond well enough to these medicines, you will 
be given Cimzia in combination with methotrexate to: 
 reduce the signs and symptoms of your disease, 
 improve your physical function and performance of daily tasks. 
If your doctor determines that methotrexate is inappropriate, Cimzia can be given alone. 
 
Plaque psoriasis 
Cimzia is used to treat moderate to severe plaque psoriasis. Plaque psoriasis is an inflammatory 
disease of the skin, and can also affect your scalp and nails.  
Cimzia is used to reduce skin inflammation and other signs and symptoms of your disease.  
 
 
2. What you need to know before you use Cimzia 
 
Do NOT use Cimzia 
- If you are ALLERGIC (hypersensitive) to certolizumab pegol or any of the other ingredients of 

this medicine (listed in section 6) 
- If you have a severe infection, including active TUBERCULOSIS (TB). 
- If you have moderate to severe HEART FAILURE. Tell your doctor if you have had or have a 

serious heart condition. 
 
Warnings and precautions 
 
Tell your doctor before treatment with Cimzia if any of the following applies to you: 
 
Allergic reactions 
- If you experience ALLERGIC REACTIONS such as chest tightness, wheezing, dizziness, 

swelling or rash, stop using Cimzia and contact your doctor IMMEDIATELY. Some of these 
reactions could occur after the first administration of Cimzia. 

-  If you have ever had an allergic reaction to latex. 
 
Infections 
- If you have had RECURRENT or OPPORTUNISTIC INFECTIONS or other conditions that 

increase the risk of infections (such as treatment with immunosuppressants, which are 
medicines that could reduce your ability to fight infections). 

- If you have an infection or if you develop symptoms such as fever, wounds, tiredness or dental 
problems. You might get an infection more easily while you are being treated with Cimzia, 
including serious, or in rare cases, life-threatening infections. 

- TUBERCULOSIS (TB) cases have been reported in patients treated with Cimzia, your doctor 
will check you for signs and symptoms of tuberculosis before starting Cimzia. This will include 
a thorough medical history, a chest X-ray and a tuberculin test. The conduct of these tests 
should be recorded on your Patient Reminder Card. If latent (inactive) tuberculosis is diagnosed, 
you might be required to receive appropriate anti-tuberculosis medicines before starting Cimzia. 
In rare occasions tuberculosis can develop during therapy even if you have received preventive 



139 

treatment for tuberculosis. It is very important that you tell your doctor if you have ever had 
tuberculosis, or if you have been in close contact with someone who has had tuberculosis. If 
symptoms of tuberculosis (persistent cough, weight loss, listlessness, mild fever), or any other 
infection appear during or after therapy with Cimzia tell your doctor immediately. 

- If you are at risk of or are a carrier of or have active HEPATITIS B VIRUS (HBV) infection, 
Cimzia may increase the risk of reactivation in people who carry this virus. If this occurs, you 
should stop using Cimzia. Your doctor should test you for HBV before starting Cimzia. 

 
Heart failure 
- If you have mild HEART FAILURE and you are being treated with Cimzia, your heart failure 

status must be closely monitored by your doctor. It is important to tell your doctor if you have 
had or have a serious heart condition. If you develop new or worsening symptoms of heart 
failure (e.g. shortness of breath or swelling of your feet), you must contact your doctor 
immediately. Your doctor may decide to stop treatment with Cimzia. 

 
Cancer 
- It is uncommon, but cases of certain types of CANCER have been reported in patients treated 

with Cimzia or other TNF blockers. People with more severe rheumatoid arthritis that have had 
the disease for a long time may have a higher than average risk of getting a kind of cancer that 
affects the lymph system, called lymphoma. If you take Cimzia, your risk of getting lymphoma 
or other cancers may increase. In addition, uncommon cases of non-melanoma skin cancer have 
been observed in patients taking Cimzia. If new skin lesions appear during or after therapy with 
Cimzia or existing skin lesions change appearance, tell your doctor.  

- There have been cases of cancers, including unusual types, in children and teenage patients 
taking TNF-blocking agents, which sometimes resulted in death (see further down “Children 
and adolescents”). 

 
Other disorders 
- Patients with chronic obstructive pulmonary disease (COPD), or who are heavy smokers, may 

be at increased risk for cancer with Cimzia treatment. If you have COPD or are a heavy smoker, 
you should discuss with your doctor whether treatment with a TNF blocker is appropriate for 
you. 

- If you have a nervous system disorder, such as multiple sclerosis, your doctor will decide 
whether you should use Cimzia. 

- In some patients the body may fail to produce enough of the blood cells that help your body 
fight infections or help you to stop bleeding. If you develop a fever that does not go away, 
bruise or bleed very easily or look very pale, call your doctor immediately. Your doctor may 
decide to stop treatment with Cimzia. 

- It is uncommon, but symptoms of a disease called lupus (for example persistent rash, fever, joint 
pain and tiredness) may occur. If you experience these symptoms, contact your doctor. Your 
doctor may decide to stop treatment with Cimzia. 

 
Vaccinations 
- Talk to your doctor if you have had, or are due to have a vaccine. You should not receive certain 

(live) vaccines while using Cimzia. 
- Certain vaccinations may cause infections. If you received Cimzia while you were pregnant, 

your baby may be at higher risk for getting such an infection for up to approximately five 
months after the last dose you received during pregnancy. It is important that you tell your 
baby's doctors and other health care professionals about your Cimza use so they can decide 
when your baby should receive any vaccine. 

 
Operations or dental procedures 
- Talk to your doctor if you are going to have any operations or dental procedures. Tell your 

surgeon or dentist performing the procedure that you are having treatment with Cimzia by 
showing them your Patient Reminder Card. 

 



140 

Children and adolescents 
Cimzia is not recommended for use in children and adolescents under the age of 18 years. 
 
Other medicines and Cimzia 
You should NOT take Cimzia if you are using the following medicines used to treat rheumatoid 
arthritis: 
- anakinra  
- abatacept 
If you have questions, please ask your doctor. 
 
Cimzia can be taken together with: 
- methotrexate,  
- corticosteroids, or  
- pain medicines including nonsteroidal anti-inflammatory medicines (also called NSAIDs). 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
There is limited experience with Cimzia in pregnant women. 
Cimzia should be used during pregnancy only if clearly needed. If you are a woman of childbearing 
potential, discuss with your doctor regarding use of adequate contraception while using Cimzia. For 
women planning pregnancy, contraception may be considered for 5 months after the last Cimzia dose. 
 
If you received Cimzia 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 Cimzia use before the baby receives any vaccine (for more information see section on 
vaccinations). 
 
Cimzia can be used during breastfeeding. 
 
Driving and using machines 
Cimzia may have a minor influence on your ability to drive and use machines. Dizziness (including 
room spinning sensation, blurred vision and tiredness) may occur after you take Cimzia. 
 
Cimzia contains sodium acetate and sodium chloride 
This medicinal product contains less than 1 mmol sodium (23 mg) per 400 mg, i.e. essentially 
‘sodium-free’. 
 
 
3. How to use Cimzia 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Rheumatoid arthritis 
 The starting dose for adults with rheumatoid arthritis is 400 mg given at weeks 0, 2 and 4.  
 This is followed by a maintenance dose of 200 mg every 2 weeks. If you respond to the 

medicine, your doctor may prescribe an alternative maintenance dosing of 400 mg 
every 4 weeks.  

 Methotrexate is continued while using Cimzia. If your doctor determines that methotrexate is 
inappropriate, Cimzia can be given alone. 

 



141 

Axial spondyloarthritis 
 The starting dose for adults with axial spondyloarthritis is 400 mg given at weeks 0, 2 and 4.  
 This is followed by a maintenance dose of 200 mg every 2 weeks (from week 6) or 400 mg 

every 4 weeks (from week 8) as instructed by your physician. If you have received Cimzia for at 
least 1 year and respond to the medicine, your physician may prescribe a reduced maintenance 
dose of 200 mg every 4 weeks. 

 
Psoriatic arthritis 
 The starting dose for adults with psoriatic arthritis is 400 mg given at weeks 0, 2 and 4.  
 This is followed by a maintenance dose of 200 mg every 2 weeks. If you respond to the 

medicine, your doctor may prescribe an alternative maintenance dosing of 400 mg 
every 4 weeks.  

 Methotrexate is continued while using Cimzia. If your doctor determines that methotrexate is 
inappropriate, Cimzia can be given alone. 

 
Plaque psoriasis 
 The starting dose for adults with plaque psoriasis is 400 mg every 2 weeks given at 

weeks 0, 2 and 4.  
 This is followed by a maintenance dose of 200 mg every 2 weeks, or 400 mg every 2 weeks as 

instructed by your physician.  
 
How Cimzia is given 
Cimzia will usually be given to you by a specialist doctor or healthcare professional. You will be 
given Cimzia as either one (200 mg dose) or two injections (400 mg dose) under the skin 
(subcutaneous use, abbreviation: SC). It is usually injected into the thigh or tummy. However, do not 
inject in an area where the skin is reddened, bruised, or hard. 
 
Instructions for self-injecting Cimzia 
After suitable training, your doctor may also allow you to inject Cimzia yourself. Please read the 
instructions at the end of this leaflet on how to inject Cimzia. 
 
If your doctor has allowed you to self-inject, you should follow up with your doctor before you 
continue to self-inject: 
 after 12 weeks if you have rheumatoid arthritis, axial spondyloarthritis or psoriatic arthritis, or  
 after 16 weeks if you have plaque psoriasis. 
This is so that the doctor can determine if Cimzia is working for you or if another treatment needs to 
be considered. 
 
If you use more Cimzia than you should 
If your doctor has allowed you to self-inject and you accidentally inject Cimzia more frequently than 
prescribed, you should tell your doctor. Always take the Patient Reminder Card and the outer carton 
from the Cimzia package with you, even if it is empty. 
 
If you forget to use Cimzia 
If your doctor has allowed you to self-inject and you forget to give yourself an injection, you should 
inject the next dose of Cimzia as soon as you remember. Then, talk to your doctor and inject the 
following doses as instructed. 
 
If you stop using Cimzia 
Do not stop using Cimzia without talking to your doctor first. 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 



142 

Tell your doctor IMMEDIATELY if you notice any of the following side effects: 
 severe rash, hives or other signs of allergic reaction (urticaria) 
 swollen face, hands, feet (angioedema) 
 trouble breathing, swallowing (multiple causes for these symptoms) 
 shortness of breath with exertion or upon lying down or swelling of the feet (heart failure) 
 symptoms of blood disorders such as persistent fever, bruising, bleeding, paleness 

(pancytopaenia, anaemia, low platelet count, low white blood cell count) 
 serious skin rashes. These can appear as reddish target-like macules or circular patches often 

with central blisters on the trunk, skin peeling, ulcers of mouth, throat, nose, genitals and eyes 
and can be preceded by fever and flu-like symptoms. (Stevens-Johnson syndrome) 

 
Tell your doctor AS SOON AS POSSIBLE if you notice any of the following side effects: 
 signs of infection such as fever, malaise, wounds, dental problems, burning on urination  
 feeling weak or tired 
 coughing 
 tingling 
 numbness 
 double vision 
 arm or leg weakness 
 bump or open sore that doesn't heal 
 
The symptoms described above can be due to some of the side effects listed below, which have been 
observed with Cimzia: 
 
Common (may affect up to 1 in 10 people): 
 bacterial infections in any site (a collection of pus) 
 viral infections (including cold sores, shingles, and influenza) 
 fever 
 high blood pressure 
 rash or itching  
 headaches (including migraines) 
 sensory abnormalities such as numbness, tingling, burning sensation 
 feeling weak and generally unwell  
 pain 
 blood disorders 
 liver problems 
 injection site reactions 
 nausea 
 
Uncommon (may affect up to 1 in 100 people): 
 allergic conditions including allergic rhinitis and allergic reactions to the medicine (including 

anaphylactic shock) 
 antibody directed against normal tissue 
 blood and lymphatic system cancers like lymphoma and leukaemia 
 solid organ cancers 
 skin cancers, pre-cancerous skin lesions 
 benign (non-cancerous) tumours and cysts (including those of the skin) 
 heart problems including weakened heart muscle, heart failure, heart attack, chest discomfort or 

chest pressure, abnormal heart rhythm including irregular heart beats 
 oedema (swelling in the face or legs) 
 lupus (immune/connective tissue disease) symptoms (joint pain, skin rashes, photosensitivity 

and fever)  
 inflammation of the blood vessels 
 sepsis (serious infection which can result in organ failure, shock or death) 
 tuberculosis infection 



143 

 fungal infections (occur when the ability to fight off infection is lessened) 
 respiratory disorders and inflammation (including asthma, shortness of breath, cough, blocked 

sinuses, pleurisy, or difficulty breathing) 
 stomach problems including abdominal fluid collection, ulcers (including oral ulcers), 

perforation, distension, inflammation heartburn, upset, dry mouth 
 bile problems 
 muscle problems including increased muscle enzymes 
 changes in blood levels of different salts 
 changes in cholesterol and fat levels in the blood 
 blood clots in the veins or lungs 
 bleeding or bruising 
 changed numbers of blood cells, including low red cell count (anaemia), low platelet counts, 

increased platelet counts 
 swollen lymph nodes 
 flu-like symptoms, chills, altered temperature perception, night sweats, flushing 
 anxiety and mood disorders such as depression, appetite disorders, weight change 
 ringing in the ears  
 vertigo (dizziness) 
 feeling faint, including loss of consciousness 
 nerve disorders in the extremities including symptoms of numbness, tingling, burning sensation, 

dizziness, tremor 
 skin disorders such as new onset or worsening of psoriasis, inflammation of the skin (such as 

eczema), sweat gland disorders, ulcers, photosensitivity, acne, hair loss, discoloration, nail 
separation, dry skin and injuries 

 impaired healing 
 kidney and urinary problems including impairment of kidney function, blood in the urine and 

urinary disturbances  
 menstrual cycle (monthly period) disorders including lack of bleeding, or heavy or irregular 

bleeding 
 breast disorders  
 eye and eyelid inflammation, vision disturbances, problems with tears  
 some blood parameters increased (blood alkaline phosphatase increased) 
 prolonged coagulation (clotting) test times 
 
