接受埃曲莫德治疗的溃疡性结肠炎患者的内镜、组织学及综合终点指标

Endoscopic, Histologic, and Composite Endpoints in Patients With Ulcerative Colitis Treated With Etrasimod.

作者信息

Magro Fernando, Peyrin-Biroulet Laurent, Sands Bruce E, Danese Silvio, Jairath Vipul, Goetsch Martina, Bhattacharjee Abhishek, Wu Joseph, Branquinho Diogo, Modesto Irene, Feagan Brian G

机构信息

CINTESIS@RISE, Faculty of Medicine, University of Porto, Porto, Portugal.

Department of Gastroenterology, Nancy University Hospital, Vandœuvre-lès-Nancy, France; INSERM, NGERE, University of Lorraine, Nancy, France; INFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy, France; FHU-CURE, Nancy University Hospital, Vandœuvre-lès-Nancy, France; Groupe Hospitalier privé Ambroise Paré - Hartmann, Paris IBD Center, Neuilly-sur-Seine, France; Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada.

出版信息

Clin Gastroenterol Hepatol. 2025 Feb;23(2):341-350.e6. doi: 10.1016/j.cgh.2024.07.010. Epub 2024 Jul 31.

DOI:10.1016/j.cgh.2024.07.010

PMID:39089519

Abstract

BACKGROUND & AIMS: Histologic remission, a potentially important treatment target in ulcerative colitis (UC), is associated with favorable long-term outcomes. Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P) receptor modulator for the treatment of moderately to severely active UC. This post-hoc analysis of the ELEVATE UC program evaluated the efficacy of etrasimod according to histologic and composite (histologic/endoscopic/symptomatic) endpoints and examined their prognostic value.

METHODS

Patients with moderately to severely active UC were randomized 2:1 to once-daily oral etrasimod 2 mg or placebo. Histologic and composite endpoints, including disease clearance (endoscopic/histologic/symptomatic remission), were assessed at Weeks 12 (ELEVATE UC 52; ELEVATE UC 12) and 52 (ELEVATE UC 52). Logistic regressions examined associations between baseline and Week 12 histologic/composite endpoints and Week 52 outcomes.

RESULTS

At Weeks 12 and 52, significant improvements with etrasimod vs placebo were observed in histologic/composite outcomes, including endoscopic improvement-histologic remission and disease clearance. The proportion of patients treated with etrasimod achieving clinical remission at Week 52 was higher among those with disease clearance at Week 12 vs those without disease clearance (73.9% [17/23] vs 28.3% [71/251]). Histologic improvement and endoscopic improvement at Week 12 were moderately and strongly associated with clinical remission at Week 52 (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.27-4.41; and OR, 6.36; 95% CI, 3.47-11.64, respectively). Histologic remission and endoscopic improvement at Week 12 were strongly associated with endoscopic improvement-histologic remission at Week 52 (OR, 3.21; 95% CI, 1.70-6.06 and OR, 5.47; 95% CI, 2.89-10.36, respectively).

CONCLUSIONS

Etrasimod was superior to placebo for achievement of stringent histologic and composite endpoints.

CLINICALTRIALS

gov, Number: NCT03945188; ClinicalTrials.gov, Number: NCT03996369.

摘要

背景与目的

组织学缓解是溃疡性结肠炎（UC）潜在的重要治疗目标，与良好的长期预后相关。埃特拉莫德是一种口服、每日一次的选择性1-磷酸鞘氨醇（S1P）受体调节剂，用于治疗中度至重度活动性UC。这项对ELEVATE UC项目的事后分析根据组织学和综合（组织学/内镜/症状）终点评估了埃特拉莫德的疗效，并研究了它们的预后价值。

方法

中度至重度活动性UC患者按2:1随机分为每日一次口服2 mg埃特拉莫德或安慰剂组。在第12周（ELEVATE UC 52；ELEVATE UC 12）和第52周（ELEVATE UC 52）评估组织学和综合终点，包括疾病清除（内镜/组织学/症状缓解）。逻辑回归分析了基线和第12周组织学/综合终点与第52周结局之间的关联。

结果

在第12周和第52周，与安慰剂相比，埃特拉莫德在组织学/综合结局方面有显著改善,包括内镜改善-组织学缓解和疾病清除。在第12周达到疾病清除的患者中，接受埃特拉莫德治疗在第52周实现临床缓解的患者比例高于未达到疾病清除的患者（73.9% [17/23] 对28.3% [71/251]）。第12周的组织学改善和内镜改善与第52周的临床缓解呈中度和强关联（优势比 [OR]，2.37；95% 置信区间 [CI]，1.27 - 4.41；以及OR，6.36；95% CI，3.47 - 11.64）。第12周的组织学缓解和内镜改善与第52周的内镜改善-组织学缓解呈强关联（OR，3.21；95% CI，1.70 - 6.06和OR，5.47；95% CI，2.89 - 10.36）。