乌帕替尼用于克罗恩病的维持治疗：3期随机U-ENDURE研究的最终结果
Upadacitinib Maintenance Therapy in Crohn's Disease: Final Results From the Randomized Phase 3 U-ENDURE Study.
作者信息
Panaccione Remo, Regueiro Miguel, Lee Scott D, Atreya Raja, Pedersen Gitte, Broide Efrat, Rodriguez Cristina, van Bodegraven Adriaan A, Dubcenco Elena, Lacerda Ana P, Feng Tian, Geng Ziqian, Wang Tao, van Haaren Stijn, Anyanwu Samuel I, Panés Julian
机构信息
Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada.
Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, Ohio.
出版信息
Clin Gastroenterol Hepatol. 2025 Jul 28. doi: 10.1016/j.cgh.2025.07.028.
BACKGROUND & AIMS: Upadacitinib, an oral, reversible Janus kinase inhibitor, demonstrated efficacy and safety in patients with Crohn's disease in 2 phase III induction trials (U-EXCEL and U-EXCEED) and in a primary analysis of the first 502 patients entering the subsequent maintenance trial (U-ENDURE). Here, we present the overall results of the entire population of U-ENDURE (N = 673).
METHODS
Clinical responders to 12 weeks of upadacitinib 45 mg once daily (QD) induction were randomized (1:1:1) to receive upadacitinib 15 mg QD (n = 221), upadacitinib 30 mg QD (n = 229), or placebo (n = 223) as maintenance therapy for 52 weeks. Coprimary endpoints were Crohn's Disease Activity Index (CDAI) clinical remission and endoscopic response at week 52. Safety was assessed through week 52.
RESULTS
At week 52, more upadacitinib-treated vs placebo patients achieved CDAI clinical remission (upadacitinib 15 mg, 36.2% and upadacitinib 30 mg, 51.5% vs placebo, 15.2%). The rates of endoscopic response were 27.3% for upadacitinib 15 mg and 40.7% for upadacitinib 30 mg vs 7.2% for placebo. Exposure-adjusted event rates for treatment-emergent adverse events were numerically lower with upadacitinib 15 mg and 30 mg vs placebo (351.3 and 324.5 per 100 patient-years, respectively, vs 462.8 per 100 patient-years) except for COVID-19 and adverse events leading to early discontinuation of study treatment. No deaths, active tuberculosis, lymphoma, nonmelanoma skin cancer, adjudicated major cardiovascular adverse events, or venous thromboembolic events were reported from any treatment group. Herpes zoster infections occurred more frequently in the upadacitinib groups compared with placebo; all were nonserious, and most involved a single dermatome.
CONCLUSION
Consistent with the primary analysis, upadacitinib was more efficacious than placebo in achieving clinical and endoscopic endpoints in patients with Crohn's disease. The safety profile remained consistent with no new safety signals.
CLINICALTRIALS
gov Number: NCT03345823.
背景与目的
乌帕替尼是一种口服可逆性 Janus 激酶抑制剂，在两项 III 期诱导试验（U-EXCEL 和 U-EXCEED）以及对进入后续维持试验（U-ENDURE）的首批 502 例患者的初步分析中，已证明其对克罗恩病患者具有疗效和安全性。在此，我们展示了 U-ENDURE 全部患者群体（N = 673）的总体结果。
方法
对每日一次口服 45 mg 乌帕替尼诱导治疗 12 周的临床缓解者进行随机分组（1:1:1），分别接受 15 mg 每日一次的乌帕替尼（n = 221）、30 mg 每日一次的乌帕替尼（n = 229）或安慰剂（n = 223）作为维持治疗，为期 52 周。共同主要终点为第 52 周时的克罗恩病活动指数（CDAI）临床缓解和内镜反应。对安全性的评估持续至第 52 周。
结果
在第 52 周时，接受乌帕替尼治疗的患者比接受安慰剂治疗的患者实现 CDAI 临床缓解的更多（15 mg 乌帕替尼组为 36.2%，30 mg 乌帕替尼组为 51.5%，而安慰剂组为 15.2%）。15 mg 乌帕替尼组的内镜反应率为 27.3%，30 mg 乌帕替尼组为 40.7%，而安慰剂组为 7.2%。15 mg 和 30 mg 乌帕替尼治疗出现的不良事件的暴露调整事件率在数值上低于安慰剂（分别为每 100 患者年 351.3 和 324.5，而安慰剂为每 100 患者年 462.8），但不包括 COVID-19 和导致提前终止研究治疗的不良事件。各治疗组均未报告死亡、活动性结核病、淋巴瘤、非黑色素瘤皮肤癌、判定的主要心血管不良事件或静脉血栓栓塞事件。与安慰剂组相比，乌帕替尼组带状疱疹感染的发生频率更高；所有感染均不严重，且大多数累及单个皮节。
结论
与初步分析一致，在实现克罗恩病患者的临床和内镜终点方面，乌帕替尼比安慰剂更有效。安全性概况保持一致，未出现新的安全信号。
临床试验
美国国立医学图书馆临床试验注册中心编号：NCT03345823 。
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