Rare (may affect up to 1 in 1,000 people): 
 gastrointestinal cancer, melanoma 
 lung inflammation (interstitial lung disease, pneumonitis) 
 stroke, blockage in blood vessels (arteriosclerosis), poor blood circulation which makes the toes 

and fingers numb and pale (Raynaud’s phenomenon), mottled purplish skin discoloration, small 
veins near the surface of the skin may become visible 

 pericardial inflammation 
 cardiac arrhythmia 
 enlarged spleen 
 increase of red cell mass 
 white blood cell morphology abnormal 
 formation of stones in the gall bladder 
 kidney problems (including nephritis) 
 immune disorders such as sarcoidosis (rash, joint pain, fever), serum sickness, inflammation of 

the fat tissue, angioneurotic oedema (swelling of the lips, face, throat) 
 thyroid disorders (goitre, tiredness, weight loss) 
 increased iron levels in the body 
 increased blood levels of uric acid  
 suicide attempt, mental impairment, delirium 
 inflammation of the nerves for hearing, seeing, or of the face, impaired coordination or balance 



144 

 increased gastrointestinal motility 
 fistula (tract from one organ to another) (any site) 
 oral disorders including pain on swallowing 
 skin sloughing, blistering, hair texture disorder 
 sexual dysfunction 
 seizure 
 worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle 

weakness) 
 Stevens-Johnson syndrome (a serious skin condition which early symptoms include malaise, 

fever, headache and rash) 
 inflammatory skin rash (erythema multiforme) 
 lichenoid reactions (itchy reddish-purple skin rash and/or threadlike white-grey lines on mucous 

membranes) 
 
Not known (frequency cannot be estimated from the available data): 
 multiple sclerosis* 
 Guillain-Barré syndrome* 
 Merkel cell carcinoma (a type of skin cancer)* 
 Kaposi’s sarcoma (a rare cancer related to infection with human herpes virus 8. Kaposi’s 

sarcoma most commonly appears as purple lesions on the skin) 
 
*These events have been related to this class of medicines but the incidence with Cimzia is not known. 
 
Other side effects 
When Cimzia has been used to treat other diseases the following uncommon side effects have 
occurred: 
 gastrointestinal stenosis (narrowing of part of the digestive system). 
 gastrointestinal obstructions (blockages of the digestive system). 
 general physical health deterioration. 
 spontaneous abortion. 
 azoospermia (lack of sperm production). 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. 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 Cimzia 
 
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 pack and syringe after EXP. The 
expiry date refers to the last day of that month. 
 
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. 
The pre-filled syringes may be stored at room temperature (up to 25°C) for a single period of 
maximum 10 days with protection from light. At the end of this period the pre-filled syringes must be 
used or discarded. 
 
Do not use this medicine if the solution is discoloured, cloudy or if you can see particles in it.  
 



145 

Do not throw away any medicines via wastewater or household waste. Ask your 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 Cimzia contains  
 The active substance is certolizumab pegol. Each pre-filled syringe contains 200 mg of 

certolizumab pegol in one ml. 
 The other ingredients are: sodium acetate, sodium chloride and water for injection (see “Cimzia 

contains sodium acetate and sodium chloride” in section 2). 
 
What Cimzia looks like and contents of the pack 
Cimzia is provided as a solution for injection in a ready to use pre-filled syringe. The solution is clear 
to opalescent, colourless to yellow. 
 
One Cimzia pack contains: 
 two pre-filled syringes of solution, and 
 two alcohol wipes (for cleansing the areas chosen for injection). 
 
Packs of 2 pre-filled syringes and 2 alcohol wipes, a multipack containing 6 (3 packs of 2) pre-filled 
syringes and 6 (3 packs of 2) alcohol wipes, and a multipack containing 10 (5 packs of 2) pre-filled 
syringes and 10 (5 packs of 2) alcohol wipes are available. 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder  
UCB Pharma S.A.        
Allée de la Recherche 60       
B-1070 Bruxelles        
Belgium         
 
Manufacturer 
UCB Pharma S.A. 
Chemin du Foriest 
B-1420 Braine l'Alleud 
Belgium 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

België/Belgique/Belgien 
UCB Pharma S.A./NV 
Tel/Tél: + 32 / (0)2 559 92 00 
 

Lietuva 
UCB Pharma Oy Finland 
Tel: + 358 9 25144221 

България 
Ю СИ БИ България ЕООД 
Teл.: + 359 (0) 2 962 30 49 

Luxembourg/Luxemburg 
UCB Pharma S.A./NV 
Tél/Tel: + 32 / (0)2 559 92 00 
 

Česká republika 
UCB s.r.o. 
Tel: + 420 221 773 411 

Magyarország 
UCB Magyarország Kft. 
Tel.: + 36-(1) 391 0060 
 

Danmark 
UCB Nordic A/S 
Tlf: + 45 / 32 46 24 00 

Malta 
Pharmasud Ltd. 
Tel: + 356 / 21 37 64 36 
 



146 

Deutschland 
UCB Pharma GmbH 
Tel: + 49 /(0) 2173 48 4848 

Nederland 
UCB Pharma B.V. 
Tel.: + 31 / (0)76-573 11 40 
 

Eesti 
UCB Pharma Oy Finland 
Tel: + 358 9 25144221 

Norge 
UCB Nordic A/S 
Tlf: + 45 / 32 46 24 00 
 

Ελλάδα 
UCB Α.Ε.  
Τηλ: + 30 / 2109974000 

Österreich 
UCB Pharma GmbH 
Tel: + 43 (0) 1 291 80 00 
 

España 
UCB Pharma S.A. 
Tel: + 34 / 91 570 34 44 

Polska 
UCB Pharma Sp. z o.o. 
Tel.: + 48 22 696 99 20 
 

France 
UCB Pharma S.A. 
Tél: + 33 / (0)1 47 29 44 35 

Portugal 
UCB Pharma (Produtos Farmacêuticos), Lda 
Tel: + 351 / 21 302 5300 
 

Hrvatska 
Medis Adria d.o.o. 
Tel: +385 (0) 1 230 34 46 
 

România 
UCB Pharma Romania S.R.L. 
Tel: + 40 21 300 29 04 
 

Ireland 
UCB (Pharma) Ireland Ltd. 
Tel: + 353 / (0)1-46 37 395 

Slovenija 
Medis, d.o.o. 
Tel: + 386 1 589 69 00 
 

Ísland 
Vistor hf. 
Tel: + 354 535 7000 

Slovenská republika 
UCB s.r.o., organizačná zložka 
Tel: + 421 (0) 2 5920 2020 
 

Italia 
UCB Pharma S.p.A. 
Tel: + 39 / 02 300 791 

Suomi/Finland 
UCB Pharma Oy Finland 
Puh/Tel: + 358 9 25144221 
 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Τηλ: + 357 22 34 74 40 
 

Sverige 
UCB Nordic A/S 
Tel: + 46 / (0) 40 29 49 00 
 

Latvija 
UCB Pharma Oy Finland 
Tel: + 358 9 25144221 
 

United Kingdom 
UCB Pharma Ltd. 
Tel : + 44 / (0)1753 534 655 
 

 
This leaflet was last revised in {MM/YYYY}  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu  
 
--------------------------------------------------------------------------------------------------------------------------- 
 



147 

INSTRUCTIONS FOR USE FOR CIMZIA INJECTION BY MEANS OF A PRE-FILLED 
SYRINGE 
After proper training, the injection can be self-administered or given by another person, for example a 
family member or friend. The following instructions explain how to inject Cimzia. Please read the 
instructions carefully and follow them step by step. You will be instructed by your doctor or healthcare 
giver on the technique of self-injection. Do not attempt to self-inject until you are sure that you 
understand how to prepare and give the injection.  
 
This injection should not be mixed in the same syringe with any other medicine. 
 
1. Setting up 
• Remove the Cimzia pack from the refrigerator. 

 If the seal(s) is missing or broken – do not use and contact your pharmacist.  
• Remove the following items from the Cimzia pack and set them up on a clean flat surface: 

– One or two pre-filled syringe(s), depending on your prescribed dose 
– One or two alcohol wipe(s) 

• Look at the expiry date on the syringe and pack. Do not use Cimzia after the expiry date which 
is stated on the pack and syringe after EXP. The expiry date refers to the last day of the month 
shown. 

• Allow the pre-filled syringe to reach room temperature. This will take 30 minutes. This will 
help reduce discomfort when injecting. 
 Do not heat the pre-filled syringe – let it warm on its own. 

• Do not remove the cap until you are ready to inject. 
• Wash your hands thoroughly. 
 
2. Choosing and preparing an injection site 
• Choose a site on your thigh or tummy. 

 

• Each new injection should be given on a separate site from the last injection site. 
 Do not inject in an area where the skin is reddened, bruised, or hard.  
 Wipe the injection site with the enclosed alcohol wipe, using a circular motion moving 

from the inside out. 
 Do not touch the area again before injecting. 
 

3. Injection 
• Do not shake the syringe. 

Check the medicine in the body of the syringe.  
 Do not use if the solution is discoloured, cloudy or if you can see particles in it.  
 You may see air bubbles - this is normal. Injecting a solution subcutaneously which 

contains air bubbles is harmless. 



148 

• Remove the cap from the needle in a straight direction, being careful not to touch the needle or 
let the needle touch any surface. Do not bend the needle. 

• Inject within 5 minutes of removing the needle cap. 
• Gently grasp the cleaned area of skin with one hand and hold firmly. 
 

 
• With the other hand, hold the syringe at a 45-degree angle to the skin. 
• With one quick, short motion, push the needle all the way into the skin. 
• Push the plunger to inject solution. It can take up to 10 seconds to empty the syringe. 
• When the syringe is empty, carefully remove the needle from the skin at the same angle at 

which it was inserted. 
• Release the skin with the first hand. 
• Use a piece of gauze, apply pressure over the injection site for a few seconds: 

 Do not rub the injection site.  
 You may cover the injection site with a small adhesive bandage, if necessary. 

 
4. After Use 
• Do not re-use the syringe or re-cap the needle. 
• After injection, immediately throw away the used syringe(s) in a special container as instructed 

by your doctor, nurse or pharmacist.  

 
• Keep the container out of the sight and reach of children. 
 If you need to have a second injection as prescribed by your doctor repeat the injection process 

starting at Step 2. 



149 

Package leaflet: Information for the user 
 

Cimzia 200 mg solution for injection in pre-filled syringe 
Pre-filled syringe with needle guard 

certolizumab pegol 
 
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. 
- If you have any further questions, please ask your doctor, pharmacist or nurse. 
- 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, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Cimzia is and what it is used for 
2. What you need to know before you use Cimzia 
3. How Cimzia will be given 
4. Possible side effects 
5.  How to store Cimzia 
6. Contents of the pack and other information 
 
Your physician will also give you a Patient Reminder Card, which contains important safety information 
of which you need to be aware before you are given Cimzia and during treatment with Cimzia. Keep 
this Patient Reminder Card with you. 
 
 
1. What Cimzia is and what it is used for 
 
Cimzia contains the active substance certolizumab pegol, a human antibody fragment. Antibodies are 
proteins that specifically recognise and bind to other proteins. Cimzia binds to a specific protein called 
tumour necrosis factor α (TNFα). Thereby this TNFα is blocked by Cimzia and this decreases 
inflammation diseases such as in rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis and 
psoriasis. Medicines that bind to TNFα are also called TNF blockers. 
 
Cimzia is used in adults for the following inflammatory diseases:  
 rheumatoid arthritis, 
 axial spondyloarthritis (including ankylosing spondylitis and axial spondyloarthritis without 

radiographic evidence of ankylosing spondylitis )  
 psoriatic arthritis.  
 plaque psoriasis 

 
Rheumatoid arthritis  
Cimzia is used to treat rheumatoid arthritis. Rheumatoid arthritis is an inflammatory disease of the 
joints. If you have moderate to severe active rheumatoid arthritis, you may first be given other 
medicines usually methotrexate. If you do not respond well enough to these medicines, you will be 
given Cimzia in combination with methotrexate to treat your rheumatoid arthritis. If your doctor 
determines that methotrexate is inappropriate, Cimzia can be given alone. 
Cimzia in combination with methotrexate can also be used to treat severe, active and progressive 
rheumatoid arthritis without previous use of methotrexate or other medicines. 
 
Cimzia, which you will take in combination with methotrexate, is used to: 
 reduce the signs and symptoms of your disease, 
 slow down the damage to the cartilage and bone of the joints caused by the disease, 
 improve your physical function and performance of daily tasks. 
  



150 

Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing 
spondylitis 
Cimzia is used to treat severe active ankylosing spondylitis and axial spondyloarthritis without 
radiographic evidence of ankylosing spondylitis (sometimes referred to as non-radiographic axial 
spondyloarthritis). These diseases are inflammatory diseases of the spine. If you have ankylosing 
spondylitis or non-radiographic axial spondyloarthritis you will first be given other medicines. If you 
do not respond well enough to these medicines, you will be given Cimzia to: 
 reduce the signs and symptoms of your disease, 
 improve your physical function and performance of daily tasks. 
 
Psoriatic arthritis 
Cimzia is used to treat active psoriatic arthritis. Psoriatic arthritis is an inflammatory disease of the 
joints, usually accompanied by psoriasis. If you have active psoriatic arthritis you will first be given 
other medicines, usually methotrexate. If you do not respond well enough to these medicines, you will 
be given Cimzia in combination with methotrexate to: 
 reduce the signs and symptoms of your disease, 
 improve your physical function and performance of daily tasks. 
If your doctor determines that methotrexate is inappropriate, Cimzia can be given alone. 
 
Plaque psoriasis 
Cimzia is used to treat moderate to severe plaque psoriasis. Plaque psoriasis is an inflammatory 
disease of the skin, and can also affect your scalp and nails.  
Cimzia is used to reduce skin inflammation and other signs and symptoms of your disease. 
 
