The efficacy and safety of etrasimod as a first-line advanced therapy for ulcerative colitis: prespecified and post hoc subgroup data from the ELEVATE UC clinical program.

IF 3.8 3区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Therapeutic Advances in Gastroenterology Pub Date : 2026-07-27 eCollection Date: 2026-01-01 DOI:10.1177/17562848261470909

David T Rubin, Charlie W Lees, Filip Baert, Maria Kudela, Abhishek Bhattacharjee, Krisztina Lazin, Martina Goetsch, Arcangelo M Abbatemarco, Karolina Wosik, John K Marshall

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引用次数: 0

Abstract

Background: Many patients show inadequate response or intolerance to conventional therapies for ulcerative colitis (UC), including 5-aminosalicylates (5-ASA), thiopurines, and corticosteroids (CS). Etrasimod is an oral, once daily (QD), selective sphingosine 1-phosphate (S1P) receptor modulator for the treatment of UC.

Objectives: We assessed efficacy and safety as a first-line advanced therapy following different scenarios of conventional treatment.

Design: In the phase III, multicenter, double-blind, placebo-controlled ELEVATE UC trials, eligible patients were randomized 2:1 to etrasimod 2 mg QD or placebo.

Methods: Subgroups of patients post-5-ASA failure (prespecified), post-5-ASA/CS (post hoc), and post-thiopurine/5-ASA/CS (post hoc) were assessed for clinical, endoscopic, and histologic endpoints. Safety was assessed throughout the trials.

Results: In ELEVATE UC 52, 74 patients (45 receiving etrasimod 2 mg QD and 29 receiving placebo) had prior failure of 5-ASA only. Among these patients, a greater proportion of those treated with etrasimod versus placebo met clinical, endoscopic, and histologic endpoints at week 12 and week 52 (all p < 0.01). In complementary analyses using data pooled from ELEVATE UC 52 and ELEVATE UC 12, among those exposed to 5-ASA/CS (N = 197), a greater proportion receiving etrasimod versus placebo met all clinical efficacy endpoints assessed at week 12 and week 52 (all p < 0.001). In those exposed to thiopurine/5-ASA/CS (N = 104), similar efficacy was observed with statistically significant differences at week 12 and numerical differences that did not reach statistical significance at week 52. Subgroup safety outcomes were similar to those in the overall population.

Conclusion: Etrasimod is an effective first-line advanced treatment option for patients with UC early in their treatment journey, after 5-ASA, thiopurine, or CS use.

Trial registration: ClinicalTrials.gov: NCT03945188, NCT03996369.

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艾特拉西莫作为溃疡性结肠炎一线高级治疗的有效性和安全性：来自ELEVATE UC临床项目的预先和事后亚组数据

背景：许多患者对溃疡性结肠炎（UC）的常规治疗反应不足或不耐受，包括5-氨基水杨酸盐（5-ASA）、硫嘌呤和皮质类固醇（CS）。Etrasimod是一种口服，每日一次（QD），选择性鞘氨醇1-磷酸（S1P）受体调节剂，用于治疗UC。目的：在不同的常规治疗方案下，我们评估了作为一线先进疗法的有效性和安全性。设计：在III期、多中心、双盲、安慰剂对照的ELEVATE UC试验中，符合条件的患者按2:1随机分配至etrasimod 2mg QD组或安慰剂组。方法：对5-ASA失败（预先指定）、5-ASA/CS（事后）和硫嘌呤/5-ASA/CS（事后）后患者亚组进行临床、内镜和组织学终点评估。在整个试验过程中对安全性进行了评估。结果：在ELEVATE uc52中，74名患者（45名接受伊特拉西莫2mg QD治疗，29名接受安慰剂治疗）先前仅发生5-ASA失败。在这些患者中，接受伊特拉西莫德治疗的患者比安慰剂治疗的患者在第12周和第52周达到临床、内窥镜和组织学终点的比例更高（所有p N = 197），接受伊特拉西莫德治疗的患者比安慰剂治疗的患者在第12周和第52周达到所有临床疗效终点的比例更高（所有p N = 104），在第12周观察到相似的疗效，差异具有统计学意义，在第52周观察到数值差异无统计学意义。亚组安全性结果与总体人群相似。结论：在5-ASA、硫嘌呤或CS治疗后，Etrasimod是早期UC患者有效的一线高级治疗选择。试验注册：ClinicalTrials.gov: NCT03945188, NCT03996369。

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来源期刊

Therapeutic Advances in Gastroenterology GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

6.70

自引率

2.40%

发文量

103

审稿时长

15 weeks

期刊介绍： Therapeutic Advances in Gastroenterology is an open access journal which delivers the highest quality peer-reviewed original research articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of gastrointestinal and hepatic disorders. The journal has a strong clinical and pharmacological focus and is aimed at an international audience of clinicians and researchers in gastroenterology and related disciplines, providing an online forum for rapid dissemination of recent research and perspectives in this area. The editors welcome original research articles across all areas of gastroenterology and hepatology. The journal publishes original research articles and review articles primarily. Original research manuscripts may include laboratory, animal or human/clinical studies – all phases. Letters to the Editor and Case Reports will also be considered.