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-emer...
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BMJ Publishing Group
2025-01-01
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| Series: | BMJ Open Gastroenterology |
| Online Access: | https://bmjopengastro.bmj.com/content/12/1/e001516.full |
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| author | Xiang Guo Peter M Irving Laurent Peyrin-Biroulet Séverine Vermeire Joseph Wu Irene Modesto David T Rubin Marla C Dubinsky Andres J Yarur Miguel Regueiro Martina Goetsch Krisztina Lazin Guibao Gu Aoibhinn McDonnell Jesse Green Alexis B Dalam |
| author_facet | Xiang Guo Peter M Irving Laurent Peyrin-Biroulet Séverine Vermeire Joseph Wu Irene Modesto David T Rubin Marla C Dubinsky Andres J Yarur Miguel Regueiro Martina Goetsch Krisztina Lazin Guibao Gu Aoibhinn McDonnell Jesse Green Alexis B Dalam |
| author_sort | Xiang Guo |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b212f7517123440db074ec0c6b1b17ac |
| institution | Kabale University |
| issn | 2054-4774 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open Gastroenterology |
| spelling | doaj-art-b212f7517123440db074ec0c6b1b17ac2025-01-09T08:50:09ZengBMJ Publishing GroupBMJ Open Gastroenterology2054-47742025-01-0112110.1136/bmjgast-2024-001516Cardiovascular events observed among patients in the etrasimod clinical programme: an integrated safety analysis of patients with moderately to severely active ulcerative colitisXiang Guo0Peter M Irving1Laurent Peyrin-Biroulet2Séverine Vermeire3Joseph Wu4Irene Modesto5David T Rubin6Marla C Dubinsky7Andres J Yarur8Miguel Regueiro9Martina Goetsch10Krisztina Lazin11Guibao Gu12Aoibhinn McDonnell13Jesse Green14Alexis B Dalam15Pfizer Inc, Collegeville, Pennsylvania, USAIBD Unit, Guy’s and St Thomas’ Hospital, London, UKDepartment of Gastroenterology, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, FranceDepartment of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, BelgiumPfizer Inc, Cambridge, Massachusetts, USAPfizer Inc, New York, New York, USAInflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, Illinois, USASusan and Leonard Feinstein IBD Center, Icahn School of Medicine at Mount Sinai, New York, New York, USAInflammatory Bowel Disease Center and Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USADepartment of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, Ohio, USAPfizer AG, Zürich, SwitzerlandPfizer AG, Zürich, SwitzerlandPfizer Inc, La Jolla, California, USAPfizer Ltd, Sandwich, Kent, UKPfizer Inc, Collegeville, Pennsylvania, USAPfizer Inc, Manila, PhilippinesObjective 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.https://bmjopengastro.bmj.com/content/12/1/e001516.full |
| spellingShingle | Xiang Guo Peter M Irving Laurent Peyrin-Biroulet Séverine Vermeire Joseph Wu Irene Modesto David T Rubin Marla C Dubinsky Andres J Yarur Miguel Regueiro Martina Goetsch Krisztina Lazin Guibao Gu Aoibhinn McDonnell Jesse Green Alexis B Dalam Cardiovascular events observed among patients in the etrasimod clinical programme: an integrated safety analysis of patients with moderately to severely active ulcerative colitis BMJ Open Gastroenterology |
| title | Cardiovascular events observed among patients in the etrasimod clinical programme: an integrated safety analysis of patients with moderately to severely active ulcerative colitis |
| title_full | Cardiovascular events observed among patients in the etrasimod clinical programme: an integrated safety analysis of patients with moderately to severely active ulcerative colitis |
| title_fullStr | Cardiovascular events observed among patients in the etrasimod clinical programme: an integrated safety analysis of patients with moderately to severely active ulcerative colitis |
| title_full_unstemmed | Cardiovascular events observed among patients in the etrasimod clinical programme: an integrated safety analysis of patients with moderately to severely active ulcerative colitis |
| title_short | Cardiovascular events observed among patients in the etrasimod clinical programme: an integrated safety analysis of patients with moderately to severely active ulcerative colitis |
| title_sort | cardiovascular events observed among patients in the etrasimod clinical programme an integrated safety analysis of patients with moderately to severely active ulcerative colitis |
| url | https://bmjopengastro.bmj.com/content/12/1/e001516.full |
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