 
2. What you need to know before you use Cimzia 
 
Do NOT use Cimzia 
- If you are ALLERGIC (hypersensitive) to certolizumab pegol or any of the other ingredients of 

this medicine (listed in section 6) 
- If you have a severe infection, including active TUBERCULOSIS (TB). 
- If you have moderate to severe HEART FAILURE. Tell your doctor if you have had or have a 

serious heart condition. 
 
Warnings and precautions 
 
Tell your doctor before treatment with Cimzia if any of the following applies to you: 
 
Allergic reactions 
- If you experience ALLERGIC REACTIONS such as chest tightness, wheezing, dizziness, 

swelling or rash, stop using Cimzia and contact your doctor IMMEDIATELY. Some of these 
reactions could occur after the first administration of Cimzia. 

-  If you have ever had an allergic reaction to latex. 
 
Infections 
- If you have had RECURRENT or OPPORTUNISTIC INFECTIONS or other conditions that 

increase the risk of infections (such as treatment with immunosuppressants, which are 
medicines that could reduce your ability to fight infections). 

- If you have an infection or if you develop symptoms such as fever, wounds, tiredness or dental 
problems. You might get an infection more easily while you are being treated with Cimzia, 
including serious, or in rare cases, life-threatening infections. 

- TUBERCULOSIS (TB) cases have been reported in patients treated with Cimzia, your doctor 
will check you for signs and symptoms of tuberculosis before starting Cimzia. This will include 
a thorough medical history, a chest X-ray and a tuberculin test. The conduct of these tests 
should be recorded on your Patient Reminder Card. If latent (inactive) tuberculosis is diagnosed, 
you might be required to receive appropriate anti-tuberculosis medicines before starting Cimzia. 
In rare occasions tuberculosis can develop during therapy even if you have received preventive 



151 

treatment for tuberculosis. It is very important that you tell your doctor if you have ever had 
tuberculosis, or if you have been in close contact with someone who has had tuberculosis. If 
symptoms of tuberculosis (persistent cough, weight loss, listlessness, mild fever), or any other 
infection appear during or after therapy with Cimzia tell your doctor immediately. 

- If you are at risk of or are a carrier of or have active HEPATITIS B VIRUS (HBV) infection, 
Cimzia may increase the risk of reactivation in people who carry this virus. If this occurs, you 
should stop using Cimzia. Your doctor should test you for HBV before starting Cimzia. 

 
Heart failure 
- If you have mild HEART FAILURE and you are being treated with Cimzia, your heart failure 

status must be closely monitored by your doctor. It is important to tell your doctor if you have 
had or have a serious heart condition. If you develop new or worsening symptoms of heart 
failure (e.g. shortness of breath or swelling of your feet), you must contact your doctor 
immediately. Your doctor may decide to stop treatment with Cimzia. 

 
Cancer 
- It is uncommon, but cases of certain types of CANCER have been reported in patients treated 

with Cimzia or other TNF blockers. People with more severe rheumatoid arthritis that have had 
the disease for a long time may have a higher than average risk of getting a kind of cancer that 
affects the lymph system, called lymphoma. If you take Cimzia, your risk of getting lymphoma 
or other cancers may increase. In addition, uncommon cases of non-melanoma skin cancer have 
been observed in patients taking Cimzia. If new skin lesions appear during or after therapy with 
Cimzia or existing skin lesions change appearance, tell your doctor. 

- There have been cases of cancers, including unusual types, in children and teenage patients 
taking TNF-blocking agents, which sometimes resulted in death (see further down “Children 
and adolescents”). 

 
Other disorders 
- Patients with chronic obstructive pulmonary disease (COPD), or who are heavy smokers, may 

be at increased risk for cancer with Cimzia treatment. If you have COPD or are a heavy smoker, 
you should discuss with your doctor whether treatment with a TNF blocker is appropriate for 
you. 

- If you have a nervous system disorder, such as multiple sclerosis, your doctor will decide 
whether you should use Cimzia. 

- In some patients the body may fail to produce enough of the blood cells that help your body 
fight infections or help you to stop bleeding. If you develop a fever that does not go away, 
bruise or bleed very easily or look very pale, call your doctor immediately. Your doctor may 
decide to stop treatment with Cimzia. 

- It is uncommon, but symptoms of a disease called lupus (for example persistent rash, fever, joint 
pain and tiredness) may occur. If you experience these symptoms, contact your doctor. Your 
doctor may decide to stop treatment with Cimzia. 

 
Vaccinations 
- Talk to your doctor if you have had, or are due to have a vaccine. You should not receive certain 

(live) vaccines while using Cimzia. 
- Certain vaccinations may cause infections. If you received Cimzia while you were pregnant, 

your baby may be at higher risk for getting such an infection for up to approximately five 
months after the last dose you received during pregnancy. It is important that you tell your 
baby's doctors and other health care professionals about your Cimza use so they can decide 
when your baby should receive any vaccine. 

 
Operations or dental procedures 
- Talk to your doctor if you are going to have any operations or dental procedures. Tell your 

surgeon or dentist performing the procedure that you are having treatment with Cimzia by 
showing them your Patient Reminder Card. 

 



152 

Children and adolescents 
Cimzia is not recommended for use in children and adolescents under the age of 18 years. 
 
Other medicines and Cimzia 
You should NOT take Cimzia if you are using the following medicines used to treat rheumatoid 
arthritis: 
- anakinra  
- abatacept 
If you have questions, please ask your doctor. 
 
Cimzia can be taken together with: 
- methotrexate,  
- corticosteroids, or  
- pain medicines including nonsteroidal anti-inflammatory medicines (also called NSAIDs). 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
There is limited experience with Cimzia in pregnant women.  
Cimzia should be used during pregnancy only if clearly needed. If you are a woman of childbearing 
potential discuss with your doctor regarding use of adequate contraception while using Cimzia. For 
women planning pregnancy, contraception may be considered for 5 months after the last Cimzia dose. 
 
If you received Cimzia 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 Cimzia use before the baby receives any vaccine (for more information see section on 
vaccinations). 
 
Cimzia can be used during breastfeeding.  
 
Driving and using machines 
Cimzia may have a minor influence on your ability to drive and use machines. Dizziness (including 
room spinning sensation, blurred vision and tiredness) may occur after you take Cimzia. 
 
Cimzia contains sodium acetate and sodium chloride 
This medicinal product contains less than 1 mmol sodium (23 mg) per 400 mg, i.e. essentially 
‘sodium-free’. 
 
 
3. How Cimzia will be given 
 
Cimzia will be given to you by your doctor or nurse, in hospital or clinic. 
 
Rheumatoid arthritis 
 The starting dose for adults with rheumatoid arthritis is 400 mg given at weeks 0, 2 and 4.  
 This is followed by a maintenance dose of 200 mg every 2 weeks. If you respond to the 

medicine, your doctor may prescribe an alternative maintenance dosing of 400 mg 
every 4 weeks.  

 Methotrexate is continued while using Cimzia. If your doctor determines that methotrexate is 
inappropriate, Cimzia can be given alone. 

 



153 

Axial spondyloarthritis 
 The starting dose for adults with axial spondyloarthritis is 400 mg given at weeks 0, 2 and 4.  
 This is followed by a maintenance dose of 200 mg every 2 weeks (from week 6) or 400 mg 

every 4 weeks (from week 8) as instructed by your physician. If you have received Cimzia for at 
least 1 year and respond to the medicine, your physician may prescribe a reduced maintenance 
dose of 200 mg every 4 weeks. 

 
Psoriatic arthritis 
 The starting dose for adults with psoriatic arthritis is 400 mg given at weeks 0, 2 and 4.  
 This is followed by a maintenance dose of 200 mg every 2 weeks. If you respond to the 

medicine, your doctor may prescribe an alternative maintenance dosing of 400 mg 
every 4 weeks.  

 Methotrexate is continued while using Cimzia. If your doctor determines that methotrexate is 
inappropriate, Cimzia can be given alone. 

 
Plaque psoriasis 
 The starting dose for adults with plaque psoriasis is 400 mg every 2 weeks given at 

weeks 0, 2 and 4.  
 This is followed by a maintenance dose of 200 mg every 2 weeks, or 400 mg every 2 weeks as 

instructed by your physician.  
 
How Cimzia is given 
Cimzia will be given to you by a specialist doctor or healthcare professional. You will be given 
Cimzia as either one (200 mg dose) or two injections (400 mg dose) under the skin (subcutaneous use, 
abbreviation: SC). It is usually injected into the thigh or tummy. However, do not inject in an area 
where the skin is reddened, bruised, or hard. 
 
If you are given too much Cimzia  
As this medecine is being given by your doctor or nurse, it is unlikely that you will be given too much. 
Always take the Patient Reminder Card with you.  
 
If you forget to use Cimzia 
If you forget or miss an appointment to receive Cimzia, make another appointment as soon as possible.  
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Tell your doctor IMMEDIATELY if you notice any of the following side effects: 
 severe rash, hives or other signs of allergic reaction (urticaria) 
 swollen face, hands, feet (angioedema) 
 trouble breathing, swallowing (multiple causes for these symptoms) 
 shortness of breath with exertion or upon lying down or swelling of the feet (heart failure) 
 symptoms of blood disorders such as persistent fever, bruising, bleeding, paleness 

(pancytopaenia, anaemia, low platelet count, low white blood cell count) 
 serious skin rashes. These can appear as reddish target-like macules or circular patches often 

with central blisters on the trunk, skin peeling, ulcers of mouth, throat, nose, genitals and eyes 
and can be preceded by fever and flu-like symptoms. (Stevens-Johnson syndrome) 

 
Tell your doctor AS SOON AS POSSIBLE if you notice any of the following side effects: 
 signs of infection such as fever, malaise, wounds, dental problems, burning on urination  
 feeling weak or tired 
 coughing. 



154 

 tingling 
 numbness 
 double vision 
 arm or leg weakness 
 bump or open sore that doesn't heal 
 
The symptoms described above can be due to some of the side effects listed below, which have been 
observed with Cimzia: 
 
Common (may affect up to 1 in 10 people): 
 bacterial infections in any site (a collection of pus) 
 viral infections (including cold sores, shingles, and influenza) 
 fever 
 high blood pressure 
 rash or itching  
 headaches (including migraines) 
 sensory abnormalities such as numbness, tingling, burning sensation 
 feeling weak and generally unwell  
 pain 
 blood disorders 
 liver problems 
 injection site reactions 
 nausea 
 
Uncommon (may affect up to 1 in 100 people): 
 allergic conditions including allergic rhinitis and allergic reactions to the medicine (including 

anaphylactic shock) 
 antibody directed against normal tissue 
 blood and lymphatic system cancers like lymphoma and leukaemia 
 solid organ cancers 
 skin cancers, pre-cancerous skin lesions 
 benign (non-cancerous) tumours and cysts (including those of the skin) 
 heart problems including weakened heart muscle, heart failure, heart attack, chest discomfort or 

chest pressure, abnormal heart rhythm including irregular heart beats 
 oedema (swelling in the face or legs) 
 lupus (immune/connective tissue disease) symptoms (joint pain, skin rashes, photosensitivity 

and fever)  
 inflammation of the blood vessels 
 sepsis (serious infection which can result in organ failure, shock or death) 
 tuberculosis infection 
 fungal infections (occur when the ability to fight off infection is lessened) 
 respiratory disorders and inflammation (including asthma, shortness of breath, cough, blocked 

sinuses, pleurisy, or difficulty breathing) 
 stomach problems including abdominal fluid collection, ulcers (including oral ulcers), 

perforation, distension, inflammation heartburn, upset, dry mouth 
 bile problems 
 muscle problems including increased muscle enzymes 
 changes in blood levels of different salts 
 changes in cholesterol and fat levels in the blood 
 blood clots in the veins or lungs 
 bleeding or bruising 
 changed numbers of blood cells, including low red cell count (anaemia), low platelet counts, 

increased platelet counts 
 swollen lymph nodes 



155 

 flu-like symptoms, chills, altered temperature perception, night sweats, flushing 
 anxiety and mood disorders such as depression, appetite disorders, weight change 
 ringing in the ears 
 vertigo (dizziness) 
 feeling faint, including loss of consciousness 
 nerve disorders in the extremities including symptoms of numbness, tingling, burning sensation, 

dizziness, tremor 
 skin disorders such as new onset or worsening of psoriasis, inflammation of the skin (such as 

eczema), sweat gland disorders, ulcers, photosensitivity, acne, hair loss, discoloration, nail 
separation, dry skin and injuries 

 impaired healing 
 kidney and urinary problems including impairment of kidney function, blood in the urine and 

urinary disturbances  
 menstrual cycle (monthly period) disorders including lack of bleeding, or heavy or irregular 

bleeding 
 breast disorders  
 eye and eyelid inflammation, vision disturbances, problems with tears  
 some blood parameters increased (blood alkaline phosphatase increased) 
 prolonged coagulation (clotting) test times 
 
Rare (may affect up to 1 in 1,000 people): 
 gastrointestinal cancer, melanoma 
 lung inflammation (interstitial lung disease, pneumonitis) 
 stroke, blockage in blood vessels (arteriosclerosis), poor blood circulation which makes the toes 

and fingers numb and pale (Raynaud’s phenomenon), mottled purplish skin discoloration, small 
veins near the surface of the skin may become visible 

 pericardial inflammation 
 cardiac arrhythmia 
 enlarged spleen 
 increase of red cell mass 
 white blood cell morphology abnormal 
 formation of stones in the gall bladder 
 kidney problems (including nephritis) 
 immune disorders such as sarcoidosis (rash, joint pain, fever), serum sickness, inflammation of 

the fat tissue, angioneurotic oedema (swelling of the lips, face, throat) 
 thyroid disorders (goitre, tiredness, weight loss) 
 increased iron levels in the body 
 increased blood levels of uric acid 
 suicide attempt, mental impairment, delirium 
 inflammation of the nerves for hearing, seeing, or of the face, impaired coordination or balance 
 increased gastrointestinal motility 
 fistula (tract from one organ to another) (any site) 
 oral disorders including pain on swallowing 
 skin sloughing, blistering, hair texture disorder 
 sexual dysfunction 
 seizure 
 worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle 

weakness) 
 Stevens-Johnson syndrome (a serious skin condition which early symptoms include malaise, 

fever, headache and rash) 
 inflammatory skin rash (erythema multiforme) 
 lichenoid reactions (itchy reddish-purple skin rash and/or threadlike white-grey lines on mucous 

membranes) 
 



156 

Not known (frequency cannot be estimated from the available data): 
 multiple sclerosis* 
 Guillain-Barré syndrome* 
 Merkel cell carcinoma (a type of skin cancer)* 
 Kaposi’s sarcoma (a rare cancer related to infection with human herpes virus 8. Kaposi’s 

sarcoma most commonly appears as purple lesions on the skin) 
 
*These events have been related to this class of medicines but the incidence with Cimzia is not known. 
 
