Adalimumab safety in global clinical trials of patients with Crohn's disease

Background: Adalimumab, a fully human anti‐tumor necrosis factor (anti‐TNF) monoclonal antibody, is approved for the treatment of Crohn's disease (CD) in adults. We evaluated the overall safety profile of adalimumab in global clinical trials in patients with CD. Patients who participated in these trials, which included randomized induction and maintenance trials, Phase IIIb trials, and open‐label extension studies, had moderately to severely active CD and were evaluated for safety at regular intervals. Methods: Rates of adverse events of interest were assessed per 100‐patient‐years of adalimumab exposure. Standardized mortality rates and standardized incidence rates (for malignancies) were calculated using population‐matched data. As of April 15, 2008, 3160 patients with CD had been treated with adalimumab in clinical trials, representing 3401.9 patient‐years of adalimumab exposure. Results: Serious infection was the most frequently reported serious adverse event of interest in the CD trials; abscess (intraabdominal and gastrointestinal related) was the most common serious infection. Low incidences of malignancies, lymphomas, opportunistic infections (including tuberculosis), demyelinating disorders, and lupus‐like disorders were reported in the CD trials. The standardized mortality rate for adalimumab‐treated patients with CD, 0.44 (95% confidence interval [CI], 0.12–1.12), is less than the rate of 1.52 (95% CI, 1.32–1.74) reported in a recent meta‐analysis of patients with CD. Conclusions: The safety profile of adalimumab in patients with CD was similar to that of other TNF antagonists in CD populations, and the rates of adverse events were comparable to other approved indications for adalimumab spanning >10 years of clinical observation. No new safety signals were identified. (Inflamm Bowel Dis 2009)