Efficacy and safety of avacopan in the treatment of ANCA-associated vasculitis: a systematic review and meta-analysis.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a dangerous autoimmune condition that usually requires high-dose glucocorticoids with immunosuppressive agents. Although effective, long-term glucocorticoid use is associated with significant toxicity. Avacopan, a selective inhibitor of C5a receptors, has emerged as a possible glucocorticoid-sparing drug for AAV, potentially offering a safer, more specific approach to treat the disease. This systematic review and meta-analysis aimed to compare the efficacy and safety of avacopan and conventional glucocorticoid-containing regimens for the treatment of AAV. METHODS: A systematic search was conducted in PubMed, Embase, Scopus, and the Cochrane Library between 2000 and 2025. Post hoc subgroup analyses, randomized controlled trials, and observational reports that compared avacopan with glucocorticoid regimens in GPA or MPA patients were included. The primary outcomes were remission at week 26 and sustained remission at week 52. The secondary outcomes were relapse rates, renal outcomes, adverse events, glucocorticoid toxicity, and health-related quality of life. RESULTS: Nine studies with 2080 patients were combined. Compared with glucocorticoids, avacopan was associated with noninferior remission rates at week 26 and significantly higher sustained remission rates at week 52 (RR = 1.02, 95% CI: 0.88–1.19). It was associated with significantly reduced glucocorticoid toxicity, fewer adverse events, and improved quality of life scores. Heterogeneity was low (I2 = 5.4%), which supported the consistency of the results. CONCLUSIONS: Compared with standard glucocorticoid treatment, avacopan appears to offer a safer alternative with similar disease control and significantly reduced toxicity. These findings suggest a potential shift towards less toxic and more personalized approaches in AAV management, though further research is warranted to confirm these benefits. TRIAL REGISTRATION: PROSPERO CRD420251033866. CLINICAL TRIAL NUMBER: Not applicable.