Other side effects 
When Cimzia has been used to treat other diseases the following uncommon side effects have 
occurred: 
 gastrointestinal stenosis (narrowing of part of the digestive system). 
 gastrointestinal obstructions (blockages of the digestive system). 
 general physical health deterioration. 
 spontaneous abortion. 
 azoospermia (lack of sperm production). 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. 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 Cimzia 
 
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 pack and syringe after EXP. The 
expiry date refers to the last day of that month. 
 
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. 
The pre-filled syringes may be stored at room temperature (up to 25°C) for a single period of 
maximum 10 days with protection from light. At the end of this period the pre-filled syringes must be 
used or discarded. 
 
Do not use this medicine if the solution is discoloured, cloudy or if you can see particles in it. 
 
Do not throw away any medicines via wastewater or household waste. Ask your 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 Cimzia contains  
 The active substance is certolizumab pegol. Each pre-filled syringe contains 200 mg of 

certolizumab pegol in one ml. 
 The other ingredients are: sodium acetate, sodium chloride and water for njection (see “Cimzia 

contains sodium acetate and sodium chloride” in section 2). 
 
What Cimzia looks like and contents of the pack 
Cimzia is provided as a solution for injection in a ready to use pre-filled syringe. The solution is clear 
to opalescent, colourless to yellow. 



157 

 
One Cimzia pack contains: 
 two pre-filled syringes with needle guard of solution, and 
 two alcohol wipes (for cleansing the areas chosen for injection). 
 
Pack of 2 pre-filled syringes and 2 alcohol wipes. 
 
Marketing Authorisation Holder 
UCB Pharma S.A.        
Allée de la Recherche 60       
B-1070 Bruxelles        
Belgium         
 
Manufacturer 
UCB Pharma S.A. 
Chemin du Foriest 
B-1420 Braine l'Alleud 
Belgium 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

België/Belgique/Belgien 
UCB Pharma S.A./NV 
Tel/Tél: + 32 / (0)2 559 92 00 
 

Lietuva 
UCB Pharma Oy Finland 
Tel: + 358 9 25144221 

България 
Ю СИ БИ България ЕООД 
Teл.: + 359 (0) 2 962 30 49 

Luxembourg/Luxemburg 
UCB Pharma S.A./NV 
Tél/Tel: + 32 / (0)2 559 92 00 
 

Česká republika 
UCB s.r.o. 
Tel: + 420 221 773 411 

Magyarország 
UCB Magyarország Kft. 
Tel.: + 36-(1) 391 0060 
 

Danmark 
UCB Nordic A/S 
Tlf: + 45 / 32 46 24 00 

Malta 
Pharmasud Ltd. 
Tel: + 356 / 21 37 64 36 
 

Deutschland 
UCB Pharma GmbH 
Tel: + 49 /(0) 2173 48 4848 

Nederland 
UCB Pharma B.V. 
Tel.: + 31 / (0)76-573 11 40 
 

Eesti 
UCB Pharma Oy Finland 
Tel: + 358 9 25144221 

Norge 
UCB Nordic A/S 
Tlf: + 45 / 32 46 24 00 
 

Ελλάδα 
UCB Α.Ε.  
Τηλ: + 30 / 2109974000 

Österreich 
UCB Pharma GmbH 
Tel: + 43-(0) 1 291 80 00 
 

España 
UCB Pharma S.A. 
Tel: + 34 / 91 570 34 44 

Polska 
UCB Pharma Sp. z o.o. 
Tel.: + 48 22 696 99 20 
 



158 

France 
UCB Pharma S.A. 
Tél: + 33 / (0)1 47 29 44 35 

Portugal 
UCB Pharma (Produtos Farmacêuticos), Lda 
Tel: + 351 / 21 302 5300 
 

Hrvatska 
Medis Adria d.o.o. 
Tel: +385 (0) 1 230 34 46 
 

România 
UCB Pharma Romania S.R.L. 
Tel: + 40 21 300 29 04 
 

Ireland 
UCB (Pharma) Ireland Ltd. 
Tel: + 353 / (0)1-46 37 395 

Slovenija 
Medis, d.o.o. 
Tel: + 386 1 589 69 00 
 

Ísland 
Vistor hf. 
Tel: + 354 535 7000 

Slovenská republika 
UCB s.r.o., organizačná zložka 
Tel: + 421 (0) 2 5920 2020 
 

Italia 
UCB Pharma S.p.A. 
Tel: + 39 / 02 300 791 

Suomi/Finland 
UCB Pharma Oy Finland 
Puh/Tel: + 358 9 25144221 
 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Τηλ: + 357 22 34 74 40 

Sverige 
UCB Nordic A/S 
Tel: + 46 / (0) 40 29 49 00 
 

Latvija 
UCB Pharma Oy Finland 
Tel: + 358 9 25144221 

United Kingdom 
UCB Pharma Ltd. 
Tel : + 44 / (0)1753 534 655 
 

 
 
This leaflet was last revised in {MM/YYYY}  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu  
 
------------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for medical or healthcare professionals only: 
INSTRUCTIONS FOR USE FOR THE CIMZIA INJECTION BY MEANS OF A PRE-FILLED 
SYRINGE WITH NEEDLE GUARD 
 
The following instructions explain how to inject Cimzia. Please read the instructions carefully and 
follow them step by step.  
 
This injection should not be mixed in the same syringe with any other medicine. 
 
Below is a diagram of the pre-filled syringe with needle guard. 
 
 



159 

 
Figure 1  

 
1: Needle cap 

2: Plunger head 
3: Needle guard activation clips 

 
For each injection you will need: 
• 1 pre-filled syringe with needle guard 
• 1 alcohol wipe 
 
1. Setting up 
• Remove the Cimzia pack from the refrigerator. 

– If the seal(s) is missing or broken – do not use and contact your pharmacist. 
• Remove the following items from the Cimzia pack and set them up on a clean flat surface: 

– One or two pre-filled syringe(s), depending on your prescriber dose 
– One or two alcohol wipe(s) 

• Look at the expiry date on the pack and dose tray. Do not use Cimzia after the expiry date which 
is stated on the pack and dose tray after EXP. The expiry date refers to the last day of the month 
shown. 

• Allow the pre-filled syringe to reach room temperature. This will take 30 minutes. This will 
help reduce discomfort when injecting. 
– Do not heat the medication - let it warm up on its own. 

• Remove the prefilled syringe from the dose tray by grasping the syringe body as shown in 
Figure 2. Do NOT touch the needle guard activation clips (labelled as 3 in Figure 1) during 
removal (as shown in Figure 3) in order to prevent prematurely covering the needle with 
the needle guard. 

 

  
 Figure 2  Figure 3 

 
 
• Do not use the syringe if it has been dropped without its packaging. 
• Do not remove the cap until you are ready to inject. 



160 

• Wash your hands thoroughly. 
 
2. Choosing and preparing an injection site 
• Choose a site on the thigh or abdomen. 
• Each new injection should be given on a separate site from the last injection site. 

 Do not inject in an area where the skin is reddened, bruised, or hard. 
 Wipe the injection site with the enclosed alcohol wipe, using a circular motion moving 

from the inside out. 
 Do not touch this area again before injection. 
 Do not inject until the skin is dry. 

 
3. Injection 
• Do not shake the syringe. 

Check the medicine in the body of the syringe.  
 Do not use if the solution is discoloured, cloudy or if you can see particles in it. 
  You may see some air bubbles - this is normal. Injecting the solution subcutaneously 

with air bubbles is harmless. 
• Remove the needle cap from the needle by pulling off in a straight line. Take care not to touch 

the needle or let the needle touch any surface. Do NOT touch the needle guard activation 
clips (labelled as 3 in Figure 1) during removal in order to prevent prematurely covering 
the needle with the needle guard. Inject within 5 minutes of removing the needle cap. 

 

 
 

• Gently grasp the cleaned area of skin with one hand and hold firmly. 
• With the other hand, hold syringe at a 45-degree angle to skin. 
• With one quick, short motion, push the needle all the way into the skin. 
 

 
• Release the skin with the first hand. 
• Push plunger head all the way down until the entire dose has been given and the plunger head is 

between the needle guard activation clips. It can take up to 10 seconds to empty the syringe. 



161 

 

 
     

• When the syringe is empty, carefully remove the needle from the skin at the same angle at 
which it was inserted. 

• Take your thumb off the plunger head. The empty syringe and needle will automatically move 
back into the barrel and lock in place. 

• The needle safety device will not activate unless the entire dose is given. 

 
 

• Use a piece of gauze to apply pressure over the injection site for a few seconds: 
 Do not rub the injection site. 
 You may cover the injection site with a small adhesive bandage, if necessary. 

 
4. After Use 
• Do not re-use the syringe.  
• Any unused product(s) or waste material should be disposed of in accordance with local 

requirements. 
• If a second injection is needed as prescribed by the doctor repeat the injection process starting at 

Step 2. 



162 

Package leaflet: Information for the user 
 

Cimzia 200 mg solution for injection in pre-filled pen 
certolizumab pegol 

 
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. 
- If you have any further questions, please ask your doctor, pharmacist or nurse. 
- 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, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Cimzia is and for what it is used for 
2. What you need to know before you use Cimzia 
3. How to use Cimzia 
4. Possible side effects 
5. How to store Cimzia 
6. Contents of the pack and other information 
 
Your physician will also give you a Patient Reminder Card, which contains important safety information 
of which you need to be aware before you are given Cimzia and during treatment with Cimzia. Keep 
this Patient Reminder Card with you. 
 
 
1. What Cimzia is and what it is used for 
 
Cimzia contains the active substance certolizumab pegol, a human antibody fragment. Antibodies are 
proteins that specifically recognise and bind to other proteins. Cimzia binds to a specific protein called 
tumour necrosis factor α (TNFα). Thereby this TNFα is blocked by Cimzia and this decreases 
inflammation diseases such as in rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis and 
psoriasis. Medicines that bind to TNFα are also called TNF blockers. 
 
Cimzia is used in adults for the following inflammatory diseases:  
 rheumatoid arthritis, 
 axial spondyloarthritis (including ankylosing spondylitis and axial spondyloarthritis without 

radiographic evidence of ankylosing spondylitis), 
 psoriatic arthritis, 
 plaque psoriasis 
 
Rheumatoid arthritis 
Cimzia is used to treat rheumatoid arthritis. Rheumatoid arthritis is an inflammatory disease of the 
joints. If you have moderate to severe active rheumatoid arthritis, you may first be given other 
medicines usually methotrexate. If you do not respond well enough to these medicines, you will be 
given Cimzia in combination with methotrexate to treat your rheumatoid arthritis. If your doctor 
determines that methotrexate is inappropriate, Cimzia can be given alone. 
 
Cimzia in combination with methotrexate can also be used to treat severe, active and progressive 
rheumatoid arthritis without previous use of methotrexate or other medicines. 
 
Cimzia, which you will take in combination with methotrexate, is used to: 
 reduce the signs and symptoms of your disease, 
 slow down the damage to the cartilage and bone of the joints caused by the disease, 
 improve your physical function and performance of daily tasks. 



163 

 
Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing 
spondylitis 
Cimzia is used to treat severe active ankylosing spondylitis and axial spondyloarthritis without 
radiographic evidence of ankylosing spondylitis (sometimes referred to as non-radiographic axial 
spondyloarthritis). These diseases are inflammatory diseases of the spine. If you have ankylosing 
spondylitis or non-radiographic axial spondyloarthritis you will first be given other medicines. If you 
do not respond well enough to these medicines, you will be given Cimzia to: 
 reduce the signs and symptoms of your disease, 
 improve your physical function and performance of daily tasks. 
 
Psoriatic arthritis 
Cimzia is used to treat active psoriatic arthritis. Psoriatic arthritis is an inflammatory disease of the 
joints, usually accompanied by psoriasis. If you have active psoriatic arthritis you will first be given 
other medicines, usually methotrexate. If you do not respond well enough to these medicines, you will 
be given Cimzia in combination with methotrexate to: 

 reduce the signs and symptoms of your disease, 
 improve your physical function and performance of daily tasks. 

If your doctor determines that methotrexate is inappropriate, Cimzia can be given alone. 
 
Plaque psoriasis 
Cimzia is used to treat moderate to severe plaque psoriasis. Plaque psoriasis is an inflammatory 
disease of the skin, and can also affect your scalp and nails.  
Cimzia is used to reduce skin inflammation and other signs and symptoms of your disease. 
 
 
2. What you need to know before you use Cimzia 
 
Do NOT use Cimzia 
- If you are ALLERGIC (hypersensitive) to certolizumab pegol or any of the other ingredients of 

this medicine (listed in section 6) 
- If you have a severe infection, including active TUBERCULOSIS (TB). 
- If you have moderate to severe HEART FAILURE. Tell your doctor if you have had or have a 

serious heart condition. 
 
Warnings and precautions 
 
Tell your doctor before treatment with Cimzia if any of the following applies to you: 
 
Allergic reactions 
- If you experience ALLERGIC REACTIONS such as chest tightness, wheezing, dizziness, 

swelling or rash, stop using Cimzia and contact your doctor IMMEDIATELY. Some of these 
reactions could occur after the first administration of Cimzia. 

