THIS MANUSCRIPT IS PROVIDED IN CONFIDENCE TO DETERMINE REPRINT INTEREST ONLY AND SHOULD NOT BE DISTRIBUTED EITHER INTERNALLY OR EXTERNALLY VIA PRINT OR ELECTRONIC MEDIA FOR OTHER THAN THE STATED PURPOSE. The Long-Term Safety of Adalimumab Treatment in Moderate to Severe Psoriasis A Comprehensive Analysis of All Adalimumab Exposure in All Clinical Trials

Background: A favorable benefit-risk profile has been established for adalimumab, with up to 5 years of treatment in 13 clinical trials in patients with moderate to severe chronic plaque psoriasis. Objective: The aim of this analysis was to assess the long-term safety of all adalimumab exposure in all psoriasis clinical trials. Methods: A total of six sets of data were analyzed as follows: (i) all cumulative safety data from all exposure for all adalimumab-treated patients in the 13 clinical trials in moderate to severe psoriasis (All Adalimumab Treatment Population) through April 2007, November 2008, and November 2009, respectively; (ii) longitudinal data for 1403 patients treated with adalimumab 40 mg every other week (eow) dosing (Every Other Week Population) through June 2007 and April 2010; and (iii) data from placebo-controlled periods of clinical trials. Adverse events that occurred up to 70 days after the final dose of adalimumab were analyzed. Results: During placebo-controlled periods, a total of 572 patients had 173.0 patient-years (PYs) of exposure to placebo and 1188 patients had 370.5 PYs of exposure to adalimumab. Adverse event incidence rates, expressed as events per 100 PYs (events/100 PYs), for placebo- and adalimumab-treated patients for serious adverse events were 7.52 and 8.64, and for serious infectious adverse events were 2.89 and 2.43, respectively. In the 2007, 2008, and 2009 All Adalimumab Treatment Population there were, respectively, 1819 patients (2424.7 PYs), 2197 patients (4351.9 PYs), and 3010 patients (4844.7 PYs), with serious adverse event incidence rates of 6.51, 7.22, and 8.36 events/100 PYs, and serious infectious adverse event rates of 1.32, 1.38, and 1.65 events/100 PYs. In the 2007 and 2010 Every Other Week Population (n = 1403), there were 1883.5 and 2854.1 total PYs of exposure, respectively, with serious adverse event incidence rates of 6.32 and 6.87 events/100 PYs, and serious infectious adverse event rates of 1.33 and 1.37 events/100 PYs, respectively. Conclusions: Multiple lines of evidence from a total of six sets of safety data, with treatment for up to 5 years, including results from all adalimumab-treated patients, and a subset of patients treated with 40 mg eow dosing, did not show evidence of cumulative toxicity, and showed adverse event rates that were generally stable or decreased with increased mean per-patient exposure.