背景：
托法替尼是口服的JAK激酶抑制劑，可用于治療類風(fēng)濕關(guān)節(jié)炎。托法替尼可調(diào)節(jié)淋巴細(xì)胞增殖、活化和發(fā)揮功能所需的細(xì)胞因子信號。因此，使用托法替尼可抑制免疫反應(yīng)的多個方面。既往托法替尼治療類風(fēng)濕關(guān)節(jié)炎的臨床試驗中有出現(xiàn)嚴(yán)重感染的報道。然而有限的頭對頭比較研究資料尚不足以直接比較托法替尼與生物制劑，尤其是阿達(dá)木單抗之間誘發(fā)感染的情況。
方法：
對使用生物制劑治療類風(fēng)濕關(guān)節(jié)炎的隨機(jī)對照研究和長期隨訪研究進(jìn)行了系統(tǒng)性文獻(xiàn)搜索。采用隨機(jī)效應(yīng)模型評估隨機(jī)對照試驗和長期隨訪研究中的感染發(fā)生率。采用Mantel-Haenszel法比較與安慰劑之間的相對和絕對風(fēng)險。
結(jié)果：
共檢索出657條相關(guān)信息，但僅有66項隨機(jī)對照試驗和22項長期隨訪研究符合納入標(biāo)準(zhǔn)。評估的阿巴西普、利妥昔單抗、托珠單抗和腫瘤壞死因子拮抗劑的感染率分別為3.04 , 3.72 , 5.45 和4.90。III期臨床試驗中，5mg和10mg每天2次的托法替尼使用后感染發(fā)生率分別為3.02 和3.00，長期隨訪研究中托法替尼使用后的感染率分別為2.50和3.19。與安慰劑相比，每天2次5mg和10mg托法替尼發(fā)生感染的風(fēng)險比分別為2.21和2.02，風(fēng)險差異分別為0.38 %和0.40 %。
結(jié)論：
中重度活動性類風(fēng)濕關(guān)節(jié)炎患者使用托法替尼后發(fā)生嚴(yán)重感染的風(fēng)險與先前報道的生物類改善病情抗風(fēng)濕藥物發(fā)生感染的風(fēng)險相當(dāng)。
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
