Rituximab for Relapsing Nephrotic Syndrome in Adults: A Randomized Clinical Trial

Importance: The effects of rituximab on relapse of nephrotic syndrome in patients with adult-onset frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS) remain uncertain. Objective: To evaluate the effects of rituximab for patients with FRNS or SDNS. Design, Setting, and Participants: Multicenter, double-blind, randomized, placebo-controlled trial conducted at 13 centers in Japan. Adults with FRNS or SDNS who had urine protein of less than 0.3 g/gCr were enrolled between September 1, 2020, and June 28, 2022. Final follow-up occurred on March 15, 2024. Interventions: Patients were randomized to receive either intravenous rituximab, 375 mg/m² (n = 36), or placebo (n = 36) at weeks 1, 2, and 25. Patients were followed up for 49 weeks. Main Outcomes and Measures: The primary outcome was the proportion of patients who were free of relapse of nephrotic syndrome at 49-week follow-up. Relapse was defined as urine protein of at least 1 g/gCr on 2 consecutive measurements. Results: Among 72 randomized participants (mean age, 47.9 years; 56.1% female), 66 (92%) received the study drug at least once and were included in analyses. The relapse-free rate at week 49 was 87.4% (95% CI, 69.8%-95.1%) in the rituximab group and 38.0% (95% CI, 22.1%-53.8%) in the placebo group (P <.001 by 1-sided log-rank test). One of 18 secondary outcomes was statistically significant (favoring rituximab). The median relapse-free time in the rituximab group was greater than 49.0 weeks and in the placebo group was 30.8 weeks. A stratified Cox model showed a hazard ratio for relapse of 0.16 (95% CI, 0.05-0.46; P <.001) in the rituximab group compared with the placebo group. The most common adverse effect was infusion reaction (13 [40.6%] in the rituximab group and 1 [2.9%] in the placebo group). Conclusions and Relevance: These results support use of rituximab to prevent relapse in adults with FRNS or SDNS.