Real-world efficacy and safety of avacopan in ANCA-associated vasculitis: a retrospective comparative study

Avacopan, an oral C5a receptor antagonist, is approved for treatment of severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in combination with rituximab or cyclophosphamide. This study evaluated its real-world efficacy, safety and glucocorticoid-sparing effects.

This retrospective single-centre study included 35 patients with new-onset or relapsing AAV treated with avacopan plus standard induction therapy (rituximab, cyclophosphamide or both). Outcomes were compared with 70 matched controls receiving standard therapy. Primary endpoints were remission (Birmingham Vasculitis Activity Score (BVAS)=0, prednisolone ≤5 mg/day) at 6 and 12 months. Secondary endpoints included relapse, renal function, glucocorticoid exposure and adverse events.

Baseline characteristics were generally comparable, although median estimated glomerular filtration rate (eGFR) was lower in the avacopan group (24 vs 49 mL/min). Induction therapy included rituximab (28%), cyclophosphamide (11%) or combination therapy (61%), reflecting severe disease. Remission rates were similar at 6 months (69% vs 68%) but tended to be higher with avacopan at 12 months (86% vs 68%; p=0.11). Relapses occurred less frequently with avacopan (16% vs 51%, p=0.003), including after treatment discontinuation. Avacopan was associated with accelerated glucocorticoid tapering (≤5 mg/day; 102 vs 164 days, p<0.001), lower cumulative doses (3266 vs 4288 mg, p=0.008) and greater renal function improvement (ΔeGFR+18 vs +7 mL/min after 1 year). Nine patients (26%) discontinued avacopan due to adverse events.

In a real-world practice, avacopan was effective with an acceptable safety profile, enabling steroid sparing, improved renal recovery and reduced relapse rates, including in patients receiving combined induction therapy. Benefits persisted beyond 12 months, but prospective confirmation of these presumed long-term benefits is needed.