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

Avacopan has shown efficacy as a glucocorticoid-sparing therapy in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but its benefit in patients with severe renal involvement treated with rituximab remains uncertain.

We conducted a retrospective comparative cohort study at Mayo Clinic including patients with AAV and estimated glomerular filtration rate (eGFR) < 30 ml/min per 1.73 m² at induction treated with rituximab plus avacopan (n = 30) or rituximab alone (n = 120) between 2010 and 2025. Coprimary outcomes were time to renal remission (no > 25% eGFR decline and hematuria ≤ 10 red blood cells per high-power field [RBC/HPF]), analyzed by Kaplan-Meier and Cox proportional hazards regression, and longitudinal eGFR trajectory, analyzed by linear mixed-effects models.

Baseline characteristics were well balanced. Median eGFR was 15.0 and 16.0 mL/min/1.73 m² 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 (hazard ratio [HR], 0.74, 95% confidence interval [CI], 0.45-1.21; P = 0.232). Longitudinal eGFR trajectories did not differ significantly between groups. One patient (3.3%) discontinued avacopan because of drug-induced liver injury, with transaminase normalization after discontinuation.

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.