沙立芦单抗治疗类风湿关节炎疗效和安全性的Meta分析

Efficacy and safety of sarilumab in patients with rheumatoid arthritis: a meta-analysis

目的评价白细胞介素-6 (IL-6)抑制剂沙立芦单抗治疗类风湿关节炎(RA)的疗效和安全性。方法计算机检索PubMed、 Embase、 Web of Science、美国食品和药物管理局(FDA)网站、临床试验注册网站、 Cochrane图书馆、中国知网、万方和维普数据库,检索时间为建库至2019年2月28日。筛选研究沙立芦单抗治疗RA的疗效和安全性的随机对照试验(RCT)。采用RevMan5.2和Stata 14.0进行Meta分析。结果共纳入6项RCT,总计2 932例患者。在疗效指标方面,沙立芦单抗组RA病情缓解20%、50%、 70%的受试者人数(ACR20、 ACR50、 ACR70)均显著高于对照组(分别为RR=1.75, 95%CI:1.45～2.13, P <0.000 01; RR=1.90, 95%CI:1.60～2.26, P <0.000 01; RR=3.15, 95%CI:2.46～4.04, P <0.000 01);沙立芦单抗组健康评估问卷-残疾指数(HAQ-DI)和C反应蛋白计算的RA病情活动度评价表(DAS28-CRP)评分显著低于对照组(分别为WMD=-0.27, 95%CI:-0.32～-0.23, P <0.000 01; WMD=-0.89, 95%CI:-1.13～-0.64, P <0.000 01)。在安全性方面,沙立芦单抗组不良事件发生率、严重不良事件发生率和患者因不良事件退出发生率显著高于对照组(分别为RR=1.24, 95%CI:1.14～1.36, P <0.000 01; RR=1.33, 95%CI:1.03～1.70, P=0.03; RR=2.28, 95%CI:1.78～2.94,P <0.000 01)。沙立芦单抗组的死亡风险与对照组相似(P=0.36)。结论沙立芦单抗治疗RA患者疗效肯定,但安全性需做进一步的确认,尚需高质量、大样本的RCT研究评估。

AIM To evaluate the efficacy and safety of interleukin-6(IL-6)inhibitor sarilumab for patients with rheumatoid arthritis(RA).METHODS PubMed,Embase,Web of Science,Food and Drug Administration(FDA)web site,clinical trials website and Cochrane library,CNKI,Wanfang,VIP databases were searched with the searching time from building the library until February 28,2019.Randomized controlled trials(RCTs)of sarilumab in the treatment of RA were collected.Meta-analysis was conducted using RevMan 5.2 software and Stata 14.0 software.RESULTS Six RCTs with 2 932 participants were included.In the aspect of efficacy,the America College of Rheumatology 20,50,70 response(ACR20,ACR50 and ACR70)of the sarilumab group was significant higher than that in the control group(RR=1.75,95%CI:1.45-2.13,P<0.000 01;RR=1.90,95%CI:1.60-2.26,P<0.000 01;RR=3.15,95%CI:2.46-4.04,P<0.000 01).Compared with the control group,the health assessment questionnaire-disability index(HAQ-DI)and 28-joint disease activity score combined with C-reactive protein level(DAS28-CRP)of the sarilumab group were significantly reduced(WMD=-0.27,95%CI:-0.32--0.23,P<0.000 01;WMD=-0.89,95%CI:-1.13--0.64,P<0.000 01).In term of safety,the incidence of adverse events,serious adverse events and withdrawal from adverse events were increased in the sarilumab group(RR=1.24,95%CI:1.14-1.36,P<0.000 01;RR=1.33,95%CI:1.03-1.70,P=0.03;RR=2.28,95%CI:1.78-2.94,P<0.000 01,respectively).The risk of death in the sarilumab group was similar to that of the control group(P=0.36).CONCLUSION Sarilumab is effective in the treatment of RA,but the safety needs to be further confirmed,which is still necessary to evaluate by high-quality,large-sample RCT studies.