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Rituximab With or Without Avacopan in ANCA-Associated Vasculitis With Severe Renal Involvement

Year: 2026

Type: article

Abstract: Introduction Avacopan has demonstrated efficacy as a glucocorticoid-sparing therapy in ANCA-associated vasculitis (AAV), but its benefit in patients with severe renal involvement treated with rituximab remains uncertain. Methods We conducted a retrospective comparative cohort study at Mayo Clinic including patients with AAV and eGFR <30 mL/min/1.73 m 2 at induction treated with rituximab plus avacopan (n=30) or rituximab alone (n=120) between 2010 and 2025. Co-primary outcomes were time to renal remission (no >25% eGFR decline and hematuria ≤10 RBC/HPF), analyzed by Kaplan-Meier and Cox proportional hazards regression, and longitudinal eGFR trajectory, analyzed by linear mixed-effects models. Results Baseline characteristics were well balanced. Median eGFR was 15.0 and 16.0 mL/min/1.73 m 2 and dialysis was required at baseline in 13.3% and 12.5% in the avacopan and rituximab groups, respectively. Avacopan significantly reduced cumulative prednisone exposure at 12 months (1.8 vs 4.3 g; p<0.001) and shortened time to prednisone discontinuation (3.3 vs 7.3 months; log-rank p<0.001). On adjusted Cox regression, renal remission did not differ significantly between groups (HR 0.74, 95% CI 0.45–1.21; p=0.232). Longitudinal eGFR trajectories did not differ significantly between groups. One patient (3.3%) discontinued avacopan due to drug-induced liver injury, with transaminase normalization following discontinuation. Conclusion In our cohort of patients with AAV and severe renal involvement treated with rituximab-based induction, avacopan did not improve renal remission rates or longitudinal eGFR trajectory in comparison to glucocorticoids but achieved significant and faster glucocorticoid reduction with an acceptable safety profile.

Source: Kidney International Reports

DOI: 10.1016/j.ekir.2026.107009