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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?所有用于治疗炎症性肠病的Janus激酶抑制剂都一样吗?
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3
The evolving role of JAK inhibitors in the treatment of inflammatory bowel disease.JAK 抑制剂在炎症性肠病治疗中的不断演变的角色。
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.用于维持溃疡性结肠炎缓解的口服 Janus 激酶抑制剂
Cochrane Database Syst Rev. 2020 Jan 27;1(1):CD012381. doi: 10.1002/14651858.CD012381.pub2.
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JAK Inhibitors Safety in Ulcerative Colitis: Practical Implications.JAK抑制剂在溃疡性结肠炎中的安全性:实际意义
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Therapeutic potential of Janus kinase inhibitors for the management of fibrosis in inflammatory bowel disease.Janus激酶抑制剂在炎症性肠病纤维化管理中的治疗潜力。
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本文引用的文献

1
Efficacy and Safety Outcomes Up to ~4 Years of Treatment With Filgotinib 200 mg Among Patients With Ulcerative Colitis: Results From the SELECTIONLTE Study.溃疡性结肠炎患者使用200mg非戈替尼治疗长达约4年的疗效和安全性结果:SELECTION LTE研究结果
Gastroenterol Hepatol (N Y). 2023 Apr;19(4 Suppl 1):10-11.
2
Tofacitinib concentrations in plasma and breastmilk of a lactating woman with ulcerative colitis.一名患有溃疡性结肠炎的哺乳期妇女血浆和母乳中的托法替布浓度。
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.JAK 抑制剂与恶性肿瘤风险:疾病适应证的荟萃分析。
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.乌帕替尼诱导缓解和维持治疗克罗恩病。
N Engl J Med. 2023 May 25;388(21):1966-1980. doi: 10.1056/NEJMoa2212728.
5
Effects of filgotinib on semen parameters and sex hormones in male patients with inflammatory diseases: results from the phase 2, randomised, double-blind, placebo-controlled MANTA and MANTA-RAy studies.在炎症性疾病男性患者中,Filgotinib 对精液参数和性激素的影响:来自 2 期、随机、双盲、安慰剂对照的 MANTA 和 MANTA-RAy 研究结果。
Ann Rheum Dis. 2023 Aug;82(8):1049-1058. doi: 10.1136/ard-2023-224017. Epub 2023 May 3.
6
Filgotinib for the Treatment of Small Bowel Crohn's Disease: The DIVERGENCE 1 Trial.非戈替尼治疗小肠克罗恩病:DIVERGENCE 1试验
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.综述文章:接受小分子药物治疗的炎症性肠病患者发生心血管事件的风险。
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.JAK抑制剂:炎症性肠病口服疗法的新曙光。
Front Med (Lausanne). 2023 Mar 2;10:1089099. doi: 10.3389/fmed.2023.1089099. eCollection 2023.
9
Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis.在类风湿关节炎、银屑病关节炎、强直性脊柱炎和特应性皮炎中,乌帕替尼的安全性数据超过 15000 患者-年。
RMD Open. 2023 Feb;9(1). doi: 10.1136/rmdopen-2022-002735.
10
Malignancy risk with tofacitinib versus TNF inhibitors in rheumatoid arthritis: results from the open-label, randomised controlled ORAL Surveillance trial.托法替布与肿瘤坏死因子抑制剂治疗类风湿关节炎的恶性肿瘤风险:来自开放标签、随机对照 ORAL Surveillance 试验的结果。
Ann Rheum Dis. 2023 Mar;82(3):331-343. doi: 10.1136/ard-2022-222543. Epub 2022 Dec 5.

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.

DOI:10.1136/flgastro-2023-102400
PMID:38487554
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10935522/
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。