-  If you have ever had an allergic reaction to latex. 
 
Infections 
- If you have had RECURRENT or OPPORTUNISTIC INFECTIONS or other conditions that 

increase the risk of infections (such as treatment with immunosuppressants, which are 
medicines that could reduce your ability to fight infections). 

- If you have an infection or if you develop symptoms such as fever, wounds, tiredness or dental 
problems. You might get an infection more easily while you are being treated with Cimzia, 
including serious, or in rare cases, life-threatening infections. 

- TUBERCULOSIS (TB) cases have been reported in patients treated with Cimzia, your doctor 
will check you for signs and symptoms of tuberculosis before starting Cimzia. This will include 
a thorough medical history, a chest X-ray and a tuberculin test. The conduct of these tests 
should be recorded on your Patient Reminder Card. If latent (inactive) tuberculosis is diagnosed, 
you might be required to receive appropriate anti-tuberculosis medicines before starting Cimzia. 



164 

In rare occasions tuberculosis can develop during therapy even if you have received preventive 
treatment for tuberculosis. It is very important that you tell your doctor if you have ever had 
tuberculosis, or if you have been in close contact with someone who has had tuberculosis. If 
symptoms of tuberculosis (persistent cough, weight loss, listlessness, mild fever), or any other 
infection appear during or after therapy with Cimzia tell your doctor immediately. 

- If you are at risk of or are a carrier of or have active HEPATITIS B VIRUS (HBV) infection, 
Cimzia may increase the risk of reactivation in people who carry this virus. If this occurs, you 
should stop using Cimzia. Your doctor should test you for HBV before starting Cimzia. 

 
Heart failure 
- If you have mild HEART FAILURE and you are being treated with Cimzia, your heart failure 

status must be closely monitored by your doctor. It is important to tell your doctor if you have 
had or have a serious heart condition. If you develop new or worsening symptoms of heart 
failure (e.g. shortness of breath or swelling of your feet), you must contact your doctor 
immediately. Your doctor may decide to stop treatment with Cimzia. 

 
Cancer 
- It is uncommon, but cases of certain types of CANCER have been reported in patients treated 

with Cimzia or other TNF blockers. People with more severe rheumatoid arthritis that have had 
the disease for a long time may have a higher than average risk of getting a kind of cancer that 
affects the lymph system, called lymphoma. If you take Cimzia, your risk of getting lymphoma 
or other cancers may increase. In addition, uncommon cases of non-melanoma skin cancer have 
been observed in patients taking Cimzia. If new skin lesions appear during or after therapy with 
Cimzia or existing skin lesions change appearance, tell your doctor.  

- There have been cases of cancers, including unusual types, in children and teenage patients 
taking TNF-blocking agents, which sometimes resulted in death (see further down “Children 
and adolescents”). 

 
Other disorders 
- Patients with chronic obstructive pulmonary disease (COPD), or who are heavy smokers, may 

be at increased risk for cancer with Cimzia treatment. If you have COPD or are a heavy smoker, 
you should discuss with your doctor whether treatment with a TNF blocker is appropriate for 
you. 

- If you have a nervous system disorder, such as multiple sclerosis, your doctor will decide 
whether you should use Cimzia. 

- In some patients the body may fail to produce enough of the blood cells that help your body 
fight infections or help you to stop bleeding. If you develop a fever that does not go away, 
bruise or bleed very easily or look very pale, call your doctor immediately. Your doctor may 
decide to stop treatment with Cimzia. 

- It is uncommon, but symptoms of a disease called lupus (for example persistent rash, fever, joint 
pain and tiredness) may occur. If you experience these symptoms, contact your doctor. Your 
doctor may decide to stop treatment with Cimzia. 

 
Vaccinations 
- Talk to your doctor if you have had, or are due to have a vaccine. You should not receive certain 

(live) vaccines while using Cimzia. 
- Certain vaccinations may cause infections. If you received Cimzia while you were pregnant, 

your baby may be at higher risk for getting such an infection for up to approximately five 
months after the last dose you received during pregnancy. It is important that you tell your 
baby's doctors and other health care professionals about your Cimza use so they can decide 
when your baby should receive any vaccine. 

 
Operations or dental procedures 
- Talk to your doctor if you are going to have any operations or dental procedures. Tell your 

surgeon or dentist performing the procedure that you are having treatment with Cimzia by 
showing them your Patient Reminder Card. 

 



165 

Children and adolescents 
Cimzia is not recommended for use in children and adolescents under the age of 18 years. 
 
Other medicines and Cimzia 
You should NOT take Cimzia if you are using the following medicines used to treat rheumatoid 
arthritis: 
- anakinra  
- abatacept 
If you have questions, please ask your doctor. 
 
Cimzia can be taken together with: 
- methotrexate,  
- corticosteroids, or  
- pain medicines including nonsteroidal anti-inflammatory medicines (also called NSAIDs). 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine.  
 
There is limited experience with Cimzia in pregnant women.  
Cimzia should be used during pregnancy only if clearly needed. If you are a woman of childbearing 
potential discuss with your doctor regarding use of adequate contraception while using Cimzia. For 
women planning pregnancy, contraception may be considered for 5 months after the last Cimzia dose. 
 
If you received Cimzia 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 Cimzia use before the baby receives any vaccine (for more information see section on 
vaccinations). 
 
Cimzia can be used during breastfeeding. 
 
Driving and using machines 
Cimzia may have a minor influence on your ability to drive and use machines. Dizziness (including 
room spinning sensation, blurred vision and tiredness) may occur after you take Cimzia. 
 
Cimzia contains sodium acetate and sodium chloride 
This medicinal product contains less than 1 mmol sodium (23 mg) per 400 mg, i.e. essentially 
‘sodium-free’. 
 
 
3. How to use Cimzia 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Rheumatoid arthritis 
 The starting dose for adults with rheumatoid arthritis is 400 mg given at weeks 0, 2 and 4.  
 This is followed by a maintenance dose of 200 mg every 2 weeks. If you respond to the 

medicine, your doctor may prescribe an alternative maintenance dosing of 400 mg 
every 4 weeks.  

 Methotrexate is continued while using Cimzia. If your doctor determines that methotrexate is 
inappropriate, Cimzia can be given alone. 

 



166 

Axial spondyloarthritis 
 The starting dose for adults with axial spondyloarthritis is 400 mg given at weeks 0, 2 and 4.  
 This is followed by a maintenance dose of 200 mg every 2 weeks (from week 6) or 400 mg 

every 4 weeks (from week 8) as instructed by your physician. If you have received Cimzia for at 
least 1 year and respond to the medicine, your physician may prescribe a reduced maintenance 
dose of 200 mg every 4 weeks. 

 
Psoriatic arthritis 
 The starting dose for adults with psoriatic arthritis is 400 mg given at weeks 0, 2 and 4.  
 This is followed by a maintenance dose of 200 mg every 2 weeks. If you respond to the 

medicine, your doctor may prescribe an alternative maintenance dosing of 400 mg 
every 4 weeks.  

 Methotrexate is continued while using Cimzia. If your doctor determines that methotrexate is 
inappropriate, Cimzia can be given alone. 

 
Plaque psoriasis 
 The starting dose for adults with plaque psoriasis is 400 mg every 2 weeks given at 

weeks 0, 2 and 4.  
 This is followed by a maintenance dose of 200 mg every 2 weeks, or 400 mg every 2 weeks as 

instructed by your physician.  
 
How Cimzia is given 
Cimzia will usually be given to you by a specialist doctor or healthcare professional. You will be 

given Cimzia as either one (200 mg dose) or two injections (400 mg dose) under the skin 
(subcutaneous use, abbreviation: SC). It is usually injected into the thigh or tummy. However, 
do not inject in an area where the skin is reddened, bruised, or hard. 

 
Instructions for self-injecting Cimzia 
After suitable training, your doctor may also allow you to inject Cimzia yourself. Please read the 
instructions at the end of this leaflet on how to inject Cimzia. 
 
If your doctor has allowed you to self-inject, you should follow up with your doctor before you 
continue to self-inject: 
 after 12 weeks if you have rheumatoid arthritis, axial spondyloarthritis or psoriatic arthritis, or  
 after 16 weeks if you have plaque psoriasis. 
This is so that the doctor can determine if Cimzia is working for you or if another treatment needs to 
be considered. 
 
If you use more Cimzia than you should 
If your doctor has allowed you to self-inject and you accidentally inject Cimzia more frequently than 
prescribed, you should tell your doctor. Always take the Patient Reminder Card and the outer carton 
from the Cimzia package with you, even if it is empty. 
 
If you forget to use Cimzia 
If your doctor has allowed you to self-inject and you forget to give yourself an injection, you should 
inject the next dose of Cimzia as soon as you remember. Then, talk to your doctor and inject the 
following doses as instructed. 
 
If you stop using Cimzia 
Do not stop using Cimzia without talking to your doctor first. 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 



167 

Tell your doctor IMMEDIATELY if you notice any of the following side effects: 
 severe rash, hives or other signs of allergic reaction (urticaria) 
 swollen face, hands, feet (angioedema) 
 trouble breathing, swallowing (multiple causes for these symptoms) 
 shortness of breath with exertion or upon lying down or swelling of the feet (heart failure) 
 symptoms of blood disorders such as persistent fever, bruising, bleeding, paleness 

(pancytopaenia, anaemia, low platelet count, low white blood cell count) 
 serious skin rashes. These can appear as reddish target-like macules or circular patches often 

with central blisters on the trunk, skin peeling, ulcers of mouth, throat, nose, genitals and eyes 
and can be preceded by fever and flu-like symptoms. (Stevens-Johnson syndrome) 

 
Tell your doctor AS SOON AS POSSIBLE if you notice any of the following side effects: 
 signs of infection such as fever, malaise, wounds, dental problems, burning on urination  
 feeling weak or tired 
 coughing 
 tingling 
 numbness 
 double vision 
 arm or leg weakness 
 bump or open sore that doesn't heal 
 
The symptoms described above can be due to some of the side effects listed below, which have been 
observed with Cimzia: 
 
Common (may affect up to 1 in 10 people): 
 bacterial infections in any site (a collection of pus) 
 viral infections (including cold sores, shingles, and influenza) 
 fever 
 high blood pressure 
 rash or itching  
 headaches (including migraines) 
 sensory abnormalities such as numbness, tingling, burning sensation 
 feeling weak and generally unwell  
 pain 
 blood disorders 
 liver problems 
 injection site reactions 
 nausea 
 
Uncommon (may affect up to 1 in 100 people): 
 allergic conditions including allergic rhinitis and allergic reactions to the medicine (including 

anaphylactic shock) 
 antibody directed against normal tissue 
 blood and lymphatic system cancers like lymphoma and leukaemia 
 solid organ cancers 
 skin cancers, pre-cancerous skin lesions 
 benign (non-cancerous) tumours and cysts (including those of the skin) 
 heart problems including weakened heart muscle, heart failure, heart attack, chest discomfort or 

chest pressure, abnormal heart rhythm including irregular heart beats 
 oedema (swelling in the face or legs) 
 lupus (immune/connective tissue disease) symptoms (joint pain, skin rashes, photosensitivity 

and fever)  
 inflammation of the blood vessels 
 sepsis (serious infection which can result in organ failure, shock or death) 
 tuberculosis infection 



168 

 fungal infections (occur when the ability to fight off infection is lessened) 
 respiratory disorders and inflammation (including asthma, shortness of breath, cough, blocked 

sinuses, pleurisy, or difficulty breathing) 
 stomach problems including abdominal fluid collection, ulcers (including oral ulcers), 

perforation, distension, inflammation heartburn, upset, dry mouth 
 bile problems 
 muscle problems including increased muscle enzymes 
 changes in blood levels of different salts 
 changes in cholesterol and fat levels in the blood 
 blood clots in the veins or lungs 
 bleeding or bruising 
 changed numbers of blood cells, including low red cell count (anaemia), low platelet counts, 

increased platelet counts 
 swollen lymph nodes 
 flu-like symptoms, chills, altered temperature perception, night sweats, flushing 
 anxiety and mood disorders such as depression, appetite disorders, weight change 
 ringing in the ears  
 vertigo (dizziness) 
 feeling faint, including loss of consciousness 
 nerve disorders in the extremities including symptoms of numbness, tingling, burning sensation, 

dizziness, tremor 
 skin disorders such as new onset or worsening of psoriasis, inflammation of the skin (such as 

eczema), sweat gland disorders, ulcers, photosensitivity, acne, hair loss, discoloration, nail 
separation, dry skin and injuries 

 impaired healing 
 kidney and urinary problems including impairment of kidney function, blood in the urine and 

urinary disturbances  
 menstrual cycle (monthly period) disorders including lack of bleeding, or heavy or irregular 

bleeding 
 breast disorders  
 eye and eyelid inflammation, vision disturbances, problems with tears  
 some blood parameters increased (blood alkaline phosphatase increased) 
 prolonged coagulation (clotting) test times 
 
Rare (may affect up to 1 in 1,000 people): 
 gastrointestinal cancer, melanoma 
 lung inflammation (interstitial lung disease, pneumonitis) 
 stroke, blockage in blood vessels (arteriosclerosis), poor blood circulation which makes the toes 

and fingers numb and pale (Raynaud’s phenomenon), mottled purplish skin discoloration, small 
veins near the surface of the skin may become visible 

 pericardial inflammation 
 cardiac arrhythmia 
 enlarged spleen 
 increase of red cell mass 
 white blood cell morphology abnormal 
 formation of stones in the gall bladder 
 kidney problems (including nephritis) 
 immune disorders such as sarcoidosis (rash, joint pain, fever), serum sickness, inflammation of 

the fat tissue, angioneurotic oedema (swelling of the lips, face, throat) 
 thyroid disorders (goitre, tiredness, weight loss) 
 increased iron levels in the body 
 increased blood levels of uric acid  
 suicide attempt, mental impairment, delirium 
 inflammation of the nerves for hearing, seeing, or of the face, impaired coordination or balance 



169 

 increased gastrointestinal motility 
 fistula (tract from one organ to another) (any site) 
 oral disorders including pain on swallowing 
 skin sloughing, blistering, hair texture disorder 
 sexual dysfunction 
 seizure 
 worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle 

weakness) 
 Stevens-Johnson syndrome (a serious skin condition which early symptoms include malaise, 

fever, headache and rash) 
 inflammatory skin rash (erythema multiforme) 
 lichenoid reactions (itchy reddish-purple skin rash and/or threadlike white-grey lines on mucous 

membranes) 
 
Not known (frequency cannot be estimated from the available data): 
 multiple sclerosis* 
 Guillain-Barré syndrome* 
 Merkel cell carcinoma (a type of skin cancer)* 
 Kaposi’s sarcoma (a rare cancer related to infection with human herpes virus 8. Kaposi’s 

sarcoma most commonly appears as purple lesions on the skin) 
 
*These events have been related to this class of medicines but the incidence with Cimzia is not known. 
 
