Cimzia Adverse Reactions

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-radiographic 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 Pharmacology: Pharmacodynamics under Actions). 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 post-marketing cases at least possibly related to Cimzia are listed in Table 13 as follows, 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. (See Table 13.)

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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 Contraindications and Precautions).
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 Precautions).
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 Precautions). 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 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.