Agrawal Manasi, Kim Eun Soo, Colombel Jean-Frederic
Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York NY, USA.
Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.
J Crohns Colitis. 2020 Aug 1;14(Supplement_2):S755-S760. doi: 10.1093/ecco-jcc/jjaa017.
Janus kinase inhibitors [JAKi] are a new class of small molecule drugs that modulate inflammatory pathways by blocking one or more JAK receptors, and are increasingly being used in the treatment of immune-mediated diseases. Tofacitinib, a non-selective JAKi, is now approved for moderate-to-severe ulcerative colitis [UC] that is refractory or intolerant to tumour necrosis factor inhibitors [TNFi]. Whereas tofacitinib is associated with the advantages of oral administration, rapid onset of action, and lack of immunogenicity over TNFi, there are many safety considerations to take into account such as the risk of thromboembolism, infections, and hyperlipidaemia: each with specific nuances pertaining to prevention and monitoring strategies. Considerations such as pregnancy, breastfeeding, and history of malignancy also are to be navigated with utmost caution, given that very few data are available for guidance. With the use of JAKi in the real world progressively over time, safety implications will become more lucid, including caveats pertaining to JAK selectivity and gut-selective JAKi, as well as mechanistic data pertaining to adverse effects. This Viewpoint serves as a practical guide for clinicians managing inflammatory bowel disease [IBD] patients to navigate safety concerns around JAKi, including preventive and monitoring strategies.
Janus激酶抑制剂（JAKi）是一类新型小分子药物，通过阻断一种或多种JAK受体来调节炎症通路，越来越多地用于治疗免疫介导的疾病。托法替布是一种非选择性JAKi，目前已被批准用于治疗对肿瘤坏死因子抑制剂（TNFi）难治或不耐受的中重度溃疡性结肠炎（UC）。虽然托法替布具有口服给药、起效迅速以及相对于TNFi缺乏免疫原性等优点，但仍有许多安全问题需要考虑，如血栓栓塞、感染和高脂血症的风险：每种风险在预防和监测策略方面都有特定的细微差别。鉴于可供指导的数据非常少，对于怀孕、母乳喂养和恶性肿瘤病史等问题也需要极其谨慎地处理。随着JAKi在现实世界中的使用逐渐增加，其安全性影响将变得更加清晰，包括与JAK选择性和肠道选择性JAKi相关的注意事项，以及与不良反应相关的机制数据。本观点为管理炎症性肠病（IBD）患者的临床医生提供了一份实用指南，以应对围绕JAKi的安全问题，包括预防和监测策略。
