频复发/激素依赖肾病综合征儿童利妥昔单抗治疗1年以上随访情况的系统评价/Meta分析  

Over 1-year follow-up for children with frequently relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome after receiving treatment of rituximab:A systematic review and meta-analysis

作　　者：刘佳璐 陈秋霞[4] 邵蕾霖 张崇凡[2] 王慧珊 王颖雯 张爱华[4] 夏正坤 沈茜 徐虹 LIU Jialu;CHEN Qiuxia;SHAO Leilin;ZHANG Chongfan;WANG Huishan;WANG Yingwen;ZHANG Aihua;XIA Zhengkun;SHEN Qian;XU Hong(Department of Nephrology,Shanghai Kidney Development and Pediatric Kidney Disease Research CenterChildren's Hospital of Fudan University,Shanghai 201102,China;Fudan University GRADE CenterChildren's Hospital of Fudan University,Shanghai 201102,China;Department of Nursing,Children's Hospital of Fudan University,Shanghai 201102,China;Department of Nephrology,Children's Hospital of Nanjing Medical University,Nanjing 210093,China;General Hospital of the Eastern Theater of the Chinese People's Liberation Army,Nanjing 210002,China)

机构地区：[1]复旦大学附属儿科医院肾脏科,上海市肾脏发育和儿童肾脏病研究中心,上海201102 [2]复旦大学附属儿科医院复旦大学GRADE中心,上海201102 [3]复旦大学附属儿科医院护理部,上海201102 [4]南京医科大学附属南京儿童医院肾脏科南京,210093 [5]中国人民解放军东部战区总医院,南京210002

出　　处：《中国循证儿科杂志》2023年第1期13-20,共8页Chinese Journal of Evidence Based Pediatrics

基　　金：申康促进市级医院临床技能与临床创新,三年行动计划,研究型医师创新转化能力培训项目:SHDC2022CRD018;国家重点研发计划课题编号:2021YFC2500202;复旦大学附属儿科医院重点发展项目疑难重症诊治中心:EK2022ZX01。

摘　　要：背景权威指南和共识均推荐将利妥昔单抗(RTX)应用于儿童激素敏感型肾病综合征(SSNS)中频复发/激素依赖肾病综合征(FRNS/SDNS)的治疗,但仍存在临床适应证不统一、治疗和随访方案多样等问题。目的了解RTX首疗程治疗缓解期FRNS/SDNS随访1年以上复发和激素使用情况结局。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,从建库至2022年6月26日,以SSNS、FRNS、SDNS和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人复核审查。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RTX干预后随访≥1年的复发率、首次复发时间,激素累积剂量和停用比例。结果符合本文临床结局的文献26篇(RCT 8篇、非随机对照试验1篇、队列研究8篇、病例系列报告9篇),中文文献1篇,英文文献25篇。基于FRNS/SDNS病例的随访≥1年复发率的9项研究的Meta分析显示,RTX较对照组复发率下降了78%(OR=0.22,95%CI:0.09~0.53),在FRNS/SDNS+(RTX干预前已使用其他免疫抑制剂)亚组病例中,RTX较对照组复发率下降了67%(OR=0.33,95%CI:0.12~0.94),在FRNS/SDNS-(RTX干预前未使用其他免疫抑制剂)亚组病例中,RTX-(不联用其他并免疫抑制剂)较对照组复发率下降了85%(OR=0.15,95%CI:0.03~0.68)。基于20项研究的Meta分析显示,RTX复发率42%(95%CI:32%~53%)。基于FRNS/SDNS+随访≥1年首次复发时间的9项研究的Meta分析显示,首次复发时间9.89(95%CI:7.14~12.65)月。基于FRNS/SDNS-开始干预至随访≥1年中位首次复发时间的3项研究的Meta分析显示,RTX(1~2剂)较对照组中位首次复发时间长20 d,中位生存比(MSR)为0.69(95%CI:0.52~0.87)。基于FRNS/SDNS的12个月激素累积剂量减少结局的4项研究的Meta分析显示,RTX较对照组年激素累积剂量减少明显,差异有统计学意Background Authoritative clinical practice guidelines and expert consensus have recommended the use of rituximab(RTX)in the treatment of children with frequent relapsing/steroid-dependent nephrotic syndrome(FRNS/SDNS)of steroid-sensitive nephrotic syndrome(SSNS).However,there is a discrepancy in terms of clinical indications,treatment,and follow-up protocols.Objective To comprehensively examine relapse and steroid therapy during over one year follow-up in patients diagnosed with FRNS/SDNS who were administered the initial course of RTX while being in remission.Design Systematic review and meta-analysis.Methods Keywords of SSNS,FRNS,SDNS,and RTX were used to search China Biology Medicine Database,PubMed,Embase,Scopus,and Cochrane from the inception to June 26,2022.The preliminary and full-text screening were conducted by two independent reviewers,who also extracted the relevant data.Unsure or controversial literature underwent a third-party review.At least one RTX intervention for children aged between 1 and 22 years with SSNS was included.Main outcome measures The frequency of relapse,time to the first relapse,cumulative steroid dosage,and percentage of patients who withdrew from steroids in those who were followed-up for more than 1 year after receiving RTX intervention.Results A total of 26 studies(1 in Chinese and 25 in English)were eligible including 8 randomized controlled trials(RCT),1 non-randomized study of interventions(NRSI),8 cohort studies,and 9 case series reports.Two subgroups were defined as FRNS/SDNS+group in which immunosuppressants were used before RTX intervention and FRNS/SDNS-group in which no other immunosuppressants were used before RTX intervention.Meta-analysis of 9 studies on the relapse rate of FRNS/SDNS during at least 1-year follow-up showed a 78%reduction in the relapse rate of RTX compared to the control group(OR=0.22,95%CI:0.09 to 0.53).In FRNS/SDNS+group,RTX reduced the relapse rate by 67%compared to the control group(OR=0.33,95%CI:0.12 to 0.94).In FRNS/SDNS-group,RTX reduced the

关 键 词：肾病综合征 利妥昔单抗 免疫抑制剂 复发 激素 

分 类 号：R726.9[医药卫生—儿科]