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

We aimed to evaluate the safety and efficacy of cotrimoxazole for preventing infections in patients with glomerulonephritis (GN) receiving rituximab (RTX) therapy.

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.

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.

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.

They received no cotrimoxazole prophylaxis.

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.

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.

The study was registered on the Chinese Clinical Trial Registry (trial registration identifier: ChiCTR2200063564).