Safety of adalimumab in global clinical trials of patients with Crohn's disease.

Abstract

Purpose: Adalimumab (ADA), a fully human anti-TNF monoclonal antibody, is approved in Europe for treating patients with severely active Crohn's disease (CD) who have had an inadequate response to conventional therapy. Methods: All patients with CD participating in the pivotal randomized controlled clinical trials, open-label extensions, and Phase IIIb studies were evaluated for safety at regular intervals. Rates of adverse events (AEs) of interest to physicians prescribing anti-TNF therapy were assessed per 100-patient-years (100-PYs) of ADA exposure. Standardized mortality ratios were calculated using the World Health Organization 2003 age- and sex-matched US mortality data. Results: As of 6 November, 2009, the ADA CD clinical trial safety database contained data for 3603 patients (4088-PYs of ADA exposure). Table 1 compares AE rates observed in all clinical trials in CD at the 6 November 2009 cutoffto those from the 15 April 2008 safety update.1 Observed cases of lymphoma (2), tuberculosis (3), congestive heart failure (2), and demyelinating disease (6) have not increased since the previous update. The AE rates were comparable to those reported in rheumatoid arthritis trials.2 The calculated standardized mortality ratio in ADA-treated patients with CD, 0.48 (95% confidence interval [CI]: 0.15, 1.12), is lower than the rate of 1.52 (95% CI: 1.32, 1.74) reported in a recent meta-analysis of patients with CD.3 Conclusion: The safety profile and AE rates for ADA in CD were similar to those reported previously for ADA and other TNF antagonists in CD populations. 4,5 ADA was well-tolerated, and no new safety signals were identified. (Table Presented).