Cotrimoxazole for infection prevention in glomerulonephritis treated with rituximab: a randomized controlled trial.

OBJECTIVES: We aimed to evaluate the safety and efficacy of cotrimoxazole for preventing infections in patients with glomerulonephritis (GN) receiving rituximab (RTX) therapy. STUDY DESIGN AND METHODS: This single-center, open-label randomized controlled trial enrolled 150 patients with GN who received RTX at Xijing Hospital between October 2022 and December 2023. Participants were randomized 1:1 to either the cotrimoxazole prophylaxis group (n = 75) or the non-cotrimoxazole group (n = 75). The primary endpoint was the cumulative incidence of infection over a 180-day follow-up period. Secondary endpoints included the incidence of severe infections and the rate of adverse events (AEs) attributed to cotrimoxazole. INTERVENTION: All patients received RTX at a dose of 1000 mg intravenously on days 1 and 14. CD19 + B-cell counts were monitored monthly for 6-month post-initial infusion; if CD19 + B cells remained detectable at the 6-month mark, an additional 1000-mg RTX dose was administered. COTRIMOXAZOLE PROPHYLAXIS PROTOCOL: Patients in the intervention group initiated oral cotrimoxazole on the same day as their first RTX infusion, with one tablet daily for seven consecutive days. Prophylaxis was repeated for 7 days following each subsequent RTX infusion, resulting in a total of 14 days of prophylaxis over the study period. THE NON-COTRIMOXAZOLE GROUP: They received no cotrimoxazole prophylaxis. RESULTS: Over 180 days of follow-up, 8 infectious episodes occurred in 7 patients in the cotrimoxazole group, compared with 19 episodes in 16 patients in the control group. The annualized incidence density of infections (per 100 person-years) was 20.80 (95% CI 11.36-30.24) in the cotrimoxazole group versus 54.83 (95% CI 43.09-66.57) in the control group. The hazard ratio (HR) for the cumulative incidence of infection was 0.39 (95% CI 0.17-0.88; log-rank test, P = 0.029), indicating a significant reduction in infection risk with cotrimoxazole prophylaxis. CONCLUSIONS: Our findings demonstrate that cotrimoxazole prophylaxis for 1-week post-RTX infusion effectively prevents post-RTX infectious complications, reduces infection-related mortality, and does not elevate the risk of serious AEs. However, it should be noted that this study was a single-center investigation without a placebo control. TRIAL REGISTRATION: The study was registered on the Chinese Clinical Trial Registry (trial registration identifier: ChiCTR2200063564).