乌帕替尼维持治疗中度至重度活动性克罗恩病患者的疗效和安全性：U-ENDURE长期扩展研究的2年结果

Efficacy and Safety of Upadacitinib Maintenance Therapy in Patients with Moderately to Severely Active Crohn's Disease: 2-Year Results from the U-ENDURE Long-Term Extension Study.

作者信息

Loftus Edward V, D'Haens Geert, Louis Edouard, Regueiro Miguel, Jairath Vipul, Magro Fernando, Nakase Hiroshi, Dubcenco Elena, Lacerda Ana Paula, Ford Sharanya, Feng Tian, Duncan Benjamin, Fish Irina, Cunneen Colla, Anyanwu Samuel I, Aponte Fernando, Griffith Jenny, Blumenstein Irina

机构信息

Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.

Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Amsterdam, The Netherlands.

出版信息

J Crohns Colitis. 2025 Jul 24. doi: 10.1093/ecco-jcc/jjaf138.

DOI:10.1093/ecco-jcc/jjaf138

PMID:40704669

Abstract

BACKGROUND AND AIMS

The long-term efficacy and safety of upadacitinib in patients with moderate to severe Crohn's disease (CD) were evaluated in the U-ENDURE long-term extension (LTE) study. Here we report the results after 2 years of total maintenance treatment.

METHODS

U-ENDURE is an ongoing 240-week LTE study conducted at 243 sites across in 43 countries (first patient enrolled in LTE 21 March 2019). Patients who completed the 52-week maintenance study continued their previously assigned treatment, once-daily upadacitinib 15 mg or upadacitinib 30 mg. Efficacy and safety were assessed through LTE week 48 for patients in the 52-maintenance study and LTE study (cumulative maintenance population) and the LTE study only (cutoff date: 19 December 2023).

RESULTS

From LTE week 0 to week 48, as-observed efficacy rates for clinical remission (per stool frequency/abdominal pain score, upadacitinib 15 mg: 78.3% to 82.9%; upadacitinib 30 mg: 84.7% to 76.6%; per CD Activity Index, upadacitinib 15 mg: 81.3% to 83.1%; upadacitinib 30 mg: 86.1% to 86.8%), endoscopic response (upadacitinib 15 mg: 59.6% to 67.1%; upadacitinib 30 mg: 71.2% to 69.6%), inflammatory biomarkers, and quality-of-life outcomes remained stable. The safety profile of the cumulative maintenance population observed through LTE week 48 was consistent with previous trials in the upadacitinib CD program. Treatment-emergent adverse event rates for the cumulative maintenance population were 283.1 and 273.4 events/100 patient-years for upadacitinib 15 mg and upadacitinib 30 mg, respectively. Event rates of serious treatment-emergent adverse events were 16.0 events/100 patient-years for upadacitinib 15 mg and 14.6 events/100 patient-years for upadacitinib 30 mg. The most common adverse events of special interest (≥ 5.0 events/100 patient-years) were hepatic disorder, lymphopenia, creatine phosphokinase elevation, herpes zoster, and anemia. There was 1 treatment-emergent adverse event of suicide leading to death.

CONCLUSION

Sustained clinical, endoscopic, quality-of-life, and biomarker outcomes were observed in patients who were initial responders to upadacitinib and completed 2 years of maintenance therapy, with no new safety signals identified.

CLINICAL TRIAL IDENTIFIER

U-ENDURE; ClinicalTrials.gov number, NCT03345823.

摘要

背景与目的

在U-ENDURE长期扩展（LTE）研究中评估了乌帕替尼治疗中度至重度克罗恩病（CD）患者的长期疗效和安全性。在此，我们报告2年全疗程维持治疗后的结果。

方法

U-ENDURE是一项正在进行的为期240周的LTE研究，在43个国家的243个地点开展（首例患者于2019年3月21日纳入LTE研究）。完成52周维持治疗研究的患者继续接受之前分配的治疗，即每日一次口服15mg乌帕替尼或30mg乌帕替尼。对52周维持治疗研究和LTE研究（累积维持治疗人群）中的患者以及仅LTE研究中的患者（截止日期：2023年12月19日）进行至LTE第48周的疗效和安全性评估。

结果

从LTE第0周到第48周，观察到的临床缓解有效率（根据大便频率/腹痛评分，15mg乌帕替尼：78.3%至82.9%；30mg乌帕替尼：84.7%至76.6%；根据CD活动指数，15mg乌帕替尼：81.3%至83.1%；30mg乌帕替尼：86.1%至86.8%）、内镜反应（15mg乌帕替尼：59.6%至67.1%；30mg乌帕替尼：71.2%至69.6%）、炎症生物标志物以及生活质量结果均保持稳定。通过LTE第48周观察到的累积维持治疗人群的安全性特征与乌帕替尼CD项目之前的试验一致。累积维持治疗人群中，15mg乌帕替尼和30mg乌帕替尼的治疗中出现的不良事件发生率分别为283.1和273.4事件/100患者年。严重治疗中出现的不良事件发生率，15mg乌帕替尼为16.0事件/100患者年，30mg乌帕替尼为14.6事件/100患者年。特别关注的最常见不良事件（≥5.0事件/100患者年）为肝脏疾病、淋巴细胞减少、肌酸磷酸激酶升高、带状疱疹和贫血。有1例治疗中出现的自杀不良事件导致死亡。