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.