S1507 Restarting Etrasimod After Treatment Interruption Is Not Associated With Cardiovascular Events: Analysis From the ELEVATE UC Clinical Program

Introduction: Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severe active ulcerative colitis (UC). First-dose heart rate lowering effects can occur with other S1P receptors, typically on Day 1. Cardiovascular (CV)-related treatment-emergent adverse events (TEAEs) in the ELEVATE UC clinical program were infrequent and mostly non-serious. Methods: We evaluated the CV safety of etrasimod 2 mg QD in patients (pts) in the ELEVATE UC clinical program who reinitiated etrasimod after a dose interruption >7 consecutive days. The 7-day threshold was per protocol and based on the ∼30-hour etrasimod half-life. TEAEs were recorded from Day 1 (first dose) and up to 21 days post-dose reinitiation. Per protocol, CV vital signs (heart rate and systolic and diastolic blood pressure [SBP; DBP]) were monitored at pre-dose and for ≥4 hours post-dose on Day 1 and at reinitiation after dose interruption. Results: In this analysis, 25/747 (3.3%) pts experienced a dose interruption; 17 completed ELEVATE UC 52 or ELEVATE UC 12 or were ongoing in the open-label extension at the data cut (January 31, 2022). Mean time to first dose interruption was 205.5 days (standard deviation: 165.6); mean duration of interruption was 22.4 (10.9) days. Of TEAEs that led to dose interruption (22/25), decreased lymphocyte count (n = 8/25) was the most common; no CV events led to dose interruptions. No TEAEs were within 7 days of dose reinitiation; 3 (upper respiratory tract infection, lipomatosis and migraine) were reported within 21 days. No CV events were reported. Mean changes in heart rate and SBP and DBP were consistent at 4 hours post-dose between Day 1 and day of dose reinitiation. Conclusion: Reinitiation of etrasimod after a treatment interruption >7 consecutive days was not associated with bradycardia or AV block; no CV-related events were reported on the day of reinitiation or within 21 days. CV-related TEAEs were not associated with any dose interruptions. This suggests etrasimod can safely be reinitiated after interruption in pts with moderately to severely active UC once the reason for interruption is resolved. Pfizer’s generative artificial intelligence tool MAIA was used to assist production of the abstract first draft. Authors reviewed/edited and take responsibility for the content.