近日，日本群马大学医学院Keiju Hiromura团队研究了利妥昔单抗治疗成人复发性肾病综合征的随机临床试验。相关论文发表在2025年11月5日出版的《美国医学会杂志》上。

利妥昔单抗对成年性频繁复发肾病综合征（FRNS）或类固醇依赖性肾病综合征（SDNS）患者肾病综合征复发的影响尚不确定。

为了评估利妥昔单抗对FRNS或SDNS患者的疗效，研究组在日本的13个中心进行了一项多中心、双盲、随机、安慰剂对照试验。在2020年9月1日至2022年6月28日期间，尿蛋白低于0.3 g/gCr的FRNS或SDNS成人被纳入研究。最后一次随访发生在2024年3月15日。患者在第1、2和25周随机接受静脉注射利妥昔单抗，375 mg/m² (n=36)或安慰剂(n=36)。随访49周。主要结局是在49周的随访中没有肾病综合征复发的患者比例。复发定义为连续2次尿蛋白≥1g /gCr。

在72名随机受试者（平均年龄47.9岁，56.1%为女性）中，66名（92%）至少接受过一次研究药物，并被纳入分析。第49周时，利妥昔单抗组无复发率为87.4% (95% CI, 69.8% ~ 95.1%)，安慰剂组为38.0% (95% CI, 22.1% ~ 53.8%) （P <0.001，单侧log-rank检验)。18个次要结局中有一个具有统计学意义（利妥昔单抗有利）。利妥昔单抗组的中位无复发时间大于49.0周，安慰剂组的中位无复发时间为30.8周。分层Cox模型显示复发的风险比为0.16 （95% CI, 0.05-0.46; P <0.001)，利妥昔单抗组与安慰剂组比较。最常见的不良反应是输液反应（利妥昔单抗组13例[40.6%]，安慰剂组1例[2.9%]）。

研究结果表明，这些结果支持使用利妥昔单抗预防FRNS或SDNS成人复发。

附：英文原文

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

Author: Yoshitaka Isaka, Yusuke Sakaguchi, Maki Shinzawa, Shoichi Maruyama, Mika Sakaguchi, Hiroki Hayashi, Yusuke Kaida, Shin Goto, Tatsuo Tsukamoto, Akito Maeshima, Yoichiro Ikeda, Norihiko Sakai, Naoki Sawa, Kengo Furuichi, Kunihiro Yamagata, Takehiko Wada, Yugo Shibagaki, Keiju Hiromura

Issue&Volume: 2025-11-05

Abstract:

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.

DOI: 10.1001/jama.2025.19316

Source: https://jamanetwork.com/journals/jama/fullarticle/2841034