Suppr超能文献

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。

相似文献

1
JAK inhibitors for inflammatory bowel disease: recent advances.
Frontline Gastroenterol. 2023 Sep 14;15(1):59-69. doi: 10.1136/flgastro-2023-102400. eCollection 2024 Jan.
2
Are All Janus Kinase Inhibitors for Inflammatory Bowel Disease the Same?
Gastroenterol Hepatol (N Y). 2023 Dec;19(12):727-738.
3
The evolving role of JAK inhibitors in the treatment of inflammatory bowel disease.
Expert Rev Clin Immunol. 2023 Jul-Dec;19(9):1075-1089. doi: 10.1080/1744666X.2023.2214728. Epub 2023 May 24.
4
Oral Janus kinase inhibitors for maintenance of remission in ulcerative colitis.
Cochrane Database Syst Rev. 2020 Jan 27;1(1):CD012381. doi: 10.1002/14651858.CD012381.pub2.
5
JAK Inhibitors Safety in Ulcerative Colitis: Practical Implications.
J Crohns Colitis. 2020 Aug 1;14(Supplement_2):S755-S760. doi: 10.1093/ecco-jcc/jjaa017.
6
User's guide to JAK inhibitors in inflammatory bowel disease.
Curr Res Pharmacol Drug Discov. 2022 Mar 3;3:100096. doi: 10.1016/j.crphar.2022.100096. eCollection 2022.
9
JAK inhibitors: A new dawn for oral therapies in inflammatory bowel diseases.
Front Med (Lausanne). 2023 Mar 2;10:1089099. doi: 10.3389/fmed.2023.1089099. eCollection 2023.
10
Pharmacology, efficacy and safety of JAK inhibitors in Crohn's disease.
Best Pract Res Clin Gastroenterol. 2019 Feb-Apr;38-39:101606. doi: 10.1016/j.bpg.2019.03.002. Epub 2019 Mar 6.

引用本文的文献

1
Autoimmune Hemolytic Anemia From Tofacitinib Use in a Patient With Ulcerative Colitis.
ACG Case Rep J. 2024 Sep 27;11(10):e01528. doi: 10.14309/crj.0000000000001528. eCollection 2024 Oct.
4
Ulcerative colitis: Timeline to a cure.
World J Gastroenterol. 2025 Jul 14;31(26):108375. doi: 10.3748/wjg.v31.i26.108375.
6
A Review of the Current State of Off-Label Therapies for Pediatric Inflammatory Bowel Disease.
Pediatr Discov. 2025 Jun 17;3(2):e70011. doi: 10.1002/pdi3.70011. eCollection 2025 Jun.
7
Etrasimod in Treatment of Ulcerative Colitis: A Comprehensive Review.
Turk J Gastroenterol. 2025 Jun 2;36(6):336-342. doi: 10.5152/tjg.2025.25148.
10
NDP52 and its emerging role in pathogenesis.
Cell Death Dis. 2025 May 3;16(1):359. doi: 10.1038/s41419-025-07668-z.

本文引用的文献

2
Tofacitinib concentrations in plasma and breastmilk of a lactating woman with ulcerative colitis.
Lancet Gastroenterol Hepatol. 2023 Aug;8(8):695-697. doi: 10.1016/S2468-1253(23)00158-9. Epub 2023 Jun 1.
3
JAK inhibitors and the risk of malignancy: a meta-analysis across disease indications.
Ann Rheum Dis. 2023 Aug;82(8):1059-1067. doi: 10.1136/ard-2023-224049. Epub 2023 May 29.
4
Upadacitinib Induction and Maintenance Therapy for Crohn's Disease.
N Engl J Med. 2023 May 25;388(21):1966-1980. doi: 10.1056/NEJMoa2212728.
6
Filgotinib for the Treatment of Small Bowel Crohn's Disease: The DIVERGENCE 1 Trial.
Gastroenterology. 2023 Jul;165(1):289-292.e3. doi: 10.1053/j.gastro.2023.03.234. Epub 2023 Apr 11.
7
Review article: Risk of cardiovascular events in patients with inflammatory bowel disease receiving small molecule drugs.
Aliment Pharmacol Ther. 2023 Jun;57(11):1231-1248. doi: 10.1111/apt.17509. Epub 2023 Apr 10.
8
JAK inhibitors: A new dawn for oral therapies in inflammatory bowel diseases.
Front Med (Lausanne). 2023 Mar 2;10:1089099. doi: 10.3389/fmed.2023.1089099. eCollection 2023.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验