选择性Janus激酶1抑制药Upadacitinib和Filgotinib治疗类风湿性关节炎疗效和安全性的Meta分析
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篇名: 选择性Janus激酶1抑制药Upadacitinib和Filgotinib治疗类风湿性关节炎疗效和安全性的Meta分析
TITLE:
摘要: 目的:系统评价两种选择性Janus激酶1(JAK-1)抑制药Upadacitinib和Filgotinib治疗类风湿性关节炎的疗效和安全性,为临床治疗提供循证参考。方法:计算机检索PubMed、Medline、Embase、Cochrane图书馆、中国生物医学文献数据库、中国期刊全文数据库、万方数据和中文科技期刊数据库,检索时限均为自建库起至2019年1月,收集在甲氨蝶呤或其他抗风湿类药物的基础上,安慰剂(对照组)对比Upadacitinib或Filgotinib(试验组)治疗类风湿性关节炎的随机对照试验(RCT),进行资料提取并采用Cochrane系统评价员手册5.1.0进行质量评价后,采用Rev Man 5.3统计软件对疗效[按美国风湿病协会标准判断病情缓解20%的患者比例(ACR20)、ACR50、ACR70、28个关节疾病活动度评分(DAS28)<3.2的患者比例]和安全性[不良事件(AE)发生率、严重不良事件(SAE)发生率、感染发生率、严重感染发生率、带状疱疹发生率、肝损害发生率]进行Meta分析。结果:共纳入8项RCT,合计2 738例患者。Meta分析结果显示,试验组患者ACR20[OR=3.37,95%CI(2.80,4.05),P<0.001]、ACR50[OR=3.78,95%CI(2.98,4.78),P<0.001]、ACR70[OR=4.31,95%CI(3.05,6.09),P<0.001] 、DAS28<3.2分的患者比例[OR=3.86,95%CI(2.98,5.00),P<0.001]、AE发生率[OR=1.33,95%CI(1.11,1.61),P=0.002]和感染发生率[OR=1.43,95%CI(1.12,1.81),P=0.004]均显著高于对照组,其余指标比较差异均无统计学意义(P>0.05)。结论:JAK-1抑制药Upadacitinib和Filgotinib在提高类风湿性关节炎患者的ACR20、ACR50、ACR70、DAS28<3.2的患者比例等疗效指标方面较好;不会增加SAE、严重感染、带状疱疹与肝损害的发生率,但会增加患者AE与感染的风险。
ABSTRACT: OBJECTIVE: To evaluate the therapeutic efficacy and safety of 2 kinds of selective Janus kinase 1 (JAK-1) inhibitor Upadacitinib and Filgotinibfor in the treatment of rheumatoid arthritis, and to provide evidence-based reference for clinical treatment. METHODS: Retrieved from PubMed, Medline, Embase, the Cochrane library, CBM, CJFD, Wanfang database and VIP, RCTs about placebo (control group) versus Upadacitinib or Filgotinibfor (trial group) in the treatment of rheumatoid arthritis on the basis of methotrexate or other antirheumatic drugs were collected during the establishment of the database to Jan. 2019. Meta-analysis of therapeutic efficacy [the proportion of patients with remission rate of 20% (ACR20), ACR50, ACR70 according to the criteria of American Rheumatism Association, the proportion of patients with 28-joint disease activity score (DAS28)<3.2] and safety [the incidence of adverse event (AE), severe adverse event (SAE), infection, severe infection, herpes zoster, liver injury] were conducted by using Rev Man 5.3 software after data extraction and quality evaluation with Cochrane system evaluator manual 5.1.0. RESULTS: A total of 8 RCTs were included, involving 2 738 patients. Meta-analysis showed that the proportion of patients with ACR20 [OR=3.37,95%CI(2.80,4.05),P<0.001], ACR50 [OR=3.78,95%CI(2.98,4.78),P<0.001] and ACR70 [OR=4.31,95%CI(3.05,6.09),P<0.001], the proportion of patients with DAS28<3.2 [OR=3.86,95%CI(2.98,5.00),P<0.001], the incidence of AE [OR=1.33,95%CI(1.11,1.61), P=0.002], the incidence of infection [OR=1.43,95%CI(1.12,1.81),P=0.004] in trial group were significantly higher than control group; there was no statistical significance in other indexes (P>0.05). CONCLUSIONS: JAK-1 inhibitors Upadacitinib and Filgotinib can improve the effect indexes of ACR20, ACR50 and ACR70 and the proportion of patients with DAS28<3.2 of rheumatoid arthritis patients; it can not increase the incidence of SAE, severe infection, herpes zoster, liver injury, but can increase the risk of AE and infection.
期刊: 2019年第30卷第15期
作者: 李世琴,李亚玲,黄毅岚,叶云,高珊,钟志容,王述蓉
AUTHORS: LI Shiqin,LI Yaling,HUANG Yilan,YE Yun,GAO Shan,ZHONG Zhirong,WANG Shurong
关键字: 选择性Janus激酶1抑制药; Upadacitinib; Filgotinib;类风湿性关节炎; Meta分析
KEYWORDS: Selective Janus kinase 1 inhibitor; Upadacitinib; Filgotinib; Rheumatoid arthritis; Meta-analysis
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