Jerry L Pettis Memorial Veterans Hospitals Loma Linda Va Medical Center, Loma Linda, CA, USA.
Midwestern University Chicago College of Osteopathic Medicine, Downers Grove, IL, USA.
Expert Rev Clin Immunol. 2023 Jul-Dec;19(9):1075-1089. doi: 10.1080/1744666X.2023.2214728. Epub 2023 May 24.
Janus Kinase inhibitors (JAKi) are a new class of oral therapies for the treatment of moderate-severe ulcerative colitis with additional potential for the treatment of moderate-severe Crohn's disease. In contrast to biologic therapies JAKi provide the opportunity for non-immunogenic once or twice daily oral therapies.
Janus Kinase inhibitors for the treatment of ulcerative colitis and Crohn's disease based on mechanism of action, pharmacokinetics, clinical trial and real-world data regarding safety and efficacy; focusing on regulatory approvals in the U.S. and Europe.
Janus Kinase inhibitors are considered among the 'advanced therapies' for IBD and are approved for the treatment of moderate to severe ulcerative colitis in adults with pending approvals for Crohn's disease in the U.S. JAKi offer non-immunogenic, oral options for patient not responding to other conventional agents but, have been 'restricted' by the FDA to patients with inadequate response to TNF blockers. JAKi offer rapidly acting oral alternatives to biologic agents for moderate-severe ulcerative colitis where the risks of cardiovascular and thrombotic events noted in rheumatoid arthritis have not been observed in IBD clinical trials. Nevertheless, monitoring of infections (primarily herpes zoster) and risk factors for cardiovascular and thrombotic complications is appropriate.
Janus 激酶抑制剂(JAKi)是一类新型的口服治疗药物,可用于治疗中重度溃疡性结肠炎,并有潜力治疗中重度克罗恩病。与生物疗法不同,JAKi 提供了非免疫原性的每日一次或两次口服治疗的机会。
基于作用机制、药代动力学、临床试验和安全性及疗效的真实世界数据,探讨 JAKi 治疗溃疡性结肠炎和克罗恩病的用途;重点关注美国和欧洲的监管批准情况。
Janus 激酶抑制剂被认为是 IBD 的“先进疗法”之一,已被批准用于治疗成人中重度溃疡性结肠炎,在美国克罗恩病的批准正在等待中。JAKi 为对其他常规药物无反应的患者提供了非免疫原性的口服选择,但 FDA 将其限制在对 TNF 阻滞剂反应不足的患者中。JAKi 为中重度溃疡性结肠炎提供了快速起效的口服替代生物制剂,在类风湿关节炎中观察到的心血管和血栓事件风险并未在 IBD 临床试验中观察到。然而,仍需监测感染(主要是带状疱疹)和心血管及血栓并发症的风险因素。