Integrated safety profile of atacicept: an analysis of pooled data from the atacicept clinical trial programme

摘要

Objective To characterize the overall safety profile of atacicept, we conducted an integrated analysis of pooled safety data from all 17 clinical studies to date. Methods Three data sets were used to investigate safety endpoints: a double-blind placebo-controlled set ( n?= 1568), an SLE set ( n?= 761) and a full analysis set ( n?= 1845; including all 17 studies). Results Of 1568 patients in the double-blind placebo-controlled-set, 30.8% received placebo, and 8.2, 24.5 and 36.5% received atacicept 25, 75 and 150?mg, respectively. Treatment-emergent adverse event (TEAE) rates (adjusted by treatment-exposure) were generally higher with atacicept vs placebo, but no consistent association was found between atacicept dose and specific TEAEs or mortality. Serious infection and serious TEAE rates were similar for atacicept and placebo. The TEAE-related discontinuation rates were higher with atacicept vs placebo (16.1 vs 10.9/100 patient-years). In the full analysis set, 11 deaths occurred during treatment. Across indications, exposure-adjusted mortality rates/100 patient-years (95% CI) were 3.60 (0.90, 14.38), 0.34 (0.05, 2.43) and 1.18 (0.49, 2.82) with atacicept 25, 75 and 150?mg, respectively, and 0.44 (0.06, 3.12) with placebo. In SLE patients, exposure-adjusted mortality rates were 1.45 (0.54, 3.87) with atacicept 150?mg and 0.78 (0.29, 2.07) across all atacicept-treated patients. No deaths occurred with atacicept 75?mg or placebo. In the SLE and double-blind placebo-controlled sets, pharmacodynamic effects of atacicept were not associated with increased infection rates. Conclusion The results of this integrated safety analysis support further development and evaluation of atacicept in selected patients for whom potential benefits might outweigh risks. atacicept , autoimmune diseases , safety , B-cell targeting , clinical trials , systemic lupus erythematosus , adverse events Key message Integrated analysis of atacicept clinical studies supports further evaluation in selected patients if benefits outweigh risks.