JAK抑制剂治疗炎症性肠病有效性及安全性的Meta分析

Efficacy and safety of JAK inhibitors in the treatment of inflammatory bowel disease:a Meta-analysis

目的评估JAK1选择性抑制剂与泛JAK抑制剂治疗炎症性肠病(inflammatory bowel disease,IBD)相比能否获得更高的有效性、安全性及评估不同剂量Tofacitinib的有效性和安全性。方法计算机检索PubMed、Cochrane Library、Web of Science、EmBase、中国知网(CNKI)、VIP、万方数据库、CBM、临床试验注册数据库中有关IBD和JAK抑制剂的文献,检索时间为建库至2020年12月。筛选出关于泛JAK抑制剂与安慰剂比较或JAK1选择性抑制剂与安慰剂比较的前瞻性随机对照试验(RCTs)的文献,再进行数据提取及分析,选择有效率和不良反应率为终点指标,通过间接比较法(ITC)比较泛JAK抑制剂与JAK1选择性抑制剂的有效性及安全性。同时比较分析Tofacitinib不同剂量组治疗IBD的有效性及安全性。结果共纳入9篇文献,共12项RCTs研究,共计活动性IBD患者3450例,包括试验组2606例,安慰剂组844例。Meta分析结果显示,泛JAK抑制剂与JAK1选择性抑制剂治疗IBD的有效性及安全性比较,差异均无统计学意义(P>0.05)。Tofacitinib 10 mg bid试验组临床反应率高于5 mg bid试验组,差异有统计学意义(RR=1.14,95%CI:1.01~1.30,Z=2.07,P=0.004);15 mg bid试验组临床反应率高于10 mg bid试验组,差异有统计学意义(RR=1.29,95%CI:1.11~1.50,Z=3.23,P=0.001),临床缓解率及不良反应率在不同剂量组之间差异无统计学意义(P>0.05)。结论泛JAK抑制剂与JAK1选择性抑制剂治疗IBD的有效性及安全性相当;Tofacitinib 15 mg bid组临床反应率优于10 mg bid组,10 mg bid组临床反应率优于5 mg bid组,临床缓解率及不良反应率在不同剂量组之间相当。

Objective To evaluate the efficacy and safety of JAK1 selective inhibitors compared with Pan JAK inhibitors in the treatment of inflammatory bowel disease(IBD),and to evaluate the efficacy and safety of different doses of Tofacitinib.Methods PubMed,Cochrane Library,Web of Science,EmBase,CNKI,VIP,WanFang database,CBM and clinical trial registration database for literatures related to IBD and JAK inhibitors from the establishment of the database to Dec.2020 were searched.To screen out the literature of prospective randomized controlled trials(RCTs)on the comparison of Pan JAK inhibitors and placebo or JAK1 selective inhibitors and placebo,and then extract and analyze the data,select the effective rate and adverse reaction rate as the endpoint indicators,and compare the relative efficacy and safety of Pan JAK inhibitors and JAK1 selective inhibitors by indirect comparison(ITC).At the same time,the relative efficacy and safety of different doses of Tofacitinib in the treatment of IBD were compared and analyzed.Results A total of 9 articles,12 RCTs and 3450 cases of active IBD were included,including 2606 cases in the experimental group and 844 cases in the placebo group.Meta-analysis showed that there was no significant difference in efficacy and safety between Pan JAK inhibitor and JAK1 selective inhibitor in the treatment of IBD(P>0.05).The clinical response rate of Tofacitinib 10 mg bid group was higher than that of 5 mg bid group(RR=1.14,95%CI:1.01-1.30,Z=2.07,P=0.004);the clinical response rate of Tofacitinib 15 mg bid group was higher than that of 10 mg bid group(RR=1.29,95%CI:1.11-1.50,Z=3.23,P=0.001).There was no significant difference in clinical remission rate and adverse reactions between different doses groups(P>0.05).Conclusion The efficacy and safety of Pan JAK inhibitor and JAK1 selective inhibitor in the treatment of IBD are similar.The clinical response rate of Tofacitinib 15 mg bid group is better than that of 10 mg bid group,the clinical response rate of 10 mg bid group is better than that of 5 mg bid group,and the clinical remission rate and adverse reaction rate are similar between different doses groups.