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中国循证儿科杂志

中国循证儿科杂志 ›› 2023, Vol. 18 ›› Issue (1): 21-26.DOI: 10.3969/j.issn.1673-5501.2023.01.003

• 论著 • 上一篇    下一篇

激素敏感型肾病综合征儿童利妥昔单抗治疗不良事件的系统评价/Meta分析

邵蕾霖1a，刘佳璐1a，陈秋霞2，沈茜1a，张崇凡1b，王慧珊1b，王颖雯1c，张爱华2，夏正坤3，徐虹1a   

  1.  1 复旦大学附属儿科医院上海，201102，a 肾脏科，上海市肾脏发育和儿童肾脏病研究中心，b 复旦大学GRADE中心，c 护理部；2 南京医科大学附属南京儿童医院肾脏科南京，210093；3 中国人民解放军东部战区总医院南京，210002

  • 收稿日期:2023-04-04 修回日期:2023-04-04 出版日期:2023-02-25 发布日期:2023-02-25
  • 通讯作者: 徐虹，张爱华

Adverse events of rituximab for children with steroid-sensitive nephrotic syndrome: A systematic review and meta-analysis

SHAO Leilin1a, LIU Jialu1a, CHEN Qiuxia2, SHEN Qian1a, ZHANG Chongfan1b,  WANG Huishan1b, WANG Yingwen1c, ZHANG Aihua2, XIA Zhengkun3, XU Hong1a   

  1. 1 Children's Hospital of Fudan University, Shanghai 201102, China, a Department of Nephrology, Shanghai Kidney Development and Pediatric Kidney Disease Research Center, b Fudan University GRADE Center, c Department of Nursing; 2 Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing 210093, China; 3 General Hospital of the Eastern Theater of the Chinese People's Liberation Army, Nanjing 210002, China
  • Received:2023-04-04 Revised:2023-04-04 Online:2023-02-25 Published:2023-02-25
  • Contact: XU Hong, email: hxu@shmu.edu.cn；ZHANG Aihua, email: bszah@163.com

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摘要： 背景：近20多年来利妥昔单抗（RTX）应用于儿童激素敏感型肾病综合征（SSNS）的治疗较其他免疫抑制剂有更好的疗效，但仍需要积累不良事件的报告情况。 目的：了解儿童SSNS应用RTX治疗后的不良事件。 设计：系统评价/Meta分析。 方法：检索PubMed、Embase、Cochrane、Scopus和中国生物医学文献服务系统数据库，检索时间为建库至2022年6月26日，以SSNS、RTX构建中英文数据库检索式。同一篇文献初筛、全文筛选和证据提取均由2人完成，有争议和不确定的文献由第3人复核。纳入至少1组干预措施使用RTX治疗1~22岁SSNS患儿的研究。 主要结局指标：不良事件发生率。 结果：共纳入47篇文献（中文5篇，英文42篇），7篇双臂干预研究［RCT 5篇，非随机对照试验2篇］和40篇病例系列报告。RTX组较安慰剂或常规免疫抑制剂（对照组）治疗SSNS患儿不良事件发生率（130/184 vs 107/177）、严重不良事件发生率（14/140 vs 9/122）和输液相关反应发生率（19/24 vs 13/24）差异均无统计学意义；感染发生率（56/80 vs 41/62）差异有统计学意义（OR=3.99, 95%CI:1.23~12.97）。RTX治疗SSNS病例系列报告中，不良事件发生率59%（95%CI:55%~63%），严重不良事件发生率7%（95%CI:6%~9%），输液反应发生率31%（95%CI:28%~35%），感染发生率21%（95%CI:18%~24%），血清病发生率5%（95%CI:2%~10%），同时报告外周血中性粒细胞减少和缺乏的研究中，中性粒细胞减少发生率9%（95%CI:5%~17%）、缺乏发生率4%（95%CI:2%~10%），针对低IgG血症研究的低IgG血症发生率为51%（95%CI:42%~60%）。 结论：RTX治疗SSNS未增加不良事件、严重不良事件和感染的发生率，低IgG血症和血清病值得关注。

关键词: 儿童, 激素敏感型肾病综合征, 利妥昔单抗, 不良事件, 安全性

Abstract: Background：Over the past 20 years, rituximab (RTX) has shown better efficacy than other immunosuppressants in the treatment of children with steroid-sensitive nephrotic syndrome (SSNS), but reports of adverse events still need to be accumulated. Objective：To understand the adverse events of rituximab for children with SSNS. Design：Systematic review and meta-analysis. Methods：PubMed, Embase, Cochrane, Scopus and Chinese Biology Medicine databases were searched from the inception to June 26, 2022, with the keywords of SSNS and RTX. The preliminary screening, full text screening and data extraction were all completed by the same two reviewers. Unsure or controversial literature was submitted to a third reviewer. At least one RTX intervention for children aged between 1 and 22 years with SSNS was included. Main outcome measures：The incidences of adverse events. Results：A total of 47 studies (5 in Chinese and 42 in English) were included in the analysis, including 7 doublearm intervention studies (5 randomized controlled trials, 2 nonrandomized study) and 40 case series reports. Comparing RTX with placebo or conventional immunosuppressants (control group) in SSNS children, there were no statistically significant differences in the incidences of adverse events (7 studies, 130/184 vs 107/177), serious adverse events (4 studies, 14/140 vs 9/122), infusion reaction (1 study, 19/24 vs 13/24) and infection (2 studies, 33/56 vs 23/38). In case series reports of SSNS children treated with RTX, the incidences of adverse events, serious adverse events, infusion reaction, infection and serum sickness were 59 percent (95%CI: 55 percent to 63percent), 7 percent (95%CI: 6 percent to 9 percent),31 percent (95%CI: 28 percent to 35 percent), 21 percent (95%CI: 18 percent to 24 percent) and 5 percent (95%CI: 2 percent to 10 percent), respectively. Studies reporting both neutropenia and agranulocytosis revealed the incidence of neutropenia was 9 percent (95%CI: 5 percent to 17 percent) and the incidence of agranulocytosis was 4 percent (95%CI: 2 percent to 10 percent). Studies focusing on hypogammaglobulinemia revealed the incidence of hypogammaglobulinemia was 51 percent (95%CI: 42 percent to 60 percent). Conclusions：RTX treatment of SSNS did not increase the incidences of adverse events, serious adverse events and infection, but hypogammaglobulinemia and serum sickness should be of concern.

Key words: Children, Steroid-sensitive nephrotic syndrome, Rituximab, Adverse events, Safety