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Avacopan Mechanism ADVOCATE — SCE Rheumatology MCQ

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HardVasculitisAvacopan Mechanism ADVOCATESCE Rheumatology

A 55-year-old man with ANCA vasculitis is being considered for Avacopan as part of his induction regimen. What is the mechanism of action of Avacopan and what trial supported its approval?

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Correct answer: C — Avacopan is a selective complement C5a receptor antagonist that provides steroid-sparing induction treatment; the ADVOCATE trial demonstrated non-inferiority to standard glucocorticoid tapering when combined with Rituximab or Cyclophosphamide

Avacopan is an oral selective complement C5a receptor (C5aR) antagonist. C5a is a potent chemoattractant for neutrophils and a key mediator of vascular inflammation in ANCA vasculitis. The ADVOCATE trial (Jayne D et al 2021 NEJM) demonstrated that Avacopan was non-inferior to standard glucocorticoid taper and superior for sustained remission at 52 weeks when added to Rituximab or Cyclophosphamide induction. The key advantage is significant reduction in glucocorticoid exposure. NICE TA880 has approved Avacopan for ANCA vasculitis. It represents a major advance in steroid-sparing induction for AAV.

Reference: BSR 2025 AAV guidelines; Jayne D et al 2021 ADVOCATE trial NEJM; NICE TA880