Vermeire Séverine, Rubin David T, Peyrin-Biroulet Laurent, Dubinsky Marla C, Regueiro Miguel, Irving Peter M, Goetsch Martina, Lazin Krisztina, Gu Guibao, Wu Joseph, Modesto Irene, McDonnell Aoibhinn, Guo Xiang, Green Jesse, Dalam Alexis B, Yarur Andres J
Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.
Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, Illinois, USA.
BMJ Open Gastroenterol. 2025 Jan 8;12(1):e001516. doi: 10.1136/bmjgast-2024-001516.
Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P) receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). S1P 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.
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.
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.
In the etrasimod UC clinical programme, IRs of cardiovascular-related TEAEs and other cardiovascular events were low. Most cardiovascular-related TEAEs were non-serious.
NCT02447302; NCT03945188; NCT03996369; NCT02536404; NCT03950232; NCT04176588.
艾曲莫德是一种口服、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溃疡性结肠炎（UC）。心脏细胞上的S1P受体表达与心脏传导有关。我们报告了在艾曲莫德UC临床研究项目中与S1P受体调节剂相关的心血管治疗突发不良事件（TEAE）以及其他心血管事件。
在安慰剂对照的UC队列和所有UC队列中对患者进行分析。分析了与S1P受体调节剂相关的心血管相关TEAE的发生率（IR，每100患者年），包括心动过缓/房室（AV）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）。
在接受艾曲莫德治疗的患者中，心血管相关TEAE发生率较低（每种AE≤2.6%）。在安慰剂对照的UC队列中，接受艾曲莫德治疗的患者（n = 577）与安慰剂组（n = 314）相比，心血管相关TEAE的IR（95%CI）在心动过缓/窦性心动过缓方面分别为3.85（1.58至6.13）对0，AV阻滞方面为1.40（0.03至2.76）对0；高血压方面数值更高，分别为5.31（2.62至7.99）对3.40（0.07至6.72）。大多数心动过缓/AV阻滞事件在第1天报告。所有心动过缓和高血压TEAE均不严重。艾曲莫德组发生1例严重的1型二度AV阻滞TEAE；未报告2型或更高程度的二度AV阻滞事件。在两名接受艾曲莫德治疗的患者中分别发生1例CAD和CVD事件。
在艾曲莫德UC临床研究项目中，心血管相关TEAE和其他心血管事件的IR较低。大多数心血管相关TEAE不严重。
NCT02447302；NCT03945188；NCT03996369；NCT02536404；NCT03950232；NCT04176588。
