来源：风湿病与关节炎,2018,7（8）:27-33,40.

白细胞介素类生物制剂治疗类风湿关节炎安全性的Meta分析

（循证研究）

魏婷婷，付凌雨，辛芳冉，陈　萌

　　【摘　要】目的：通过系统评价白细胞介素（IL）类生物制剂治疗类风湿关节炎的安全性，以指导临床用药选择，有效减少IL类生物制剂相关不良反应的发生。方法：计算机检索PubMed、EMbase、The Cochrane library、中国知网、中国生物医学文献数据库、维普及万方等数据库，搜集有关托珠单抗和阿那白滞素2种常用IL类生物制剂治疗类风湿关节炎的随机对照试验（RCT），检索时间为数据库建立至2018年1月。由2位评价员独立筛选文献、提取资料并评价纳入文献的方法学质量后，利用RevMan 5.0软件对各研究结果进行Meta分析。结果：共纳入12个RCT，包括7405例患者。Meta分析结果显示，IL生物制剂组的不良事件发生率（RR = 1.09，95%CI = ［1.02，1.17］，P = 0.01）和感染发生率（RR = 1.09，95%CI = ［1.01，1.18］，P = 0.03）均高于对照组。亚组分析显示，不同种类IL类生物制剂安全性不一，托珠单抗组的不良事件发生率（RR = 1.09，95%CI = ［1.01，1.19］，P = 0.03）及感染发生率（RR = 1.19，95%CI = ［1.01，1.22］，P = 0.03）均显著高于对照组，而阿那白滞素组的安全性与对照组比较，差异无统计学意义（RR = 1.16，95%CI = ［0.89，1.53］，P = 0.28）；不同剂量IL类生物制剂安全性不一，高剂量使用IL抑制剂致不良事件发生率（RR = 1.07，95%CI = ［1.01，1.15］，P = 0.004）及严重感染反应率（RR = 1.62，95%CI = ［1.05，2.51］，P = 0.03）均高于对照组，中低剂量组仅不良反应发生率高于对照组（RR = 1.08，95%CI = ［1.03，1.15］，P = 0.004）。结论：IL类生物制剂治疗类风湿关节炎与安慰剂或改善病情抗风湿药相比，可能会增加不良事件发生率、感染发生率以及严重感染发生率，但尚需后续的RCT做进一步探讨。

　　【关键词】　关节炎，类风湿；白细胞介素；安全性；Meta分析；随机对照试验

Meta-analysis of the Safety of Interleukin Biological Agents in the Treatment of Rheumatoid Arthritis

WEI Ting-ting,FU Ling-yu,XIN Fang-ran,CHEN Meng

　　【ABSTRACT】Objective:To evaluate the safety of interleukin（IL）biological agents in the treatment of rheumatoid arthritis（RA）in order to guide the choice of clinical medication and reduce the occurrence of adverse reactions associated with IL biological agents.Methods:PubMed,EMbase,The Cochrane Library,CNKI,CBM,VIP,WANFANG and other databases were searched to collect randomized controlled trials（RCT）of treating rheumatoid arthritis with tropizumab and anakinra（from the establishment of databases to January 2018）.After two reviewers independently screened the literature,extracted the data and evaluated the methodological quality of the included literature,the results were analyzed using RevMan 5.0 software.Results:A total of 12 RCT were included,including 7405 patients.Meta-analysis showed that the incidence of adverse events was（RR = 1.09,95% CI = ［1.02,1.17］,P = 0.01）and the infection rate was（RR = 1.09,95%CI = ［1.01,1.18］,P = 0.03）in the IL biological agent group,which were higher than those in the control group.Analysis for the subgroups showed that the safety of different kinds of IL biologicals was different.The incidence of adverse events was（RR = 1.09,95%CI = ［1.01,1.19］,P = 0.03）and the incidence of infection rate was（RR = 1.19,95%CI = ［1.01,1.22］,P = 0.03）in the tropizumab group,which were significantly higher than those in the control group,while the difference of safety between the anakinra group and the control group had no significant difference（RR = 1.16,95%CI = ［0.89,1.53］,P = 0.28）.The safety of different doses of IL biologicals was different,and the incidence of adverse events of high dose was（RR = 1.07,95%CI = ［1.01,1.15］,P = 0.004）and the severe infection response rate was（RR = 1.62,95%CI =［1.05，2.51］,P = 0.03）,which were higher than those in the control group,and only the incidence of adverse reactions in the low-dose or medium-dose group was higher than that in the control group（RR = 1.08,95%CI = ［1.03,1.15］,P = 0.004）.Conclusion:Compared with placebo or anti-rheumatic drugs,IL biological agents may increase the incidence of adverse events,infections and severe infections,but further study on RCT is needed.

　　【Keywords】 arthritis,rheumatoid;interleukin;safety;Meta-analysis;randomized controlled trial