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小分子,大成效:JAK抑制剂如何改变炎症性肠病患者的治疗方式

Small Molecules, Big Results: How JAK Inhibitors Have Transformed the Treatment of Patients with IBD.

作者信息

Fansiwala Kush, Sauk Jenny S

机构信息

Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

出版信息

Dig Dis Sci. 2025 Feb;70(2):469-477. doi: 10.1007/s10620-024-08792-0. Epub 2024 Dec 20.

Abstract

Small molecule Janus kinase (JAK) inhibitors have revolutionized the management of ulcerative colitis (UC) and Crohn's disease (CD) through their low immunogenicity, safety, and consistent pharmacologic response that are superior to existing therapeutic options. In this perspective, we highlight existing evidence supporting the use of currently approved JAK inhibitors (upadacitinib, tofacitinib, and filgotinib) for UC or CD, additionally emphasizing the evidence for their use in related autoimmune conditions such as rheumatoid arthritis and spondyloarthropathies. Our perspective concludes with a review of the existing comparative effectiveness literature, which positions JAK inhibitors, particularly upadacitinib, favorably compared with other biologic therapies. This perspective is paired with a companion publication highlighting the origins and development of JAK inhibitors and a more in-depth review of their pathophysiologic mechanisms.

摘要

小分子 Janus 激酶(JAK)抑制剂凭借其低免疫原性、安全性以及优于现有治疗方案的一致药理反应,彻底改变了溃疡性结肠炎(UC)和克罗恩病(CD)的治疗方式。从这一角度出发,我们着重介绍支持目前已获批的 JAK 抑制剂(乌帕替尼、托法替布和非戈替尼)用于 UC 或 CD 的现有证据,此外还强调了它们用于类风湿关节炎和脊柱关节病等相关自身免疫性疾病的证据。我们的观点以对现有比较疗效文献的综述作为结尾,该综述表明 JAK 抑制剂,尤其是乌帕替尼,与其他生物疗法相比具有优势。此观点与一篇配套出版物相关联,该出版物着重介绍了 JAK 抑制剂的起源与发展,并对其病理生理机制进行了更深入的综述。

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