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背景： 托法替尼是口服的JAK激酶抑制剂，可用于治疗类风湿关节炎。托法替尼可调节淋巴细胞增殖、活化和发挥功能所需的细胞因子信号。因此，使用托法替尼可抑制免疫反应的多个方面。既往托法替尼治疗类风湿关节炎的临床试验中有出现严重感染的报道。然而有限的头对头比较研究资料尚不足以直接比较托法替尼与生物制剂，尤其是阿达木单抗之间诱发感染的情况。
方法： 对使用生物制剂治疗类风湿关节炎的随机对照研究和长期随访研究进行了系统性文献搜索。采用随机效应模型评估随机对照试验和长期随访研究中的感染发生率。采用Mantel-Haenszel法比较与安慰剂之间的相对和绝对风险。
结果： 共检索出657条相关信息，但仅有66项随机对照试验和22项长期随访研究符合纳入标准。评估的阿巴西普、利妥昔单抗、托珠单抗和肿瘤坏死因子拮抗剂的感染率分别为3.04 , 3.72 , 5.45 和4.90。III期临床试验中，5mg和10mg每天2次的托法替尼使用后感染发生率分别为3.02 和3.00，长期随访研究中托法替尼使用后的感染率分别为2.50和3.19。与安慰剂相比，每天2次5mg和10mg托法替尼发生感染的风险比分别为2.21和2.02，风险差异分别为0.38 %和0.40 %。
结论： 中重度活动性类风湿关节炎患者使用托法替尼后发生严重感染的风险与先前报道的生物类改善病情抗风湿药物发生感染的风险相当。
附原文： Background:Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoidarthritis (RA). Tofacitinib modulates the signaling of cytokines that areintegral to lymphocyte activation, proliferation, and function. Thus,tofacitinib therapy may result in suppression of multiple elements of theimmune response. Serious infections have been reported in tofacitinib RAtrials. However, limited head-to-head comparator data were available within thetofacitinib RA development program to directly compare rates of seriousinfections with tofacitinib relative to biologic agents, and specificallyadalimumab (employed as an active control agent in two randomized controlledtrials of tofacitinib).Methods:A systematic literature search of data frominterventional randomized controlled trials and long-term extension studieswith biologics in RA was carried out. Preferred Reporting Items for Systematicreviews and Meta-Analyses (PRISMA) consensus was followed for reporting resultsof the review and meta-analysis. Incidence rates (unique patients withevents/100 patient-years) for each therapy were estimated based on data fromrandomized controlled trials and long-term extension studies using arandom-effects model. Relative and absolute risk comparisons versus placeboused Mantel-Haenszelmethods.Results:The search produced 657 hits. In total, 66randomized controlled trials and 22 long-term extension studies met theselection criteria. Estimated incidence rates (95 % confidence intervals[CIs]) for abatacept, rituximab, tocilizumab, and tumor necrosis factorinhibitors were 3.04 (2.49, 3.72), 3.72 (2.99, 4.62), 5.45 (4.26, 6.96), and4.90 (4.41, 5.44), respectively. Incidence rates (95 % CIs) fortofacitinib 5 and 10 mg twice daily (BID) in phase 3 trials were 3.02(2.25, 4.05) and 3.00 (2.24, 4.02), respectively. Corresponding incidence ratesin long-term extension studies were 2.50 (2.05, 3.04) and 3.19 (2.74, 3.72).The risk ratios (95 % CIs) versus placebo for tofacitinib 5 and 10 mgBID were 2.21 (0.60, 8.14) and 2.02 (0.56, 7.28), respectively. Riskdifferences (95 % CIs) versus placebo for tofacitinib 5 and 10 mg BIDwere 0.38 % (?0.24 %,0.99 %) and 0.40 % (?0.22 %,1.02 %), respectively.Conclusions: In interventional studies, the risk ofserious infections with tofacitinib is comparable to published rates forbiologic disease-modifying antirheumatic drugs in patients with moderate toseverely active RA.
引自： Vibeke Strand, Sima Ahadieh, Jonathan French, et al.Systematic review and meta-analysis of seriousinfections with tofacitinib and biologic disease-modifying antirheumatic drugtreatment in rheumatoid arthritis clinical trials. Arthritis Research&Therapy201517:362DOI: 10.1186/s13075-015-0880-2
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