Making use of avacopan in clinical practice
Chan, Chi Peng Hussain, Azm Ul Chanouzas, Dimitrios Harper, Lorraine
Chan, Chi Peng
Hussain, Azm Ul
Chanouzas, Dimitrios
Harper, Lorraine
Affiliation
Other Contributors
Publication date
2025-12-09
Subject
Collections
Research Projects
Organizational Units
Journal Issue
Abstract
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a severe multisystem autoimmune disease in which renal involvement is common and often progresses, without timely intervention, to end-stage kidney disease. Standard remission induction therapy combines high-dose glucocorticoids (GCs) with cyclophosphamide or rituximab. While effective, cumulative GC exposure drives substantial treatment-related morbidity, including infection, diabetes, osteoporosis and cardiovascular complications, highlighting the urgent need for GC-sparing strategies. Avacopan, an oral selective C5a receptor antagonist, represents a novel therapeutic approach targeting the alternative complement pathway, a key mediator of neutrophil activation and vascular injury in AAV. The pivotal phase 3 ADVOCATE trial demonstrated that avacopan achieved non-inferior remission at 26 weeks and superior sustained remission at 52 weeks compared with a standard GC taper, while reducing GC-related toxicity and improving renal recovery, particularly in patients with advanced kidney impairment. Since approval in 2021, real-world studies and case series have given further confidence in avacopan's efficacy across diverse patient subgroups, including those with severe renal disease, diffuse alveolar haemorrhage and refractory manifestations. However, real-world data also highlight variability in GC tapering practices and safety signals, particularly hepatotoxicity in Japanese cohorts. Several unanswered questions remain, including the long-term safety, clinical benefit of treatment beyond 1 year and optimal GC concomitant use or even the feasibility of complete GC avoidance. Ongoing large-scale studies and international real-world evidence will be essential to define avacopan's optimal role in clinical practice, ensuring equitable access for patients with AAV.
Citation
Chan CP, Hussain AU, Chanouzas D, Harper L. Making use of avacopan in clinical practice. Clin Kidney J. 2025 Dec 9;19(1):sfaf388. doi: 10.1093/ckj/sfaf388.
Type
Article