Thromboembolism with Janus Kinase (JAK) Inhibitors for Rheumatoid Arthritis: How Real is the Risk?
Thromboembolism with Janus Kinase (JAK) Inhibitors for Rheumatoid Arthritis: How Real is the Risk?
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DOI：
10.1007/s40264-018-0651-5
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发表时间：
2018-07-01
期刊：
影响因子：
4.2
通讯作者：
Scott, David L.
中科院分区：
文献类型：
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作者：
Scott, Ian C.;Hider, Samantha L.;Scott, David L.
两种不同的Janus激酶（JAK）抑制剂-baricitinib和tofacitinib-有效并获准用于活动性类风湿关节炎（RA）。最近有关于这些药物潜在血栓栓塞风险的担忧。对巴西替尼的关注主要集中在临床试验结果上。根据所有公开数据，我们估计每天服用4mg巴西替尼的患者，每1000名患者年约有5次血栓栓塞风险。联邦药物管理局不良事件报告系统（FAERs）的分析引起了对托法替尼的关注。这些证据表明，虽然不是肺栓塞或静脉血栓形成，但肺血栓形成的风险增加。观察性研究表明，在普通人群和非类风湿性关节炎对照组中，每1000名患者年发生1至4例血栓栓塞事件。在类风湿性关节炎中，血栓栓塞风险增加到每1000名患者年3 - 7例。生物制剂和改善疾病的抗风湿药物（DMARDs）对疾病风险的影响似乎很小，血栓栓塞事件的数量在每1000名患者年4至8例之间。在短期内，需要公布JAK抑制剂试验中血栓栓塞事件的全部细节。由于血栓栓塞事件的数量很少，而且参加试验的患者并不能代表可能接受JAK抑制剂治疗的所有RA患者，因此这一信息不太可能提供明确的答案。因此，从长期来看，需要大规模的观察性研究来准确量化JAK抑制剂和其他用于治疗RA的药物所导致的血栓栓塞风险，并将其与RA本身及其合并症所导致的风险区分开来。
Two different Janus kinase (JAK) inhibitors-baricitinib and tofacitinib-are effective and licensed in active rheumatoid arthritis (RA). There have been recent concerns about potential thromboembolic risks with these drugs. Concerns about baricitinib focus on clinical trial findings. Using all publically available data, we estimate thromboembolic risks are approximately five events per 1000 patient years with 4 mg baricitinib daily. Concerns about tofacitinib have been raised by analyses of the Federal Drug Administration Adverse Event Reporting System (FAERs). These show some evidence of increased risks of pulmonary thrombosis, though not pulmonary embolism or venous thrombosis. Observational studies suggest in the general population and non-RA controls there are one to four thromboembolic events per 1000 patient years. In RA, thromboembolic risks increase to three to seven per 1000 patient years. The impact of biologics and disease-modifying anti-rheumatic drugs (DMARDs) on disease risk appears minimal, and the number of thromboembolic events is between four and eight per 1000 patient years. In the short term, full details of thromboembolic events in trials of JAK inhibitors need to be published. As the numbers of thromboembolic events will be small and patients enrolled in trials are not representative of all RA patients who may receive JAK inhibitors, this information is unlikely to provide definitive answers. Consequently, in the longer term, large observational studies are needed to accurately quantify thromboembolic risks attributable to JAK inhibitors and other drugs used to treat RA, and differentiate these from risks attributable to RA itself and its comorbidities.