Janus激酶抑制剂（JAKi）自2012年以来用于类风湿性关节炎（RA）的治疗，适用于尽管接受过csDMARD治疗但仍有活动性疾病的患者。临床试验表明，其疗效和安全性与生物制剂相似。最近的一项推广后试验显示了JAKi的安全问题，将对其进行评估。一项后市场美国食品和药物管理局（FDA）强制性的无盲目随机临床试验评估了托珀西替尼每天两次5和10 mg（b.i.d.）与阿达木单抗和依他普利酯在接受甲氨蝶呤背景治疗的高危心血管疾病RA患者中的应用。这是一项非劣效研究，评估了这些治疗方案对严重不良心血管事件（MACE）和恶性肿瘤的发生率。托珀西替尼两个剂量组的非劣效性未达到，托珀西替尼与TNF抑制剂相比在MACE和恶性肿瘤方面出现了数量上的增加。观察到托珀西替尼的静脉血栓栓塞（VTE）风险与剂量相关的增加。这项研究的发现导致FDA和欧洲药品管理局（EMA）限制了所有Jaki对于未能耐受TNF抑制剂的RA患者的使用。JAK抑制剂是RA的有效治疗方法。但在存在心血管风险增加和VTE风险上提出了安全性问题，因此需要进行风险分层。版权所有©2023 Wolters Kluwer Health, Inc. 保留所有权利。

Janus kinase inhibitors (JAKi) have been available for the treatment of rheumatoid arthritis (RA) since 2012 and are indicated for patients with active disease despite csDMARD therapy. Efficacy and safety, as demonstrated in the clinical trials, was similar to biologics. A recent post marketing trial suggested safety concerns with the JAKi, which will be reviewed.A post marketing Food and Drug Administration (FDA) mandated open-label randomized clinical trial of tofacitinib 5 and 10 mg twice daily (b.i.d.) compared with adalimumab and etanercept was conducted in RA patients on background methotrexate who were at a high risk for cardiovascular disease. This was a noninferiority study evaluating the incidence of major adverse cardiovascular events (MACE) and malignancy with the therapies. Noninferiority for both doses of tofacitinib was not achieved with a numerical increase in MACEs and malignancy with tofacitinib compared to the TNF inhibitors. A dose-dependent increase in venous thromboembolism (VTE) risk with tofacitinib was observed. The findings from this study resulted in the FDA and European Medicines Agency (EMA) restriction of use for all Jaki to RA patients who had failed TNF inhibitors.JAK inhibitors are effective treatments for RA. Issues have been raised regarding safety in patients with an increase in cardiovascular risk and VTE risk resulting in the need for risk stratification.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.