Systematic Review of Efficacy and Safety of Avacopan in Real-World Clinical Practice.

Introduction: Avacopan, a complement 5a receptor (C5aR) antagonist, is a therapeutic option for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and is used as a steroid-sparing agent. The efficacy and safety of avacopan were established in the pivotal phase III ADVOCATE trial. However, there remains a paucity of real-world evidence to confirm these findings across diverse clinical settings and populations. Methods: We conducted a systematic review of 16 real-world studies evaluating the clinical outcomes of avacopan in patients with AAV. Using a meta-analytic approach, we compared efficacy and safety outcomes reported in these studies with those of the main trial. Key end points included clinical remission and incidence of adverse events. Results: The aggregated real-world data demonstrated that the time from diagnosis of AAV or relapse and initiation of avacopan was 24 days (range: 6-54 days). The clinical remission rates at 6 months as assessed in 215 patients were 89% (95% confidence interval [CI]: 0.84-0.93), whereas the rates of serious infection were 14% (95% CI: 0.10-0.18). We observed a heterogeneity between populations when hepatotoxicity was assessed in real-world cohorts, with this signal being particularly pronounced in Japanese populations. Conclusion: Avacopan has been found to demonstrate both safety and high efficacy in the treatment of AAV in real-world settings, with remission rates exceeding and serious infection rates comparable to those observed in clinical trial data. However, the higher incidence of hepatotoxicity in certain populations underscores the need for careful monitoring and pharmacovigilance studies to clarify risk factors and guide patient selection.