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 Gastroenterol. 2025 Jan 8;12(1):e001516. doi: 10.1136/bmjgast-2024-001516.

Abstract

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.

Keywords: ADVERSE DRUG REACTIONS; CARDIOVASCULAR COMPLICATIONS; ULCERATIVE COLITIS.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Atrioventricular Block* / chemically induced
  • Atrioventricular Block* / epidemiology
  • Bradycardia* / chemically induced
  • Bradycardia* / epidemiology
  • Cardiovascular Diseases* / chemically induced
  • Cardiovascular Diseases* / epidemiology
  • Colitis, Ulcerative* / drug therapy
  • Colitis, Ulcerative* / epidemiology
  • Coronary Artery Disease / drug therapy
  • Coronary Artery Disease / epidemiology
  • Double-Blind Method
  • Female
  • Humans
  • Hypertension / drug therapy
  • Hypertension / epidemiology
  • Incidence
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Sphingosine 1 Phosphate Receptor Modulators* / administration & dosage
  • Sphingosine 1 Phosphate Receptor Modulators* / adverse effects
  • Sphingosine 1 Phosphate Receptor Modulators* / therapeutic use
  • Sphingosine-1-Phosphate Receptors

Substances

  • Sphingosine 1 Phosphate Receptor Modulators
  • Sphingosine-1-Phosphate Receptors

Associated data

  • ClinicalTrials.gov/NCT02447302
  • ClinicalTrials.gov/NCT03945188
  • ClinicalTrials.gov/NCT03950232
  • ClinicalTrials.gov/NCT03996369
  • ClinicalTrials.gov/NCT02536404
  • ClinicalTrials.gov/NCT04176588