An analysis of the long-term safety of certolizumab pegol (Cimzia, UCB [CZP]) treatment in adults with rheumatoid arthritis (RA) was recently conducted by Bykerk et al.1 They evaluated data through Nov. 30, 2011, from 10 completed randomized controlled trials (RCT), one open-label, single-dose pharmacokinetic study and seven open-label extension trials.
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Some of these patients have been receiving CZP for up to seven years. All adverse events that occurred from the first day to 84 days after the last dosing day were noted. Any serious infections, malignancies and deaths were evaluated by external experts and validated by an external committee. Event rates (ERs) and incidence rates (IRs) per 100 patient-years (PYs) were reported. Patients had received either 200 mg CZP every two weeks following a loading dose of 400 mg; CZP 400 mg once every four weeks; or 400 mg every two weeks. The drug was administered as either the reconstituted lyophilized powder for injection or in a prefilled syringe for subcutaneous injection. Overall, 4,049 RA patients who received CZP were included in the safety pooling, with a total exposure of 9,277 PYs, and a mean exposure of 2.1 years (range, 0.04–7.6 years).
The most common serious adverse event was pneumonia, occurring more frequently in CZP-treated (vs. placebo-treated) patients. Serious infectious events were lower in CZP-treated patients.
Tuberculosis (TB) was identified in 44 patients, of whom 39 were from high endemic regions. TB screening was conducted following respective national guidelines of the study center before 2007. Subsequently, any patient with a positive purified protein derivative test received prophylaxis.
Other opportunistic infections were bronchopulmonary aspergillosis (n=6), esophageal or oral candidiasis (n=9) and disseminated herpes zoster (n=3). In addition, 70 malignancies, including five lymphomas, were identified. Non-melanoma skin cancers were excluded. Infections were the most common reason for study withdrawal.
For patients in the open-label extensions, the rate of serious infections did not increase with prolonged exposure to CZP, which is in line with that reported in the literature for other TNF inhibitors.
In the RCT, there were 11 deaths in CZP-treated patients and one death of a placebo-treated patient.
Across all trials, there were 58 CZP-treated patient deaths, mostly related to cardiovascular events, malignancies and infections. There were no cases of optic neuritis, multiple sclerosis or other demyelinating disorders identified. The overall adverse event incidence rate was 335.9 per 100 PYs for CZP-treated patients vs. 362.3 per 100 PYs for placebo-treated patients. Most adverse events were mild to moderate in intensity. The authors noted that for patients in the open-label extensions, the rate of serious infections did not increase with prolonged exposure to CZP, which is in line with that reported in the literature for other TNF inhibitors. In other words, no new or unexpected safety signals.