Abstract
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: double-blind placebo-controlled (DBPC) set (n = 1568), SLE set (n = 761) and full analysis (FA) set (n = 1845; including all 17 studies).
Results: Of 1568 patients in the DBPC-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. TEAE-related discontinuation rates were higher with atacicept vs placebo (16.1 vs 10.9/100 patient-years). In the FA set, 11 deaths occurred during treatment. Across
indications, exposure-adjusted mortality rates/100 patient-years (95% confidence interval) 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 DBPC 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 may outweigh risks.
Methods: Three data sets were used to investigate safety endpoints: double-blind placebo-controlled (DBPC) set (n = 1568), SLE set (n = 761) and full analysis (FA) set (n = 1845; including all 17 studies).
Results: Of 1568 patients in the DBPC-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. TEAE-related discontinuation rates were higher with atacicept vs placebo (16.1 vs 10.9/100 patient-years). In the FA set, 11 deaths occurred during treatment. Across
indications, exposure-adjusted mortality rates/100 patient-years (95% confidence interval) 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 DBPC 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 may outweigh risks.
| Original language | English |
|---|---|
| Article number | rkz021 |
| Number of pages | 12 |
| Journal | Rheumatology Advances in Practice |
| Volume | 3 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 6 Aug 2019 |
Keywords
- B cell targeting
- adverse events
- atacicept
- autoimmune diseases
- clinical trials
- safety
- systemic lupus erythematosus