Cardiovascular events observed among patients in the etrasimod clinical programme: an integrated safety analysis of patients with moderately to severely active ulcerative colitis.

IF 3.3 Q2 GASTROENTEROLOGY & HEPATOLOGY BMJ Open Gastroenterology Pub Date : 2025-01-08 DOI:10.1136/bmjgast-2024-001516

Séverine Vermeire, David T Rubin, Laurent Peyrin-Biroulet, Marla C Dubinsky, Miguel Regueiro, Peter M Irving, Martina Goetsch, Krisztina Lazin, Guibao Gu, Joseph Wu, Irene Modesto, Aoibhinn McDonnell, Xiang Guo, Jesse Green, Alexis B Dalam, Andres J Yarur

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Abstract

Objective: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). S1P₁ receptor expression on cardiac cells is involved in cardiac conduction. We report cardiovascular treatment-emergent adverse events (TEAEs) associated with S1P receptor modulators and other cardiovascular events in the etrasimod UC clinical programme.

Methods: Patients were analysed in the Placebo-controlled UC cohort and All UC cohort. Incidence rates (IRs, per 100 patient-years) of cardiovascular-related TEAEs associated with S1P receptor modulators, including bradycardia/atrioventricular (AV) block and hypertension, and other cardiovascular events, including coronary artery disease (CAD) and cerebrovascular disease (CVD), were analysed.

Results: In patients receiving etrasimod, cardiovascular-related TEAEs were infrequent (≤2.6% per AE). In the Placebo-controlled UC cohort, IRs (95% CIs) for cardiovascular-related TEAEs were higher for patients receiving etrasimod (n=577) vs placebo (n=314), respectively, for bradycardia/sinus bradycardia, 3.85 (1.58 to 6.13) vs 0 and AV block, 1.40 (0.03 to 2.76) vs 0; and numerically higher for hypertension, 5.31 (2.62 to 7.99) vs 3.40 (0.07 to 6.72). Most bradycardia/AV block events were reported on day 1. All bradycardia and hypertension TEAEs were non-serious. One serious second-degree AV block type 1 TEAE occurred in the etrasimod group; no events of second-degree AV block type 2 or higher were reported. One event each of CAD and CVD occurred in two patients receiving etrasimod.

Conclusions: In the etrasimod UC clinical programme, IRs of cardiovascular-related TEAEs and other cardiovascular events were low. Most cardiovascular-related TEAEs were non-serious.

Trial registration numbers: NCT02447302; NCT03945188; NCT03996369; NCT02536404; NCT03950232; NCT04176588.

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在伊特拉西莫临床项目中观察到的心血管事件：对中度至重度活动性溃疡性结肠炎患者的综合安全性分析

目的：Etrasimod是一种口服，每日一次，选择性鞘氨醇1-磷酸（S1P）1,4,5受体调节剂，用于治疗中度至重度活动性溃疡性结肠炎（UC）。心脏细胞上S1P1受体的表达参与心脏传导。我们报告了在etrasimod UC临床项目中与S1P受体调节剂和其他心血管事件相关的心血管治疗突发不良事件（teae）。方法：将患者分为安慰剂对照UC组和All UC组进行分析。分析了与S1P受体调节剂相关的心血管相关teae的发病率（IRs，每100患者年），包括心动过缓/房室传导阻滞和高血压，以及其他心血管事件，包括冠状动脉疾病（CAD）和脑血管疾病（CVD）。结果：在接受伊特拉西莫的患者中，心血管相关的teae不常见（每个AE≤2.6%）。在安慰剂对照的UC队列中，接受etrasimod （n=577）的患者心血管相关teae的IRs （95% ci）高于安慰剂（n=314），对于心动过缓/窦性心动过缓，分别为3.85（1.58至6.13）和1.40(0.03至2.76)vs 0；高血压患者的数值更高，为5.31 (2.62 - 7.99)vs 3.40（0.07 - 6.72）。大多数心动过缓/房室传导阻滞发生在第1天。所有心动过缓和高血压teae均不严重。伊拉西莫德组发生1例严重的二度房室传导阻滞1型TEAE；未见2型或以上二级房室传导阻滞事件的报道。接受伊特拉西莫德治疗的2例患者中，CAD和CVD各发生1例。结论：在依特拉西莫UC临床方案中，心血管相关teae和其他心血管事件的IRs较低。大多数与心血管相关的teae不严重。试验注册号：NCT02447302；NCT03945188;NCT03996369;NCT02536404;NCT03950232;NCT04176588。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMJ Open Gastroenterology GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

5.90

自引率

3.20%

发文量

审稿时长

2 weeks

期刊介绍： BMJ Open Gastroenterology is an online-only, peer-reviewed, open access gastroenterology journal, dedicated to publishing high-quality medical research from all disciplines and therapeutic areas of gastroenterology. It is the open access companion journal of Gut and is co-owned by the British Society of Gastroenterology. The journal publishes all research study types, from study protocols to phase I trials to meta-analyses, including small or specialist studies. Publishing procedures are built around continuous publication, publishing research online as soon as the article is ready.