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酪氨酸激酶 2 抑制剂在自身免疫性疾病中的应用。

Tyrosine kinase 2 inhibitors in autoimmune diseases.

机构信息

Department of Rheumatology, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton SO16 6YD, UK.

Department of Rheumatology, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton SO16 6YD, UK.

出版信息

Autoimmun Rev. 2024 Nov;23(11):103649. doi: 10.1016/j.autrev.2024.103649. Epub 2024 Sep 29.

DOI:10.1016/j.autrev.2024.103649
PMID:39349269
Abstract

Tyk2 is a member of the JAK kinase family. It is an important mediator in pro-inflammatory signalling, implicated in both innate and adaptive immune system. Activation of Tyk2 is believed to be integral to cellular processes that contribute to the development and progression of autoimmune disorders. Selective targeting of Tyk2 may reduce the number of adverse events as compared to non-selective JAK inhibitors. Therefore, in recent years there has been a growing body of research examining the inhibition of Tyk2 as a therapeutic intervention in autoimmune disease. Deucravacitinib has been approved for the treatment of moderate to severe skin psoriasis. This drug and other novel Tyk2 inhibitors are now being explored as therapies for multiple autoimmune diseases, including psoriatic arthritis, SLE, Sjogren's, dermatomyositis, inflammatory bowel disease, uveitis, hidradenitis suppurativa and others. Tyk2 inhibitors offer a potentially exciting new treatment option across a wide range of autoimmune diseases. We discuss Tyk2 inhibition, the current evidence for its usage to date, ongoing trials and what the future might hold.

摘要

TYK2 是 JAK 激酶家族的一员。它是促炎信号的重要介质,参与固有和适应性免疫系统。TYK2 的激活被认为是对有助于自身免疫性疾病发展和进展的细胞过程至关重要的。与非选择性 JAK 抑制剂相比,选择性靶向 TYK2 可能会减少不良事件的发生。因此,近年来越来越多的研究探讨了 TYK2 抑制作为自身免疫性疾病治疗干预的作用。德瓦鲁单抗已被批准用于治疗中度至重度皮肤银屑病。这种药物和其他新型 TYK2 抑制剂目前正在作为多种自身免疫性疾病的治疗方法进行探索,包括银屑病关节炎、系统性红斑狼疮、干燥综合征、皮肌炎、炎症性肠病、葡萄膜炎、化脓性汗腺炎等。TYK2 抑制剂为广泛的自身免疫性疾病提供了一种潜在令人兴奋的新治疗选择。我们讨论了 TYK2 抑制,迄今为止其使用的现有证据,正在进行的试验以及未来可能的发展方向。

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