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用于炎症性肠病的JAK抑制剂:最新进展

JAK inhibitors for inflammatory bowel disease: recent advances.

作者信息

Honap Sailish, Agorogianni Alexandra, Colwill Michael J, Mehta Sonia Kalyanji, Donovan Fiona, Pollok Richard, Poullis Andrew, Patel Kamal

机构信息

Department of Gastroenterology and Hepatology, St George's University Hospitals NHS Foundation Trust, London, UK.

School of Immunology and Microbial Sciences, King's College, London, UK.

出版信息

Frontline Gastroenterol. 2023 Sep 14;15(1):59-69. doi: 10.1136/flgastro-2023-102400. eCollection 2024 Jan.

Abstract

Inflammatory bowel disease (IBD) commonly requires immunosuppressive treatments to induce and maintain durable remission. Janus kinase inhibitors (JAKis) are a novel group of orally administered, small molecule drugs that work by attenuating multiple cytokine signalling pathways to mediate dysregulated immune responses involved in the pathogenesis of IBD. Tofacitinib, filgotinib and upadacitinib have demonstrated efficacy against placebo and are licensed for the treatment of moderate to severe ulcerative colitis; upadacitinib is the only JAKi also currently approved for the treatment of Crohn's disease. Safety concerns stratified by age have led to class-wide regulatory restrictions for JAKi use across all inflammatory diseases. It is important for gastroenterologists managing patients with IBD to be aware of the key pivotal trial outcomes, to identify appropriate patients in whom to commence a JAKi, and to understand the safety considerations and ways to mitigate these risks in the patients they treat. This review provides a contemporaneous overview of this emerging therapeutic class and provides a practical guide for healthcare practitioners for initiating and monitoring JAKi in IBD.

摘要

炎症性肠病(IBD)通常需要免疫抑制治疗来诱导并维持持久缓解。Janus激酶抑制剂(JAKi)是一类新型口服小分子药物,其作用机制是通过减弱多种细胞因子信号通路,来调节IBD发病机制中失调的免疫反应。托法替布、非戈替尼和乌帕替尼已证明对安慰剂有效,并被批准用于治疗中度至重度溃疡性结肠炎;乌帕替尼是目前唯一也被批准用于治疗克罗恩病的JAKi。按年龄分层的安全性问题导致在所有炎症性疾病中对JAKi的使用都进行了全类别监管限制。对于管理IBD患者的胃肠病学家来说,了解关键的关键试验结果、确定开始使用JAKi的合适患者,并了解他们所治疗患者的安全注意事项以及降低这些风险的方法非常重要。本综述对这一新兴治疗类别进行了同步概述,并为医疗从业者在IBD中启动和监测JAKi提供了实用指南。

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