Real-world avacopan use in ANCA-associated vasculitis: first experiences in Northern Ireland

Background Avacopan, an oral C5a-receptor inhibitor, demonstrated improved remission and renal outcomes in the pivotal randomised ADVOCATE trial in ANCA-associated vasculitis (AAV). However, evidence from routine clinical practice remains limited, particularly in the United Kingdom and among patients with advanced kidney disease. We assessed early real-world use of avacopan across Northern Ireland before subsequent regulatory action concerning the integrity and reliability of data from ADVOCATE. Methods In this retrospective multicentre cohort study, adults with newly diagnosed or relapsing AAV who received avacopan between March 2023 and July 2025 in the five Northern Ireland Health and Social Care Trusts were identified from electronic healthcare records (EHCR). Data on demographics, disease phenotype, kidney function, concomitant immunosuppression, glucocorticoid exposure, relapses, and adverse events and remission rates were collected. Results Forty patients started avacopan; median age was 61 years, 75% had newly diagnosed disease, and 77.5% had renal involvement, including 30% with eGFR < 15 mL/min/1.73 m² and 15% on kidney replacement therapy. Remission was achieved in 65.6% (21/32) at week 26 and sustained in 60.0% (15/25) at week 52. Mean eGFR increased by 9.6 and 10.4 mL/min/1.73 m² at weeks 26 and 52 respectively, with the largest gains in patients with baseline eGFR < 30 and < 15 mL/min/1.73 m²; among six patients dialysis-dependent at presentation, five discontinued kidney replacement therapy and remained dialysis-free at last follow-up. Early initiation (≤ 30 days) was associated with numerically greater renal recovery but similar steroid withdrawal. Overall, 75% discontinued glucocorticoids, usually within 8 weeks. Adverse events occurred in 67.5% of patients, with serious infections in 10% and transaminitis in 15%. Avacopan was permanently discontinued in 25%. Conclusions In routine practice across Northern Ireland, avacopan used alongside contemporary immunosuppression was associated with high remission rates and improved kidney function, including recovery of dialysis independence in a small subgroup who presented with kidney failure, although this observation cannot be causally attributed to avacopan in the absence of a comparator. These findings describe early real-world outcomes of avacopan use in severe AAV and provide post-marketing evidence to inform its effectiveness and safety in clinical practice, particularly in the context of uncertainty surrounding the pivotal controlled-trial evidence. Clinical trial number Not applicable.