PT  - JOURNAL ARTICLE
AU  - Vermeire, Séverine
AU  - Rubin, David T
AU  - Peyrin-Biroulet, Laurent
AU  - Dubinsky, Marla C
AU  - Regueiro, Miguel
AU  - Irving, Peter M
AU  - Goetsch, Martina
AU  - Lazin, Krisztina
AU  - Gu, Guibao
AU  - Wu, Joseph
AU  - Modesto, Irene
AU  - McDonnell, Aoibhinn
AU  - Guo, Xiang
AU  - Green, Jesse
AU  - Dalam, Alexis B
AU  - Yarur, Andres J
TI  - Cardiovascular events observed among patients in the etrasimod clinical programme: an integrated safety analysis of patients with moderately to severely active ulcerative colitis
AID  - 10.1136/bmjgast-2024-001516
DP  - 2025 Jan 01
TA  - BMJ Open Gastroenterology
PG  - e001516
VI  - 12
IP  - 1
4099  - http://bmjopengastro.bmj.com//content/12/1/e001516.short
4100  - http://bmjopengastro.bmj.com//content/12/1/e001516.full
SO  - BMJ Open Gastro2025 Jan 01; 12
AB  - 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.Data are available on reasonable request. On request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions and exceptions, Pfizer may also provide access to the related individual deidentified participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information.