Real world use of avacopan for ANCA-associated vasculitis. First experiences in Ireland.

Background Avacopan, a selective complement 5a receptor (C5aR) antagonist, is used for the treatment of severe active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in combination with rituximab or cyclophosphamide. By reducing glucocorticoid exposure and associated toxicity, avacopan can improve patient outcomes. This report presents the first clinical experience with avacopan in the treatment of ANCA-associated vasculitis (AAV) in the Republic of Ireland. Methods Ten patients received avacopan between December 2017 and April 2024 through the Irish early access program and the ADVOCATE trial (n=2). Data were extracted from the RITA Ireland Vasculitis (RIV) database and retrospective chart review. Collected variables included the commencement date, indication for avacopan initiation, ANCA subtype, organ involvement, number of relapses, concurrent and prior immunosuppressive medications, and adverse events. Results Avacopan was primarily initiated for patients requiring a steroid-sparing regimen due to contraindications such as severe osteoporosis, prior eating disorders, anxiety, or steroid-induced psychosis, as well as patient preference to avoid corticosteroids. On average, patients received 2.285 grams of prednisolone equivalent prior to avacopan initiation (range: 0–8.125 grams). Most patients achieved disease control without requiring further steroid therapy. Avacopan is generally well-tolerated. The reported adverse events in this cohort were headache, limited maculopapular rash, neutropenia, and liver dysfunction. Two patients experienced disease relapse upon discontinuation of avacopan, both of whom had the longest follow-up durations. Conclusion This study is the first real-world evaluation of avacopan use in Ireland. Although the sample size was small, avacopan demonstrated a favourable safety profile and efficacy in reducing corticosteroid dependence. As of July 1, 2024, avacopan was funded by the Irish Health Service Executive, improving accessibility. Further long-term follow-up is warranted to assess the relapse risk and establish the optimal treatment duration.