Efficacy and Safety of Avacopan in ANCA-Associated Vasculitis: A Meta-Analysis of Randomized Controlled Trials

BACKGROUND: Avacopan, an oral C5a receptor antagonist, has been identified as a promising glucocorticoid-sparing agent in the management of ANCA-associated vasculitis (AAV). Although individual randomized controlled trials (RCTs) have indicated its therapeutic potential, there remains a need for comprehensive integration of efficacy and safety data to guide clinical decision-making. METHODS: We performed a meta-analysis of three pivotal RCTs-CLASSIC (n = 42), CLEAR (n = 67), and ADVOCATE (n = 331)-including a total of 440 individuals diagnosed with AAV. Primary endpoints encompassed clinical response, sustained and early remission rates, changes in renal function, as well as safety outcomes such as serious adverse events, infections, organ toxicity, hematologic complications, and glucocorticoid-related adverse effects. Summary effect estimates were derived using risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI). Study heterogeneity was quantified using the I² statistic and corresponding p-values. RESULTS: Avacopan was associated with efficacy outcomes that were equivalent to or exceeded those achieved with standard-of-care regimens. Clinical response (RR = 1.08; 95% CI: 0.98-1.19) and early remission (RR = 2.85; 95% CI: 0.95-8.54) favored avacopan. Improvements in renal parameters, including eGFR and renal response, were consistent but modest. Notably, avacopan substantially decreased glucocorticoid-related adverse events (RR = 0.78; 95% CI: 0.70-0.87; p <0.0001), particularly the incidence of diabetes, psychiatric complications, and general GC toxicity. Avacopan did not result in any significant increase in serious infections, mortality, or treatment discontinuations. CONCLUSIONS: Avacopan represents a highly effective and safer option compared to traditional glucocorticoid-based regimens for AAV. The capacity to sustain disease remission with reduced steroid-associated harm highlights its potential utility in evolving vasculitis treatment strategies.