Efficacy of Avacopan in ANCA associated vasculitis: A meta-analysis of randomized controlled trials

Background Avacopan is a novel C5a inhibitor that has shown promise in treating ANCA-associated vasculitis. We aimed to compare its therapeutic effects and efficacy with the current standard of care, which typically includes high-dose steroids and other immunosuppressive agents, such as cyclophosphamide, rituximab, and azathioprine. Methods We conducted a meta-analysis of randomized controlled trials that compared the therapeutic effects of avacopan with those of the standard of care. We selected three trials from five databases, including Cochrane, PubMed, Science Direct, Google Scholar, and ClinicalTrials.gov as of February 15, 2025. The primary outcomes were change in GFR, percent change in Urine Albumin Creatinine Ratio (UACR), and proportion of subjects achieving disease remission. The secondary outcome was the percent change in the Monocyte Chemoattractant Protein(MCP1)/creatinine ratio. The results are presented as mean differences for continuous variables or odds ratios for dichotomous variables. Results Three trials including 404 patients (204 avacopan, 200 standard care) were analyzed. Avacopan was associated with a significantly smaller reduction in proteinuria (mean difference in UACR change: 7; 95% CI: 5.75–8.25; p<0.00001) and a greater reduction in MCP-1/creatinine ratio (mean difference: -3; 95% CI: -3.81 to -2.19; p<0.00001). Differences in GFR change and remission rates were not statistically significant. Conclusion In conclusion, avacopan has beneficial steroid-sparing effects, but it may not be a viable alternative on its own. Further long-term studies are needed to better evaluate the efficacy and the risk of adverse effects associated with the use of avacopan in conjunction with low-dose steroid use.