Drug Management Department, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University, 20 Grzegorzecka St., 31-531, Kraków, Poland,
Clin Rheumatol. 2013 Oct;32(10):1415-24. doi: 10.1007/s10067-013-2329-9. Epub 2013 Jul 23.
The aim of the present study was to conduct a meta-analysis of the effectiveness of tofacitinib, a novel oral Janus kinase inhibitor, recently approved for the treatment of active rheumatoid arthritis in patients who have failed previous treatment with methotrexate (MTX) or other disease-modifying antirheumatic drugs (DMARDs). A systematic literature search was conducted in PubMed, EMBASE, Cochrane Library, and other databases till 3 May 2013. All included studies were analyzed with the use of the Review Manager 5.1.0. software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement protocol. Nine randomized controlled trials (RCTs) comparing tofacitinib with placebo were identified. Two of them additionally provided the comparison with adalimumab. However, only eight RCTs met the inclusion criteria for the meta-analysis. The overall results of the meta-analysis showed that tofacitinib provided a statistically significant improvement according to the response criteria (ACR20/50/70) after 12 weeks of treatment when compared to placebo (p < 0.00001). Moreover, it was demonstrated that tofacitinib was significantly superior to adalimumab in achieving the ACR50 response criteria at week 12 (p = 0.003). For the safety analysis, there were no statistically significant differences between tofacitinib-, adalimumab-, and placebo-treated patients in respect to the risk of serious adverse events or treatment discontinuation due to adverse reactions (p > 0.05). The findings of this systematic review with meta-analysis indicate that tofacitinib monotherapy or with background methotrexate provides early statistically significant and clinically important improvement in rheumatoid arthritis symptoms and has an acceptable safety profile comparable to that of placebo. The results of the present meta-analysis show that the frequency of serious adverse events was not increased after tofacitinib treatment. In addition, tofacitinib might provide an effective treatment option compared to intravenous or subcutaneous biological DMARDs, as suggested by the result of the comparison made regarding tofacitinib vs. adalimumab ACR50 response rate.
本研究旨在对托法替尼（一种新型口服 Janus 激酶抑制剂）进行荟萃分析，该药最近被批准用于治疗接受甲氨蝶呤（MTX）或其他改善病情的抗风湿药物（DMARDs）治疗失败的活动性类风湿关节炎患者。系统检索了 PubMed、EMBASE、Cochrane 图书馆和其他数据库，截至 2013 年 5 月 3 日。根据系统评价和荟萃分析的首选报告项目（PRISMA）协议，使用 Review Manager 5.1.0 软件对所有纳入的研究进行分析。共确定了 9 项比较托法替尼与安慰剂的随机对照试验（RCT）。其中两项还提供了与阿达木单抗的比较。然而，只有 8 项 RCT 符合荟萃分析的纳入标准。荟萃分析的总体结果表明，与安慰剂相比，托法替尼在治疗 12 周后根据反应标准（ACR20/50/70）显示出统计学上的显著改善（p < 0.00001）。此外，研究表明，托法替尼在第 12 周时在达到 ACR50 反应标准方面明显优于阿达木单抗（p = 0.003）。安全性分析结果显示，托法替尼组、阿达木单抗组和安慰剂组患者在严重不良事件风险或因不良反应停药方面无统计学差异（p > 0.05）。这项系统评价和荟萃分析的结果表明，托法替尼单药或与背景甲氨蝶呤联合治疗可早期显著改善类风湿关节炎症状，并具有可接受的安全性，与安慰剂相当。本荟萃分析的结果表明，托法替尼治疗后严重不良事件的发生率并未增加。此外，与静脉或皮下生物 DMARDs 相比，托法替尼可能提供了一种有效的治疗选择，这从托法替尼与阿达木单抗 ACR50 反应率的比较结果中可以看出。
