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
{"title":"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","authors":"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","doi":"10.1136/bmjgast-2024-001516","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)<sub>1,4,5</sub> receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). S1P<sub>1</sub> 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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>In the etrasimod UC clinical programme, IRs of cardiovascular-related TEAEs and other cardiovascular events were low. Most cardiovascular-related TEAEs were non-serious.</p><p><strong>Trial registration numbers: </strong>NCT02447302; NCT03945188; NCT03996369; NCT02536404; NCT03950232; NCT04176588.</p>","PeriodicalId":9235,"journal":{"name":"BMJ Open Gastroenterology","volume":"12 1","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748931/pdf/","citationCount":"0","resultStr":"{\"title\":\"Cardiovascular events observed among patients in the etrasimod clinical programme: an integrated safety analysis of patients with moderately to severely active ulcerative colitis.\",\"authors\":\"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\",\"doi\":\"10.1136/bmjgast-2024-001516\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)<sub>1,4,5</sub> receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). S1P<sub>1</sub> 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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>In the etrasimod UC clinical programme, IRs of cardiovascular-related TEAEs and other cardiovascular events were low. Most cardiovascular-related TEAEs were non-serious.</p><p><strong>Trial registration numbers: </strong>NCT02447302; NCT03945188; NCT03996369; NCT02536404; NCT03950232; NCT04176588.</p>\",\"PeriodicalId\":9235,\"journal\":{\"name\":\"BMJ Open Gastroenterology\",\"volume\":\"12 1\",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-01-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748931/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMJ Open Gastroenterology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1136/bmjgast-2024-001516\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMJ Open Gastroenterology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1136/bmjgast-2024-001516","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Cardiovascular events observed among patients in the etrasimod clinical programme: an integrated safety analysis of patients with moderately to severely active ulcerative colitis.
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.
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.
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