Janus激酶抑制剂巴瑞替尼治疗类风湿关节炎疗效的Meta分析

Efficacy of Janus kinase inhibitor baricitinib for patients with rheumatoid arthritis: a meta-analysis

目的系统评价Janus激酶(JAK)抑制剂巴瑞替尼治疗类风湿关节炎的有效性和安全性。方法检索Pub Med、EMbase、Cochrane Library、Web of Science、CBM、Wanfang Data、CNKI、维普数据库,收集巴瑞替尼的随机、对照临床试验,检索时间从建库至2017年6月,评价纳入研究的质量和偏倚风险,通过Rev Man 5.3软件进行疗效和安全性的Meta分析,并对疗效及安全性的各项重要结局指标进行敏感性分析。结果共纳入符合标准的6个临床研究,共3 546例患者。Meta分析结果显示:与安慰剂组相比,巴瑞替尼2 mg组在美国风湿病学会(ACR)标准判断病情缓解20%患者比率(ACR20)、ACR标准判断病情缓解50%患者比率(ACR50)、ACR标准判断病情缓解70%患者比率(ACR70)方面分别为[OR=2.81,95%CI(2.10,3.76),P<0.000 01]、[OR=3.23,95%CI(2.20,4.76),P<0.000 01]、[OR=8.16,95%CI(4.00,16.68),P<0.000 01];巴瑞替尼4 mg组在ACR20、ACR50、ACR70方面分别为[OR=3.16,95%CI(2.68,3.74),P<0.000 01]、[OR=3.34,95%CI(2.45,4.55),P<0.000 01]、[OR=4.42,95%CI(2.50,7.82),P<0.000 01]。巴瑞替尼2 mg组与4 mg组比较,在ACR20、ACR50、ACR70方面均无显著差异(P>0.05)。安全性方面,与安慰剂相比,巴瑞替尼不增加因不良事件中断试验的发生率和严重感染发生率(均P>0.05),但增加不良事件发生率(P=0.000 5)、感染发生率(P=0.000 2)和带状疱疹发生率(P=0.01)。结论巴瑞替尼治疗类风湿关节炎疗效显著,但会增加感染及带状疱疹的不良反应。

AIM To systematically estimate the effectiveness and safety of Janus kinase（JAK） inhibitorbaricitinib in treating pati ents with rheumatoid arthritis. METHODS The randomized controlled trials（ RCTs）of baricitinib for patients with rheumatoid arthritis were searched from Pub Med, EMbase, Cochrane Library,Web of Science, CBM, Wanfang Data, CNKI and VIP Databases and collected from inception to June 2017.Bias risk of RCTs and quality of documents were evaluated. All data were analyzed with Rev Man 5.3 software,and the important outcomes of efficacy and safety were assessed by sensitivity analysis. RESULTS Six RCTs involving 3 546 patients were included. Compared with placebo group, Meta-analysis showed that the American College of Rheumatology 20% response（ ACR20）, the American College of Rheumatology 50% response（ ACR50）, and the American College of Rheumatology 70% response（ ACR70） in the baricitinib 2 mg group were（OR = 2.81, 95%CI（2.10, 3.76）, P〈0.000 01）,（OR = 3.23, 95%CI（2.20, 4.76）, P〈0.000 01）,（OR = 8.16, 95%CI（4.00, 16.68）, P〈0.000 01）. The ACR20, ACR50, and ACR70 in the baricitinib 4 mg group were（OR = 3.16, 95%CI（2.68, 3.74）, P〈0.000 01）,（OR = 3.34, 95%CI（2.45, 4.55）, P〈0.000 01）,（OR = 4.42, 95%CI（2.50, 7.82）, P〈0.000 01）. Whether the dose of baricitinib was 2 mg or4 mg, and there was no significant difference between the two different dose groups（ P〈0.05）. In terms of safety, no significant difference was observed in incidence of discontinuation due to adverse events and in incidence of severe infections（ P〈0.05）. The incidence of adverse events（ P = 0.000 5）, the incidence of infection（P = 0.000 2） and the incidence of herpes zoster（P = 0.01） with baricitinib were significantly higher than with placebo. CONCLUSION Baricitinib is significantly effective in the treatment of rheumatoid arthritis but increases the incident of infection and herpes zoster.