Long-term efficacy of rituximab versus intravenous cyclophosphamide for severe ANCA-associated vasculitis in multicenter REVEAL cohort study.

Background: The optimal remission induction therapy for severe antineutrophil cytoplasmic antibody-associated vasculitis (AAV) remains unclear. This study evaluated the effectiveness of rituximab (RTX) as a remission induction therapy for severe AAV compared with intravenous cyclophosphamide (IVCY).

Methods: Patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) treated with systemic glucocorticoids (GCs) and IVCY or RTX as initial remission induction therapy in multicenter REVEAL study between 1991 and 2024 were enrolled. We compared efficacy and safety outcomes between the two groups. Effectiveness was evaluated using all-cause mortality, GC-remission rate, relapse rate, and end-stage renal disease (ESRD) progression rate. Safety was evaluated based on complications from severe infections. Inverse probability of treatment weighting (IPTW) was applied for selection bias.

Results: Of 555 patients with AAV, 178 with severe MPA or GPA were identified (IVCY group: N = 133, RTX group: N = 45). After adjustment by IPTW, no significant differences in baseline clinical characteristics were observed between them. The 10-year survival rate and GC-remission rate at 6 months were significantly higher in the RTX group (p = 0.04, p = 0.017, respectively). ESRD progression and relapse rates were comparable between two groups. Regarding safety, 15.2% of patients in the IVCY group died due to severe infections, whereas none did in the RTX group (p = 0.007).

Conclusions: RTX demonstrated superior efficacy in improving survival and achieving GC remission, with fewer infection-related deaths compared to IVCY in patients with severe AAV. These findings reveal the efficacy and safety of RTX as a remission induction therapy in real-world Japanese clinical practice.