The Complement System in ANCA‐Associated Vasculitis: Mechanistic Insights, Therapeutic Horizons, and Unmet Clinical Needs

Complement dysregulation is a pivotal mechanism in AAV pathogenesis, opening a new era of complement-targeted therapies. Avacopan's success illustrates the potential to improve outcomes and safety by modulating complement. Yet, major unmet clinical needs remain. Up to 50% of patients relapse within 5 years. There are no validated biomarkers to predict relapse. Long-term steroid dependence and cumulative toxicity from rituximab and cyclophosphamide compromise patient safety. Better tools are needed to detect early disease, stratify relapse risk, and personalize therapy. Future directions must prioritize biomarker development, novel complement inhibitors, and deliver durable remission with fewer side effects.