Real-world effectiveness of rituximab or intravenous cyclophosphamide versus non-use in patients with severe microscopic polyangiitis and granulomatosis with polyangiitis: a retrospective cohort study of J-CANVAS.

Objectives: To evaluate the real-world effectiveness of rituximab (RTX) and intravenous cyclophosphamide (IVCY) compared to non-use for remission induction in microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA).

Methods: This observational study emulated a target trial using data from the Japan Collaborative Registry of ANCA-Associated Vasculitis (J-CANVAS). Patients aged ≥20 years with newly diagnosed or relapsing MPA or GPA (2017-2023) were included. RTX or IVCY use within 4 weeks defined the treatment group; others formed the control group. The primary outcome was failure to achieve remission at week 24 (BVAS = 0 and prednisolone ≤ 10 mg/day). Secondary outcomes included a composite of death, kidney failure, and relapse, and serious infection. In inverse probability weighted population, risk ratios were estimated using modified Poisson regression.

Results: Among 544 patients (MPA: 413, GPA: 131), 63.6% received RTX or IVCY. The risk ratio for failure to achieve remission was 0.72 (95% CI: 0.61-0.85), and for the composite outcome was 0.57 (95% CI: 0.33-0.97), and for serious infection was 1.03 (95% CI, 0.47-2.25). Results were robust in sensitivity analyses.

Conclusions: RTX and IVCY improved short-term outcomes in MPA and GPA without increasing infection risk, supporting their recommendation as standard therapy.