BMJ open gastroenterology · 2025
Cardiovascular events observed among patients in the etrasimod clinical programme: an integrated safety analysis of patients with moderately to severely active ulcerative colitis.
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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
Аннотация
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.
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.
Предметные рубрики MeSH
AdultFemaleHumansMaleMiddle AgedAtrioventricular BlockBradycardiaCardiovascular DiseasesColitis, UlcerativeCoronary Artery DiseaseDouble-Blind MethodHypertensionIncidenceSeverity of Illness IndexSphingosine 1 Phosphate Receptor ModulatorsSphingosine-1-Phosphate ReceptorsRandomized Controlled Trials as TopicMulticenter Studies as TopicClinical Trials, Phase II as TopicClinical Trials, Phase III as Topic