肛周手术和抗肿瘤坏死因子-α单克隆抗体序贯治疗成人克罗恩病肛瘘的疗效和安全性的Meta分析

Efficacy and safety of perianal surgery plus anti-TNF-alpha monoclonal antibody sequential treatment in adult patients with perianal fistula of Crohn's disease: a meta-analysis

目的 比较抗肿瘤坏死因子(TNF)-α单克隆抗体、肛周手术及肛周手术后抗TNF-α单克隆抗体序贯方式治疗成人克罗恩病(CD)肛瘘的疗效及安全性.方法 检索PubMed、EMBASE和Cochrane等数据库,查找相关的临床研究(试验性研究及观察性研究).研究的首要观察目标为肛瘘的应答率,次要观察目标为肛瘘复发率.结果 8个对照研究被纳入,包括3项前瞻性研究和5项回顾性研究,共纳入研究对象688例.Meta分析结果显示,序贯治疗组相比于单纯肛周手术组未显著提高肛瘘愈合率(78.5％比65.2％,OR=2.21,95％ CI:0.83～5.90,P=0.11);分层分析发现两组在肛瘘完全愈合率及部分愈合率之间差异无统计学意义,但序贯治疗组的肛瘘复发率较单纯肛周手术组低(20.8％比76.1％,OR=0.10,95％ CI:0.03 ～ 0.37,P=0.0006).序贯治疗组与单纯抗TNF-α单克隆抗体组的肛瘘愈合率及不良反应发生率差异无统计学意义,但前者预防瘘管复发的风险较低(30.0％比69.2％,OR=0.24,95％ CI:0.06～0.93,P=0.04,n=57).序贯治疗常见的不良反应有头疼、轻微胸痛、轻微输液反应、过敏反应、肌肉乏力、腹痛及败血症,主要为抗TNF-α单克隆抗体相关的不良反应.结论 肛周手术和抗TNF-α单克隆抗体的序贯治疗并未显著提高肛瘘愈合率,但相比于单一治疗方法可降低肛瘘复发率,同时并不增加不良反应发生率.

Objective To compare the efficacy and safety of perianal surgery plus anti-TNF-alpha monoclonal antibody sequential treatment with single perianal surgery and anti-TNF-alpha administration in adult patients with perianal fistula of Crohn's disease (CD).Methods PubMed,EMBASE and Cochrane database were searched to find relevant clinical studies (experimental and observational studies).The primary outcome of the study was the response rate of perianal fistula,and the secondary target was the recurrence rate of perianal fistula.Results Eight control studies were enrolled,including three prospective studies and five retrospective studies with a total of 688 subjects.Meta-analysis showed that the sequential treatment group did not significantly improve the perianal fistula healing rate compared with the perianal surgery group (78.5％ vs.65.2％,OR =2.21,95％ CI:0.83 ～ 5.90,P =0.11).There was no significant difference between two groups in the complete healing rate and partial healing rate of perianal fistula,but the recurrence rate of perianal fistula in sequential treatment group was lower than that in perianal surgery group (20.8％ vs.76.1％,OR =0.10,95％ CI:0.03 ～ 0.37,P =0.0006).There was no significant difference in perianal fistula healing rate and the incidence of adverse reactions between sequential treatment group and anti-TNF-α monoclonal antibody group,but the former had a lower risk of preventing fistula recurrence (30.0％ vs.69.2％,OR =0.24,95％ CI:0.06 ～ 0.93,P =0.04,n =57).Common adverse reactions in sequential treatment group included headache,mild chest pain,mild infusion reaction,allergic reaction,muscle weakness,abdominal pain and sepsis,which were main anti-TNF-α monoclonal antibody-related adverse reactions.Conclusion Sequential treatment does not significantly improve the perianal fistula healing rate,but reduces the recurrence rate of perianal fistula compared to single treatments,while not increasing the incidence of adverse reactions.