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Evaluating tofacitinib citrate in the treatment of moderate-to-severe active ulcerative colitis: design development and positioning of therapy

机译:评估柠檬酸托法替尼在中度至重度活动性溃疡性结肠炎的治疗中:疗法的设计开发和定位

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摘要

The etiology of ulcerative colitis (UC) is complex and involves a host of genetic, epigenetic and environmental factors. Over the last thirty years, signaling pathways like the Janus kinase (JAK) signaling pathway have been implicated in its pathogenesis. Pharmacologic blockade of this pathway is available through several small molecule inhibitors, including tofacitinib. Tofacitinib is an orally administered pan-JAK inhibitor that was first approved by the Food and Drug Administration (FDA) for use in rheumatologic disorders such as rheumatoid arthritis and psoriatic arthritis. The FDA approved its use in moderate-to-severe active ulcerative colitis in 2018. The aim of this review will be to discuss the role of tofacitinib in ulcerative colitis. We will discuss the role of JAK-STAT signaling, clinical data available for tofacitinib, and the safety profile for this therapy. Tofacitinib’s place in the UC management algorithm is currently being debated. This effective oral therapy is poised to be a mainstay of UC therapeutics. This review will highlight the key clinical features and detail the UC experience to date.
机译:溃疡性结肠炎(UC)的病因复杂,涉及许多遗传,表观遗传和环境因素。在过去的三十年中,像Janus激酶(JAK)信号传导途径这样的信号传导途径已经涉及其发病机理。可通过几种小分子抑制剂(包括托法替尼)获得此途径的药理阻断作用。 Tofacitinib是一种口服的pan-JAK抑制剂,最初是由美国食品药品管理局(FDA)批准用于风湿性疾病(如类风湿性关节炎和银屑病关节炎)的。 FDA于2018年批准了其在中度至重度活动性溃疡性结肠炎中的应用。本综述的目的是讨论托法替尼在溃疡性结肠炎中的作用。我们将讨论JAK-STAT信号传导的作用,托法替尼可用的临床数据以及该疗法的安全性。托法替尼在UC管理算法中的位置目前正在辩论中。这种有效的口服治疗有望成为UC治疗的主要手段。这篇综述将重点介绍关键的临床特征,并详细介绍迄今为止的UC经验。

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