Other side effects 
When Cimzia has been used to treat other diseases the following uncommon side effects have 
occurred: 
 gastrointestinal stenosis (narrowing of part of the digestive system). 
 gastrointestinal obstructions (blockages of the digestive system). 
 general physical health deterioration. 
 spontaneous abortion. 
 azoospermia (lack of sperm production). 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. 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 Cimzia 
 
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 pack and pen after EXP. The 
expiry date refers to the last day of that month. 
 
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. 
The pre-filled pens may be stored at room temperature (up to 25°C) for a single period of 
maximum 10 days with protection from light. At the end of this period the pre-filled pens must be 
used or discarded. 
 
Do not use this medicine if the solution is discoloured, cloudy or if you can see particles in it.  
 



170 

Do not throw away any medicines via wastewater or household waste. Ask your 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 Cimzia contains  
 The active substance is certolizumab pegol. Each pre-filled pen contains 200 mg of 

certolizumab pegol in one ml. 
 The other ingredients are: sodium acetate, sodium chloride and water for injection (see “Cimzia 

contains sodium acetate and sodium chloride” in section 2). 
 
What Cimzia looks like and contents of the pack 
Cimzia is provided as a solution for injection in a ready to use pre-filled pen (AutoClicks). The 
solution is clear to opalescent, colourless to yellow. 
 
One Cimzia pack contains: 
 two AutoClicks pre-filled pens of solution, and 
 two alcohol wipes (for cleansing the areas chosen for injection). 
 
Packs of 2 pre-filled pens and 2 alcohol wipes, a multipack containing 6 (3 packs of 2) pre-filled pens 
and 6 (3 packs of 2) alcohol wipes, and a multipack containing 10 (5 packs of 2) pre-filled pens 
and 10 (5 packs of 2) alcohol wipes are available. 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder  
UCB Pharma S.A.        
Allée de la Recherche 60       
B-1070 Bruxelles        
Belgium         
 
Manufacturer 
UCB Pharma S.A. 
Chemin du Foriest 
B-1420 Braine l'Alleud 
Belgium 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

België/Belgique/Belgien 
UCB Pharma S.A./NV 
Tel/Tél: + 32 / (0)2 559 92 00 
 

Lietuva 
UCB Pharma Oy Finland 
Tel: + 358 9 25144221 

България 
Ю СИ БИ България ЕООД 
Teл.: + 359 (0) 2 962 30 49 

Luxembourg/Luxemburg 
UCB Pharma S.A./NV 
Tél/Tel: + 32 / (0)2 559 92 00 
 

Česká republika 
UCB s.r.o. 
Tel: + 420 221 773 411 

Magyarország 
UCB Magyarország Kft. 
Tel.: + 36-(1) 391 0060 
 

Danmark 
UCB Nordic A/S 
Tlf: + 45 / 32 46 24 00 

Malta 
Pharmasud Ltd. 
Tel: + 356 / 21 37 64 36 
 



171 

Deutschland 
UCB Pharma GmbH 
Tel: + 49 /(0) 2173 48 4848 

Nederland 
UCB Pharma B.V. 
Tel.: + 31 / (0)76-573 11 40 
 

Eesti 
UCB Pharma Oy Finland 
Tel: + 358 9 25144221 

Norge 
UCB Nordic A/S 
Tlf: + 45 / 32 46 24 00 
 

Ελλάδα 
UCB Α.Ε.  
Τηλ: + 30 / 2109974000 

Österreich 
UCB Pharma GmbH 
Tel: + 43-(0)1 291 80 00 
 

España 
UCB Pharma S.A. 
Tel: + 34 / 91 570 34 44 

Polska 
UCB Pharma Sp. z o.o. 
Tel.: + 48 22 696 99 20 
 

France 
UCB Pharma S.A. 
Tél: + 33 / (0)1 47 29 44 35 

Portugal 
UCB Pharma (Produtos Farmacêuticos), Lda 
Tel: + 351 / 21 302 5300 
 

Hrvatska 
Medis Adria d.o.o. 
Tel: +385 (0) 1 230 34 46 
 

România 
UCB Pharma Romania S.R.L. 
Tel: + 40 21 300 29 04 
 

Ireland 
UCB (Pharma) Ireland Ltd. 
Tel: + 353 / (0)1-46 37 395 

Slovenija 
Medis, d.o.o. 
Tel: + 386 1 589 69 00 
 

Ísland 
Vistor hf. 
Tel: + 354 535 7000 

Slovenská republika 
UCB s.r.o., organizačná zložka 
Tel: + 421 (0) 2 5920 2020 
 

Italia 
UCB Pharma S.p.A. 
Tel: + 39 / 02 300 791 

Suomi/Finland 
UCB Pharma Oy Finland 
Puh/Tel: + 358 9 25144221 
 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Τηλ: + 357 22 34 74 40 
 

Sverige 
UCB Nordic A/S 
Tel: + 46 / (0) 40 29 49 00 
 

Latvija 
UCB Pharma Oy Finland 
Tel: + 358 9 25144221 
 

United Kingdom 
UCB Pharma Ltd. 
Tel : + 44 / (0)1753 534 655 
 

 
This leaflet was last revised in {MM/YYYY}  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu  
 
--------------------------------------------------------------------------------------------------------------------------- 
 



172 

INSTRUCTIONS FOR USE FOR THE CIMZIA INJECTION BY MEANS OF PRE-FILLED 
PEN 
After proper training, the injection can be self-administered or given by another person, for example a 
family member or friend. The following instructions explain how to use the pre-filled pen 
(AutoClicks) to inject Cimzia. Please read the instructions carefully and follow them step by step. You 
will be instructed by your doctor or healthcare giver on the technique of self-injection. Do not attempt 
to self-inject until you are sure that you understand how to prepare and give the injection.  
 
Below is a diagram of the AutoClicks pre-filled pen. 
 

 
 

1: Orange band 
2: Viewing window 

3: Black handle 
4: Clear cap 

 
1. Setting up 
 Remove the Cimzia pack from the refrigerator. 

– If the seal(s) is missing or broken – do not use and contact your pharmacist. 
 Remove the following items from the Cimzia pack and set them up on a clean flat surface: 

◦ One or two AutoClicks pre-filled pen(s), depending on your prescribed dose 
◦ One or two alcohol wipe(s) 

 Look at the expiry date on the pre-filled pen and pack. Do not use Cimzia after the expiry date 
which is stated on the pack and pre-filled pen after EXP. The expiry date refers to the last day of 
the month shown. 

 Allow the AutoClicks pre filled pen(s) to reach room temperature. This will 
take 30 to 45 minutes. This will help to reduce discomfort when injecting. 
 Do not heat the medication - let it warm up on its own 
 Do not remove the cap until you are ready to inject. 

 
 Wash your hands thoroughly. 
 
2. Choosing and preparing an injection site 
 Choose a site on your thigh or tummy. 



173 

 
 Each new injection should be given on a separate site from the last injection site. 

 Do not inject in an area where the skin is reddened, bruised, or hard.  
 Wipe the injection site with the enclosed alcohol wipe, using a circular motion moving 

from the inside out. 
 Do not touch the area again before injecting. 

 
3. Injection 
 AutoClicks pre-filled pen is designed to work accurately and safely. However, if any of the 

following steps go wrong and/or if you feel unsure about the injection process, contact your 
doctor or pharmacist. 

 Do not shake the pre-filled pen.  

Check the medicine through the viewing window.  
 Do not use the pre-filled pen if the solution is discoloured, cloudy or if you can see 

particles in it. 
 You may see air bubbles - this is normal. Injecting the solution subcutaneously which 

contains air bubbles is harmless. 

 
 Hold the pre-filled pen firmly with one hand around the black handle. 
 Grasp the clear cap with the other hand and pull it straight off. Do not twist the cap while 

removing it, this could jam the internal mechanism. 
 

  

 
• Inject within 5 minutes of removing the cap. Do not replace the cap. 



174 

• Although hidden from view the needle tip is now uncovered. Do not try to touch the needle as it 
could activate the pre-filled pen. Hold the pre-filled pen straight (at a 90° degree angle) against 
the skin, that previously has been cleaned (the “injection site”). 

 

 
 

• Press the pre-filled pen firmly against the skin. The injection begins when a first “click” is heard 
and the orange band at the bottom of the pre-filled pen disappears. 

 
 Continue to hold the pre-filled pen in place firmly against the skin until a second “click” is 

heard and the viewing window turns orange. This can take up to 15 seconds. At this time, the 
injection will be complete. If the viewing window turns orange and you hear a second click this 
means the injection has been completed. If you feel unsure about the injection process, please 
contact your doctor or pharmacist. Do not try to repeat the injection process without speaking to 
your doctor or your pharmacist. 

 

 
• The needle will automatically move back into the empty pen. Do not try to touch the needle. 
• You can now remove the used pen by pulling the pen straight up carefully from the skin. 
• Use a piece of gauze, apply pressure over the injection site for a few seconds: 

 Do not rub the injection site.  
 You may cover the injection site with a small adhesive bandage, if necessary. 

 
4. After Use 
• Do not re-use the pen. There is no need to replace the cap. 



175 

• After injection, immediately throw away the used pen(s) in a special container as instructed by 
your doctor, nurse or pharmacist. 

 
 

• Keep the container out of the sight and reach of children. 
• If you need to have a second injection as prescribed by your doctor repeat the injection process 

starting at Step 2. 



176 

Package leaflet: Information for the user 
 

Cimzia 200 mg solution for injection in dose-dispenser cartridge 
certolizumab pegol 

 
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. 
- If you have any further questions, please ask your doctor, pharmacist or nurse. 
- 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, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Cimzia is and what it is used for 
2. What you need to know before you use Cimzia 
3. How to use Cimzia 
4. Possible side effects 
5. How to store Cimzia 
6. Contents of the pack and other information 
 
Your physician will also give you a Patient Reminder Card, which contains important safety information 
of which you need to be aware before you are given Cimzia and during treatment with Cimzia. Keep 
this Patient Reminder Card with you. 
 
 
1. What Cimzia is and what it is used for 
 
Cimzia contains the active substance certolizumab pegol, a human antibody fragment. Antibodies are 
proteins that specifically recognise and bind to other proteins. Cimzia binds to a specific protein called 
tumour necrosis factor α (TNFα). Thereby this TNFα is blocked by Cimzia and this decreases 
inflammation diseases such as in rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis and 
psoriasis. Medicines that bind to TNFα are also called TNF blockers. 
 
Cimzia is used in adults for the following inflammatory diseases:  
 rheumatoid arthritis, 
 axial spondyloarthritis (including ankylosing spondylitis and axial spondyloarthritis without 

radiographic evidence of ankylosing spondylitis), 
 psoriatic arthritis, 
 plaque psoriasis 
 
Rheumatoid arthritis 
Cimzia is used to treat rheumatoid arthritis. Rheumatoid arthritis is an inflammatory disease of the 
joints. If you have moderate to severe active rheumatoid arthritis, you may first be given other 
medicines usually methotrexate. If you do not respond well enough to these medicines, you will be 
given Cimzia in combination with methotrexate to treat your rheumatoid arthritis. If your doctor 
determines that methotrexate is inappropriate, Cimzia can be given alone. 
 
Cimzia in combination with methotrexate can also be used to treat severe, active and progressive 
rheumatoid arthritis without previous use of methotrexate or other medicines treatment. 
 
Cimzia, which you will take in combination with methotrexate, is used to: 
 reduce the signs and symptoms of your disease, 
 slow down the damage to the cartilage and bone of the joints caused by the disease, 
 improve your physical function and performance of daily tasks. 
 



177 

Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing 
spondylitis 
Cimzia is used to treat severe active ankylosing spondylitis and axial spondyloarthritis without 
radiographic evidence of ankylosing spondylitis (sometimes referred to as non-radiographic axial 
spondyloarthritis). These diseases are inflammatory diseases of the spine.  
 
If you have ankylosing spondylitis or non-radiographic axial spondyloarthritis you will first be given 
other medicines. If you do not respond well enough to these medicines, you will be given Cimzia to: 
 reduce the signs and symptoms of your disease, 
 improve your physical function and performance of daily tasks. 
 
Psoriatic arthritis 
Cimzia is used to treat active psoriatic arthritis. Psoriatic arthritis is an inflammatory disease of the 
joints, usually accompanied by psoriasis. If you have active psoriatic arthritis you will first be given 
other medicines, usually methotrexate. If you do not respond well enough to these medicines, you will 
be given Cimzia in combination with methotrexate to: 
 reduce the signs and symptoms of your disease, 
 improve your physical function and performance of daily tasks. 
If your doctor determines that methotrexate is inappropriate, Cimzia can be given alone. 
 
Plaque psoriasis 
Cimzia is used to treat moderate to severe plaque psoriasis. Plaque psoriasis is an inflammatory 
disease of the skin, and can also affect your scalp and nails.  
Cimzia is used to reduce skin inflammation and other signs and symptoms of your disease. 
 
