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炎症性肠病中 Janus 激酶拮抗剂的最新进展

Update on Janus kinase antagonists in inflammatory bowel disease.

作者信息

Boland Brigid S, Sandborn William J, Chang John T

机构信息

Division of Gastroenterology, Department of Medicine, Inflammatory Bowel Disease Center, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Digestive Diseases Research Development Center, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.

Division of Gastroenterology, Department of Medicine, Inflammatory Bowel Disease Center, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Digestive Diseases Research Development Center, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.

出版信息

Gastroenterol Clin North Am. 2014 Sep;43(3):603-17. doi: 10.1016/j.gtc.2014.05.011. Epub 2014 Jun 24.

DOI:10.1016/j.gtc.2014.05.011
PMID:25110261
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4129380/
Abstract

Janus kinase (JAK) inhibitors have emerged as a novel orally administered small-molecule therapy for the treatment of ulcerative colitis and possibly Crohn disease. These molecules are designed to selectively target the activity of specific JAKs and to offer a targeted mechanism of action without risk of immunogenicity. Based on data from clinical trials in rheumatoid arthritis and phase 2 studies in inflammatory bowel disease, tofacitinib and other JAK inhibitors are likely to become a new form of medical therapy for the treatment of inflammatory bowel disease.

摘要

Janus激酶(JAK)抑制剂已成为一种新型的口服小分子疗法,用于治疗溃疡性结肠炎,也可能用于治疗克罗恩病。这些分子旨在选择性地靶向特定JAK的活性,并提供一种靶向作用机制,而没有免疫原性风险。基于类风湿关节炎的临床试验数据和炎症性肠病的2期研究,托法替布和其他JAK抑制剂可能会成为治疗炎症性肠病的一种新的药物治疗形式。

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Update on Janus kinase antagonists in inflammatory bowel disease.炎症性肠病中 Janus 激酶拮抗剂的最新进展
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本文引用的文献

1
A randomized, double-blind, placebo-controlled, twelve-week, dose-ranging study of decernotinib, an oral selective JAK-3 inhibitor, as monotherapy in patients with active rheumatoid arthritis.一项随机、双盲、安慰剂对照、为期十二周、剂量范围的研究,评估了口服选择性 JAK-3 抑制剂地瑞努替尼(decerotinib)作为活性类风湿关节炎患者的单药治疗。
Arthritis Rheumatol. 2015 Feb;67(2):334-43. doi: 10.1002/art.38949.
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A phase 2 study of tofacitinib, an oral Janus kinase inhibitor, in patients with Crohn's disease.一项评估托法替布(一种口服 JAK 抑制剂)治疗克罗恩病患者的 2 期临床研究。
Clin Gastroenterol Hepatol. 2014 Sep;12(9):1485-93.e2. doi: 10.1016/j.cgh.2014.01.029. Epub 2014 Jan 27.
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乌帕替尼治疗溃疡性结肠炎患者的真实世界有效性和安全性:一项系统评价和荟萃分析
J Clin Med. 2025 Mar 25;14(7):2232. doi: 10.3390/jcm14072232.
4
Tofacitinib downregulates JAK1 and JAK3 on human intestinal monocytes and macrophages without affecting dendritic cells phenotype or function.托法替布可下调人肠道单核细胞和巨噬细胞上的JAK1和JAK3,而不影响树突状细胞的表型或功能。
J Transl Autoimmun. 2025 Jan 22;10:100271. doi: 10.1016/j.jtauto.2025.100271. eCollection 2025 Jun.
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Real-World Effectiveness and Safety of Selective JAK Inhibitors in Ulcerative Colitis and Crohn's Disease: A Retrospective, Multicentre Study.选择性JAK抑制剂在溃疡性结肠炎和克罗恩病中的真实世界有效性及安全性:一项回顾性多中心研究
J Clin Med. 2024 Dec 20;13(24):7804. doi: 10.3390/jcm13247804.
6
Linoleyl acetate and mandenol alleviate HUA-induced ED via NLRP3 inflammasome and JAK2/STAT3 signalling conduction in rats.乙酸亚油酸酯和芒柄醇通过 NLRP3 炎性小体和 JAK2/STAT3 信号传导缓解 HUA 诱导的 ED 大鼠模型。
J Cell Mol Med. 2024 Sep;28(17):e70075. doi: 10.1111/jcmm.70075.
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Safety and effectiveness of tofacitinib in Korean adult patients with ulcerative colitis: post-marketing surveillance study.托法替布治疗韩国成年溃疡性结肠炎患者的安全性和有效性:上市后监测研究。
BMC Gastroenterol. 2024 Aug 19;24(1):273. doi: 10.1186/s12876-024-03336-2.
8
Spondyloarthritis with inflammatory bowel disease: the latest on biologic and targeted therapies.脊柱关节炎合并炎症性肠病:生物制剂和靶向治疗的最新进展。
Nat Rev Rheumatol. 2023 Aug;19(8):503-518. doi: 10.1038/s41584-023-00984-8. Epub 2023 Jun 29.
9
Improvements in Disease Activity Partially Mediate the Effect of Tofacitinib Treatment on Generic and Disease-Specific Health-Related Quality of Life in Patients with Ulcerative Colitis: Data from the OCTAVE Program.托法替布治疗对溃疡性结肠炎患者一般健康相关和疾病特异性生活质量的影响部分通过疾病活动改善介导:OCTAVE 研究的数据。
Dig Dis. 2023;41(4):604-614. doi: 10.1159/000528788. Epub 2023 Jan 5.
10
Endo-histologic Normalization Is Achievable with Tofacitinib and Is Associated with Improved Clinical Outcomes.托法替布可实现组织学内正常化,并与改善的临床结果相关。
Dig Dis Sci. 2023 Apr;68(4):1464-1472. doi: 10.1007/s10620-022-07716-0. Epub 2022 Oct 15.
Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial.
托法替布联合非生物性疾病修正抗风湿药物治疗活动期类风湿关节炎患者的随机试验。
Ann Intern Med. 2013 Aug 20;159(4):253-61. doi: 10.7326/0003-4819-159-4-201308200-00006.
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The effectiveness of tofacitinib, a novel Janus kinase inhibitor, in the treatment of rheumatoid arthritis: a systematic review and meta-analysis.新型 Janus 激酶抑制剂托法替布治疗类风湿关节炎的有效性:系统评价和荟萃分析。
Clin Rheumatol. 2013 Oct;32(10):1415-24. doi: 10.1007/s10067-013-2329-9. Epub 2013 Jul 23.
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Janus kinase inhibitors in autoimmune diseases.自身免疫性疾病中的 Janus 激酶抑制剂。
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Open-label tofacitinib and double-blind atorvastatin in rheumatoid arthritis patients: a randomised study.开放标签托法替尼和双盲阿托伐他汀在类风湿关节炎患者中的应用:一项随机研究。
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Aliment Pharmacol Ther. 2013 Apr;37(8):786-94. doi: 10.1111/apt.12262. Epub 2013 Feb 21.
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JAKs and STATs in immunity, immunodeficiency, and cancer.免疫、免疫缺陷和癌症中的JAKs与STATs
N Engl J Med. 2013 Jan 10;368(2):161-70. doi: 10.1056/NEJMra1202117.
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Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.宿主-微生物相互作用塑造了炎症性肠病的遗传结构。
Nature. 2012 Nov 1;491(7422):119-24. doi: 10.1038/nature11582.
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Crohn's disease.克罗恩病。
Lancet. 2012 Nov 3;380(9853):1590-605. doi: 10.1016/S0140-6736(12)60026-9. Epub 2012 Aug 20.