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炎症性肠病中JAK抑制剂用户指南

User's guide to JAK inhibitors in inflammatory bowel disease.

作者信息

Spiewak Ted A, Patel Anish

机构信息

Division of Gastroenterology & Hepatology, Brooke Army Medical Center, USA.

出版信息

Curr Res Pharmacol Drug Discov. 2022 Mar 3;3:100096. doi: 10.1016/j.crphar.2022.100096. eCollection 2022.

Abstract

Inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn's disease (CD), are remitting and relapsing disorders of the gastrointestinal tract, highlighted by the dysregulation of pro- and anti-inflammatory mediators, which lead to mucosal damage. These conditions cause a significant burden worldwide as primary and secondary treatment failure rates remain high even with our current therapeutic options. This emphasizes the need for continued advancement in treatment efficacy with improved safety profiles. Novel disease-targeting therapeutics have been developed, most recently being the Janus kinase inhibitors (JAKi). JAKi serve as a promising new class of non-immunogenic small molecule inhibitors that modulate inflammatory pathways by blocking the critical role that Janus kinase (JAK) proteins play in mediating the innate and adaptive immune responses. Tofacitinib has been shown to be therapeutically efficacious, to have a tolerable safety profile, and to be available for adult patients with moderate-to-severe UC. This review was designed to serve as an overview and as practical guidance for medical practitioners. Author recommendations and appraisals of the quality of evidence throughout this article are based solely on personal opinion and are not the outcome of a formal methodology followed by a consensus group.

摘要

炎症性肠病(IBD),如溃疡性结肠炎(UC)和克罗恩病(CD),是胃肠道的缓解和复发型疾病,其特征为促炎和抗炎介质失调,进而导致黏膜损伤。这些疾病在全球造成了沉重负担,因为即便有当前的治疗选择,一线和二线治疗的失败率仍然很高。这凸显了在提高安全性的同时持续提升治疗效果的必要性。已开发出新型的疾病靶向疗法,最近的是 Janus 激酶抑制剂(JAKi)。JAKi 是一类有前景的非免疫原性小分子抑制剂,通过阻断 Janus 激酶(JAK)蛋白在介导先天性和适应性免疫反应中所起的关键作用来调节炎症途径。托法替布已被证明具有治疗效果、安全性可耐受,并且可供中重度 UC 的成年患者使用。本综述旨在为医学从业者提供概述和实用指南。本文作者的推荐以及对证据质量的评估完全基于个人观点,并非遵循共识小组的正式方法得出的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a561/8920857/82c94e69a897/ga1.jpg

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