 
2. What you need to know before you use Cimzia 
 
Do NOT use Cimzia:  
- If you are ALLERGIC (hypersensitive) to certolizumab pegol or any of the other ingredients of 

this medicine (listed in section 6) 
- If you have a severe infection, including active TUBERCULOSIS (TB). 
- If you have moderate to severe HEART FAILURE. Tell your doctor if you have had or have a 

serious heart condition. 
 
Warnings and precautions 
Talk to your doctor, pharmacist or nurse before using Cimzia if any of the following applies to you: 
 
Allergic reactions 
- If you experience ALLERGIC REACTIONS such as chest tightness, wheezing, dizziness, 

swelling or rash, stop using Cimzia and contact your doctor IMMEDIATELY. Some of these 
reactions could occur after the first administration of Cimzia. 

-  If you have ever had an allergic reaction to latex. 
 
Infections 
- If you have had RECURRENT or OPPORTUNISTIC INFECTIONS or other conditions that 

increase the risk of infections (such as treatment with immunosuppressants, which are 
medicines that could reduce your ability to fight infections). 

- If you have an infection or if you develop symptoms such as fever, wounds, tiredness or dental 
problems. You might get an infection more easily while you are being treated with Cimzia, 
including serious, or in rare cases, life-threatening infections. 

- TUBERCULOSIS (TB) cases have been reported in patients treated with Cimzia, your doctor 
will check you for signs and symptoms of tuberculosis before starting Cimzia. This will include 
a thorough medical history, a chest X-ray and a tuberculin test. The conduct of these tests 
should be recorded on your Patient Reminder Card. If latent (inactive) tuberculosis is diagnosed, 
you might be required to receive appropriate anti tuberculosis medicines before starting Cimzia. 
In rare occasions tuberculosis can develop during therapy even if you have received preventive 



178 

treatment for tuberculosis. It is very important that you tell your doctor if you have ever had 
tuberculosis, or if you have been in close contact with someone who has had tuberculosis. If 
symptoms of tuberculosis (persistent cough, weight loss, listlessness, mild fever), or any other 
infection appear during or after therapy with Cimzia tell your doctor immediately. 

- If you are at risk of or are a carrier of or have active HEPATITIS B VIRUS (HBV) infection, 
Cimzia may increase the risk of reactivation in people who carry this virus. If this occurs, you 
should stop using Cimzia. Your doctor should test you for HBV before starting Cimzia. 

 
Heart failure 
- If you have mild HEART FAILURE and you are being treated with Cimzia, your heart failure 

status must be closely monitored by your doctor. It is important to tell your doctor if you have 
had or have a serious heart condition. If you develop new or worsening symptoms of heart 
failure (e.g. shortness of breath or swelling of your feet), you must contact your doctor 
immediately. Your doctor may decide to stop treatment with Cimzia. 

 
Cancer 
- It is uncommon, but cases of certain types of CANCER have been reported in patients treated 

with Cimzia or other TNF blockers. People with more severe rheumatoid arthritis that have had 
the disease for a long time may have a higher than average risk of getting a kind of cancer that 
affects the lymph system, called lymphoma. If you take Cimzia, your risk of getting lymphoma 
or other cancers may increase. In addition, uncommon cases of non-melanoma skin cancer have 
been observed in patients taking Cimzia. If new skin lesions appear during or after therapy with 
Cimzia or existing skin lesions change appearance, tell your doctor.  

- There have been cases of cancers, including unusual types, in children and teenage patients 
taking TNF blocking agents, which sometimes resulted in death (see further down “Children 
and adolescents”). 

 
Other disorders 
- Patients with chronic obstructive pulmonary disease (COPD), or who are heavy smokers, may 

be at increased risk for cancer with Cimzia treatment. If you have COPD or are a heavy smoker, 
you should discuss with your doctor whether treatment with a TNF blocker is appropriate for 
you. 

- If you have a nervous system disorder, such as multiple sclerosis, your doctor will decide 
whether you should use Cimzia. 

- In some patients the body may fail to produce enough of the blood cells that help your body 
fight infections or help you to stop bleeding. If you develop a fever that does not go away, 
bruise or bleed very easily or look very pale, call your doctor immediately. Your doctor may 
decide to stop treatment with Cimzia. 

- It is uncommon, but symptoms of a disease called lupus (for example persistent rash, fever, joint 
pain and tiredness) may occur. If you experience these symptoms, contact your doctor. Your 
doctor may decide to stop treatment with Cimzia. 

 
Vaccinations 
- Talk to your doctor if you have had, or are due to have a vaccine. You should not receive certain 

(live) vaccines while using Cimzia. 
- Certain vaccinations may cause infections. If you received Cimzia while you were pregnant, 

your baby may be at higher risk for getting such an infection for up to approximately five 
months after the last dose you received during pregnancy. It is important that you tell your 
baby's doctors and other health care professionals about your Cimza use so they can decide 
when your baby should receive any vaccine. 

 
Operations or dental procedures 
- Talk to your doctor if you are going to have any operations or dental procedures. Tell your 

surgeon or dentist performing the procedure that you are having treatment with Cimzia by 
showing them your Patient Reminder Card. 

 



179 

Children and adolescents 
Cimzia is not recommended for use in children and adolescents under the age of 18 years. 
 
Other medicines and Cimzia 
You should NOT take Cimzia if you are using the following medicines used to treat rheumatoid 
arthritis: 
- anakinra  
- abatacept 
If you have questions, please ask your doctor. 
 
Cimzia can be taken together with: 
- methotrexate,  
- corticosteroids, or  
- pain medicines including nonsteroidal anti-inflammatory medicines (also called NSAIDs). 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
There is limited experience with Cimzia in pregnant women.  
Cimzia should only be used during pregnancy if clearly needed. If you are a woman of childbearing 
potential discuss with your doctor regarding use of adequate contraception while using Cimzia. For 
women planning pregnancy, contraception may be considered for 5 months after the last Cimzia dose. 
 
If you received Cimzia 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 Cimzia use before the baby receives any vaccine (for more information see section on 
vaccinations). 
 
Cimzia can be used during breastfeeding.  
 
Driving and using machines 
Cimzia may have a minor influence on your ability to drive and use machines. Dizziness (including 
room spinning sensation, blurred vision and tiredness) may occur after you take Cimzia. 
 
Cimzia contains sodium acetate and sodium chloride 
This medicinal product contains less than 1 mmol sodium (23 mg) per 400 mg, i.e. essentially 
‘sodium-free’. 
 
 
3. How to use Cimzia 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Rheumatoid arthritis 
 The starting dose for adults with rheumatoid arthritis is 400 mg given at weeks 0, 2 and 4.  
 This is followed by a maintenance dose of 200 mg every 2 weeks. If you respond to the 

medicine, your doctor may prescribe an alternative maintenance dosing of 400 mg 
every 4 weeks.  

 Methotrexate is continued while using Cimzia. If your doctor determines that methotrexate is 
inappropriate, Cimzia can be given alone. 

 



180 

Axial spondyloarthritis 
 The starting dose for adults with axial spondyloarthritis is 400 mg given at weeks 0, 2 and 4.  
 This is followed by a maintenance dose of 200 mg every 2 weeks (from week 6) or 400 mg 

every 4 weeks (from week 8) as instructed by your physician. If you have received Cimzia for at 
least 1 year and respond to the medicine, your physician may prescribe a reduced maintenance 
dose of 200 mg every 4 weeks. 

 
Psoriatic arthritis 
 The starting dose for adults with psoriatic arthritis is 400 mg given at weeks 0, 2 and 4.  
 This is followed by a maintenance dose of 200 mg every 2 weeks. If you respond to the 

medicine, your doctor may prescribe an alternative maintenance dosing of 400 mg 
every 4 weeks.  

 Methotrexate is continued while using Cimzia. If your doctor determines that methotrexate is 
inappropriate, Cimzia can be given alone. 

 
Plaque psoriasis 
 The starting dose for adults with plaque psoriasis is 400 mg every 2 weeks given at 

weeks 0, 2 and 4.  
 This is followed by a maintenance dose of 200 mg every 2 weeks, or 400 mg every 2 weeks as 

instructed by your physician.  
 
How Cimzia is given 
Cimzia will usually be given to you by a specialist doctor or healthcare professional. You will be 
given Cimzia as either one (200 mg dose) or two injections (400 mg dose) under the skin 
(subcutaneous use, abbreviation: SC). It is usually injected into the thigh or tummy. However, do not 
inject in an area where the skin is reddened, bruised, or hard. 
 
Instructions for self-injecting Cimzia 
Cimzia solution for injection in a dose-dispenser cartridge (also referred to as “medication”) is 
intended for single-use in conjunction with the electromechanical injection device called ava. After 
suitable training, your doctor may allow you to inject Cimzia yourself. Please read the instructions at 
the end of this leaflet on how to inject Cimzia and in the user manual provided with the injection 
device ava. Please follow these carefully. 
 
If your doctor has allowed you to self-inject, you should follow up with your doctor before you 
continue to self-inject: 
 after 12 weeks if you have rheumatoid arthritis, axial spondyloarthritis or psoriatic arthritis, or  
 after 16 weeks if you have plaque psoriasis. 
This is so that the doctor can determine if Cimzia is working for you or if another treatment needs to 
be considered. 
 
If you use more Cimzia than you should 
If your doctor has allowed you to self-inject and you accidentally inject Cimzia more frequently than 
prescribed, you should tell your doctor. Always take the Patient Reminder Card and the outer carton 
from the Cimzia package with you, even if it is empty. 
 
If you forget to use Cimzia 
If your doctor has allowed you to self-inject and you forget to give yourself an injection, you should 
inject yourself as soon as you remember and contact your doctor for information. Then, talk to your 
doctor and inject the following doses as instructed.  
 
If you stop using Cimzia 
Do not stop using Cimzia without talking to your doctor first. 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 



181 

4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Tell your doctor IMMEDIATELY if you notice any of the following side effects: 
 severe rash, hives or other signs of allergic reaction (urticaria) 
 swollen face, hands, feet (angioedema) 
 trouble breathing, swallowing (multiple causes for these symptoms) 
 shortness of breath with exertion or upon lying down or swelling of the feet (heart failure) 
 symptoms of blood disorders such as persistent fever, bruising, bleeding, paleness 

(pancytopaenia, anaemia, low platelet count, low white blood cell count) 
 serious skin rashes. These can appear as reddish target-like macules or circular patches often 

with central blisters on the trunk, skin peeling, ulcers of mouth, throat, nose, genitals and eyes 
and can be preceded by fever and flu-like symptoms. (Stevens-Johnson syndrome) 

 
Tell your doctor AS SOON AS POSSIBLE if you notice any of the following side effects: 
 signs of infection such as fever, malaise, wounds, dental problems, burning on urination  
 feeling weak or tired 
 coughing 
 tingling 
 numbness 
 double vision 
 arm or leg weakness 
 bump or open sore that doesn't heal 
 
The symptoms described above can be due to some of the side effects listed below, which have been 
observed with Cimzia: 
 
Common (may affect up to 1 in 10 people): 
 bacterial infections in any site (a collection of pus) 
 viral infections (including cold sores, shingles, and influenza) 
 fever 
 high blood pressure 
 rash or itching  
 headaches (including migraines) 
 sensory abnormalities such as numbness, tingling, burning sensation 
 feeling weak and generally unwell  
 pain 
 blood disorders 
 liver problems 
 injection site reactions 
 nausea 
 
Uncommon (may affect up to 1 in 100 people): 
 allergic conditions including allergic rhinitis and allergic reactions to the medicine (including 

anaphylactic shock) 
 antibody directed against normal tissue 
 blood and lymphatic system cancers like lymphoma and leukaemia 
 solid organ cancers 
 skin cancers, pre-cancerous skin lesions 
 benign (non-cancerous) tumours and cysts (including those of the skin) 
 heart problems including weakened heart muscle, heart failure, heart attack, chest discomfort or 

chest pressure, abnormal heart rhythm including irregular heart beats 
 oedema (swelling in the face or legs) 



182 

 lupus (immune/connective tissue disease) symptoms (joint pain, skin rashes, photosensitivity 
and fever)  

 inflammation of the blood vessels 
 sepsis (serious infection which can result in organ failure, shock or death) 
 tuberculosis infection 
 fungal infections (occur when the ability to fight off infection is lessened) 
 respiratory disorders and inflammation (including asthma, shortness of breath, cough, blocked 

sinuses, pleurisy, or difficulty breathing) 
 stomach problems including abdominal fluid collection, ulcers (including oral ulcers), 

perforation, distension, inflammation heartburn, upset, dry mouth 
 bile problems 
 muscle problems including increased muscle enzymes 
 changes in blood levels of different salts 
 changes in cholesterol and fat levels in the blood 
 blood clots in the veins or lungs 
 bleeding or bruising 
 changed numbers of blood cells, including low red cell count (anaemia), low platelet counts, 

increased platelet counts 
 swollen lymph nodes 
 flu-like symptoms, chills, altered temperature perception, night sweats, flushing 
 anxiety and mood disorders such as depression, appetite disorders, weight change 
 ringing in the ears  
 vertigo (dizziness) 
 feeling faint, including loss of consciousness 
 nerve disorders in the extremities including symptoms of numbness, tingling, burning sensation, 

dizziness, tremor 
 skin disorders such as new onset or worsening of psoriasis, inflammation of the skin (such as 

eczema), sweat gland disorders, ulcers, photosensitivity, acne, hair loss, discoloration, nail 
separation, dry skin and injuries 

 impaired healing 
 kidney and urinary problems including impairment of kidney function, blood in the urine and 

urinary disturbances  
 menstrual cycle (monthly period) disorders including lack of bleeding, or heavy or irregular 

bleeding 
 breast disorders  
 eye and eyelid inflammation, vision disturbances, problems with tears  
 some blood parameters increased (blood alkaline phosphatase increased) 
 prolonged coagulation (clotting) test times 
 
Rare (may affect up to 1 in 1,000 people): 
 gastrointestinal cancer, melanoma 
 lung inflammation (interstitial lung disease, pneumonitis) 
 stroke, blockage in blood vessels (arteriosclerosis), poor blood circulation which makes the toes 

and fingers numb and pale (Raynaud’s phenomenon), mottled purplish skin discoloration, small 
veins near the surface of the skin may become visible 

 pericardial inflammation 
 cardiac arrhythmia 
 enlarged spleen 
 increase of red cell mass 
 white blood cell morphology abnormal 
 formation of stones in the gall bladder 
 kidney problems (including nephritis) 
 immune disorders such as sarcoidosis (rash, joint pain, fever), serum sickness, inflammation of 

the fat tissue, angioneurotic oedema (swelling of the lips, face, throat) 
 thyroid disorders (goitre, tiredness, weight loss) 



183 

 increased iron levels in the body 
 increased blood levels of uric acid  
 suicide attempt, mental impairment, delirium 
 inflammation of the nerves for hearing, seeing, or of the face, impaired coordination or balance 
 increased gastrointestinal motility 
 fistula (tract from one organ to another) (any site) 
 oral disorders including pain on swallowing 
 skin sloughing, blistering, hair texture disorder 
 sexual dysfunction 
 seizure 
 worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle 

weakness) 
 Stevens-Johnson syndrome (a serious skin condition which early symptoms include malaise, 

fever, headache and rash) 
 inflammatory skin rash (erythema multiforme) 
 lichenoid reactions (itchy reddish-purple skin rash and/or threadlike white-grey lines on mucous 

membranes) 
 
Not known (frequency cannot be estimated from the available data): 
 multiple sclerosis* 
 Guillain Barré syndrome* 
 Merkel cell carcinoma (a type of skin cancer)* 
 Kaposi’s sarcoma (a rare cancer related to infection with human herpes virus 8. Kaposi’s 

sarcoma most commonly appears as purple lesions on the skin) 
 
*These events have been related to this class of medicines but the incidence with Cimzia is not known. 
 
