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乌帕替尼在中度至重度活动性溃疡性结肠炎成年患者治疗中作用的最新进展。

Update on the role of upadacitinib in the treatment of adults with moderately to severely active ulcerative colitis.

作者信息

Ernest-Suarez Kenneth, Panaccione Remo

机构信息

Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, AB, Canada.

Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Rm 6D32, Cal Wenzel Precision Health Building, 3280 Hospital Dr NW, Calgary, AB T2N 4Z6, Canada.

出版信息

Therap Adv Gastroenterol. 2023 Mar 11;16:17562848231158235. doi: 10.1177/17562848231158235. eCollection 2023.

Abstract

With further knowledge of the pathogenesis of inflammatory bowel disease, small oral molecules have become available, including the Janus kinase (JAK) inhibitors. Upadacitinib (UPA) is a selective JAK1 inhibitor and has become the newest drug in this class, with recent approval for the management of moderate-to-severe ulcerative colitis. The large phase III program (including the U-ACHIEVE and U-ACCOMPLISH parallel induction trials and the U-ACHIEVE Maintenance trial) demonstrated superiority over placebo, for all primary and secondary endpoints including key clinical, endoscopic, and histological outcomes utilizing 45 mg orally (po) once daily (OD) during induction and either 30 mg or 15 mg po OD in maintenance. From a safety perspective, UPA has proven to be a safe and well-tolerated medication across immune-mediated diseases with manageable adverse risks such as an increase in herpes zoster. Proper discussion and patient profiling are essential when positioning UPA, considering efficacy and potential risks associated with this highly effective medication.

摘要

随着对炎症性肠病发病机制的进一步了解,一些口服小分子药物已可供使用,包括Janus激酶(JAK)抑制剂。乌帕替尼(UPA)是一种选择性JAK1抑制剂,已成为该类药物中的最新药物,最近被批准用于治疗中重度溃疡性结肠炎。大型III期试验项目(包括U-ACHIEVE和U-ACCOMPLISH平行诱导试验以及U-ACHIEVE维持试验)表明,在所有主要和次要终点方面,包括关键的临床、内镜和组织学结果,均优于安慰剂,诱导期采用每日一次口服45毫克(mg),维持期采用每日一次口服30毫克或15毫克。从安全性角度来看,在免疫介导疾病中,UPA已被证明是一种安全且耐受性良好的药物,其不良风险可控,如带状疱疹发病率增加。在定位UPA时,考虑到这种高效药物的疗效和潜在风险,进行适当的讨论和患者评估至关重要。

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