Other side effects 
When Cimzia has been used to treat other diseases the following uncommon side effects have 
occurred: 
 gastrointestinal stenosis (narrowing of part of the digestive system). 
 gastrointestinal obstructions (blockages of the digestive system). 
 general physical health deterioration. 
 spontaneous abortion. 
 azoospermia (lack of sperm production). 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. 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 Cimzia 
 
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 pack and dose-dispenser cartridge 
after EXP. The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Keep the dose-dispenser cartridge in the outer carton in order to protect from light. 
The dose-dispenser cartridges may be stored at room temperature (up to 25°C) for a single period of 
maximum 10 days with protection from light. At the end of this period the dose-dispenser cartridges 
must be used or discarded. 



184 

 
Do not use this medicine if the solution is discoloured, cloudy or if you can see particles in it.  
 
Do not throw away any medicines via wastewater or household waste. Ask your 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 Cimzia contains  
 The active substance is certolizumab pegol. Each dose-dispenser cartridge contains 200 mg of 

certolizumab pegol in one ml. 
 The other ingredients are: sodium acetate, sodium chloride and water for injection (see “Cimzia 

contains sodium acetate and sodium chloride” in section 2). 
 
What Cimzia looks like and contents of the pack 
Cimzia is provided as a solution for injection in a ready to use dose-dispenser cartridge. The dose-
dispenser cartridge is to be used with the electromechanical injection device ava. The device is 
provided separately. The solution is clear to opalescent, colourless to yellow. 
 
One Cimzia pack contains: 
 two dose-dispenser cartridges of solution, and 
 two alcohol wipes (for cleansing the areas chosen for injection). 
 
Packs of 2 dose-dispenser cartridges and 2 alcohol wipes, a multipack containing 6 (3 packs of 2) 
dose-dispenser cartridges and 6 (3 packs of 2) alcohol wipes, and a multipack containing 10 (5 packs 
of 2) dose-dispenser cartridges and 10 (5 packs of 2) alcohol wipes are available. 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder  
UCB Pharma S.A.        
Allée de la Recherche 60       
B-1070 Bruxelles        
Belgium         
 
Manufacturer 
UCB Pharma S.A. 
Chemin du Foriest 
B-1420 Braine l'Alleud 
Belgium 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

België/Belgique/Belgien 
UCB Pharma S.A./NV 
Tel/Tél: + 32 / (0)2 559 92 00 
 

Lietuva 
UCB Pharma Oy Finland 
Tel: + 358 9 25144221 

България 
Ю СИ БИ България ЕООД 
Teл.: + 359 (0) 2 962 30 49 

Luxembourg/Luxemburg 
UCB Pharma S.A./NV 
Tél/Tel: + 32 / (0)2 559 92 00 
 

Česká republika 
UCB s.r.o. 
Tel: + 420 221 773 411 

Magyarország 
UCB Magyarország Kft. 
Tel.: + 36-(1) 391 0060 
 



185 

Danmark 
UCB Nordic A/S 
Tlf: + 45 / 32 46 24 00 

Malta 
Pharmasud Ltd. 
Tel: + 356 / 21 37 64 36 
 

Deutschland 
UCB Pharma GmbH 
Tel: + 49 /(0) 2173 48 4848 

Nederland 
UCB Pharma B.V. 
Tel.: + 31 / (0)76-573 11 40 
 

Eesti 
UCB Pharma Oy Finland 
Tel: + 358 9 25144221 

Norge 
UCB Nordic A/S 
Tlf: + 45 / 32 46 24 00 
 

Ελλάδα 
UCB Α.Ε.  
Τηλ: + 30 / 2109974000 

Österreich 
UCB Pharma GmbH 
Tel: + 43-(0)1 291 80 00 
 

España 
UCB Pharma S.A. 
Tel: + 34 / 91 570 34 44 

Polska 
UCB Pharma Sp. z o.o. 
Tel.: + 48 22 696 99 20 
 

France 
UCB Pharma S.A. 
Tél: + 33 / (0)1 47 29 44 35 

Portugal 
UCB Pharma (Produtos Farmacêuticos), Lda 
Tel: + 351 / 21 302 5300 
 

Hrvatska 
Medis Adria d.o.o. 
Tel: +385 (0) 1 230 34 46 
 

România 
UCB Pharma Romania S.R.L. 
Tel: + 40 21 300 29 04 
 

Ireland 
UCB (Pharma) Ireland Ltd. 
Tel: + 353 / (0)1-46 37 395 

Slovenija 
Medis, d.o.o. 
Tel: + 386 1 589 69 00 
 

Ísland 
Vistor hf. 
Tel: + 354 535 7000 

Slovenská republika 
UCB s.r.o., organizačná zložka 
Tel: + 421 (0) 2 5920 2020 
 

Italia 
UCB Pharma S.p.A. 
Tel: + 39 / 02 300 791 

Suomi/Finland 
UCB Pharma Oy Finland 
Puh/Tel: + 358 9 25144221 
 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Τηλ: + 357 22 34 74 40 
 

Sverige 
UCB Nordic A/S 
Tel: + 46 / (0) 40 29 49 00 
 

Latvija 
UCB Pharma Oy Finland 
Tel: + 358 9 25144221 
 

United Kingdom 
UCB Pharma Ltd. 
Tel : + 44 / (0)1753 534 655 
 

 
 
This leaflet was last revised in {MM/YYYY}  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu  



186 

INSTRUCTIONS FOR USE FOR THE CIMZIA INJECTION BY MEANS OF A DOSE-
DISPENSER CARTRIDGE  
 
Important information 
Read the instructions below carefully – this explains how to inject Cimzia by means of a dose-
dispenser cartridge. The dose-dispenser cartridge is also referred to as “medication”. 
 The medication is to be used with the electromechanical injection device called “ava” which is 

provided separately. 
 You must also carefully read the full instructions in the ava User Manual. 
You can inject yourself or the injection can be given by someone else (caregiver).  
If your doctor says you can inject yourself, you need to be fully trained first.  
 You will be instructed by your doctor or healthcare giver how to inject the medicine.  
 If something is not clear – please ask your doctor or pharmacist.  
 
Medication: dose-dispenser cartridge 

 
 

1. End cap 
2. Medication level indicator 
3. Syringe 
4. Medication information chip 
5. Needle cap 
6. Needle (inside cap) 
7. Medication body 
 
 
 

 
 
 
 
 
 
 
 
 
 



187 

Injection device: ava 
 

 

1. On/Off Button  

2. Start/Pause button  
3. Cartridge/Injection port  
4. Skin sensor (the skin sensor detects when the injection port is fully in contact with your skin).  
5. Scroll wheel (to adjust the speed of injection) 
6. Information screen  
7. Micro-USB Port  
 
1. Setting up 
 Remove the Cimzia carton from the refrigerator. 

– If the seal(s) is missing or broken – do not use and contact your pharmacist. 
• Remove the following items from the Cimzia pack and set them up on a clean flat surface: 

– One or two medication cartridge(s), depending on your prescribed dose 
– One or two alcohol wipe(s) 

 Look at the expiry date on the medication and pack. Do not use Cimzia after the expiry date 
which is stated on the pack and medication after EXP. The expiry date refers to the last day of 
the month shown. 

 Allow the medication to reach room temperature. This will take from 30 to 45 minutes. This 
will help reduce discomfort when injecting.  
– Do not heat the medication - let it warm up on its own. 
– Use a clean dry cloth to wipe off any condensation on the outside of the cartridge. 

 Do not remove the needle cap until ava instructs you to do so. 
 Wash your hands thoroughly. 
 
 



188 

2. Choosing and preparing an injection site 
• Choose a site on your thighs or tummy. 

 

 
• Each new injection should be given on a site separate from the last injection site. 

–  Do not inject in an area where the skin is reddened, bruised, or hard.  
– Wipe the injection site with an alcohol wipe, using a circular motion moving from the 

inside  
out. 
– Do not touch the area again before injecting.  

 
3. Injection 
• If you feel unsure about the injection process, contact your doctor or pharmacist.  
• Do not shake the medication. 
• Do not use the medication if it has been dropped after taking it out of the pack. 
• Turn on ava: 

– Press the  (On/Off button) for 1 second, or until the screen lights up and you hear 
sound 

– “Hello” is displayed for 2 seconds - this means ava is switched on.  
 ava then shows: 

– Your current dose and how often you need to inject it, 
– This is then followed by the message, “Inspect and then insert medication”. 

Check the medicine through the medication body.  
– Do not use if the solution is discoloured, cloudy or there are particles in it. 
– You may see air bubbles - this is normal. Injecting a solution subcutaneously which 

contains air bubbles is harmless. 

Check that the red “medication level indicator” is at the top of the cartridge.  
– The medication contains 1ml of Cimzia and is not completely full - this is normal. 
– Do not remove the needle cap from the medication yet.  



189 

 
 Firmly push the flat end cap into the medication/injection port at the bottom of ava – push until 

you hear a click.  
– Do not twist the dose-dispenser cartridge - it is a special shape so that it fits correctly. 

 
 Let go of the needle cap – this allows ava to check if the medication is usable. Do not remove 

the needle cap. 
– “Medication accepted” is shown if it is correct. 
– After a short pause, ava will automatically pull the cartridge in further. 

 The current injection speed (medication flow rate) is shown.  
– You can change this speed using the “scroll wheel” on the side of your ava. 
– You can choose “slowest”, “slow”, “fast” or “fastest” - this controls how fast the 

medicine will be injected and should be selected (and adjusted) as per your personal 
comfort preference. Your doctor can provide advice. 

 “Remove and save needle cap” is shown.  



190 

– Only remove the needle cap when you are ready to inject.  
 When ready, remove the needle cap by pulling it firmly downwards. 

– Once the needle cap has been removed, you must give the injection within 5 minutes. 
There is no need to rush your injection - 5 minutes gives you enough time. The time left 
is shown on screen. 

– Keep the needle cap - you will need it to remove the used medication from ava later. 

 
 Find a comfortable position and sit down for your injection.  

– Try to relax as this will make the injection more comfortable. 
 Place the orange skin sensor against the injection site where you are going to inject.  

– Position ava at a right angle on your skin with the screen facing you. This will make sure 
you are giving the injection correctly. 

– Position ava as shown so that you can comfortably reach the  (Start/Pause button) 
without moving ava.  

 
 Once ava is placed firmly against your skin “When ready press > once” is shown. 

 Press the (Start/Pause button).  
– As the injection is being given, keep holding ava firmly against your skin. 

– Avoid removing ava from the skin during the injection to ensure that you receive the full 
dose. 

– If ava is accidentally removed from your skin during the injection, the injection will 
automatically stop and the needle will go back into ava. To complete your injection: 
o Repeat Step 2 (Choosing and preparing an injection site), using a different injection 

site  
o Press ava firmly against the skin to begin the injection again, then  



191 

o Press the  (Start/Pause button). 
 If you feel unsure about the injection process, please contact your doctor or pharmacist. Do not 

try to repeat the injection process without speaking to your doctor or your pharmacist. 
 When the injection is complete, a message is shown on ava's screen saying "Injection complete. 

Please remove from skin" - you can then remove ava from you skin. 

 
 Use a piece of gauze, apply pressure over the injection site for a few seconds: 

– Do not rub the injection site. 
– You may cover the injection site with a small adhesive bandage, if necessary. 

 The messages “Needle uncapped! Handle with care!” and “Please replace needle cap” are 
shown until the needle cap is put back on. 

 Replace the needle cap. 
 Let go of the needle cap so that ava can push out the used medication. 
 When “Remove and discard used medication” is shown, pull out the medication using the 

needle cap. 
 Check the red medication level indicator is at the bottom of the cartridge - this shows you have 

had all of your injection. If the indicator is not at the bottom, contact your pharmacist. 

 
 
 
4. After Use 
 Do not re-use the cartridge 
• After injection, immediately throw away the used cartridge(s) in a special container as instructed 

by your doctor, nurse or pharmacist. 
• Keep the container out of the sight and reach of children. 
• If you need to have a second injection as prescribed by your doctor: 

– The message “You have 1 injection left” will be shown on screen. 



192 

– Repeat the injection process starting at Step 2. 

 
 Store ava in the storage case after use. 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS 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