S1933 Bowel Urgency Outcomes Are Associated With Clinical Outcomes, Health-Related Quality of Life and Biomarkers in the Etrasimod ELEVATE UC 52 Clinical Trial

Introduction: Etrasimod is an oral, once-daily (QD), selective sphingosine 1 phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Etrasimod 2 mg QD improved bowel urgency (BU) at Weeks (Wks) 12 and 52 in the ELEVATE UC clinical program. Methods: We assessed associations between BU and efficacy endpoints, health-related quality of life (HRQoL) and biomarkers in patients receiving etrasimod in ELEVATE UC 52 (NCT03945188). BU was assessed at baseline (BL), Wk 12 and Wk 52 via a patient-reported, 11-point Urgency Numerical Rating Scale (NRS; 0–10; none to worst possible BU). We defined patient subgroups as with/without BU remission (NRS ≤1) or clinically meaningful improvement (CMI) in BU (NRS ≥ 3-point decrease from BL) at Wks 12 and 52. Associations were assessed between BU remission or CMI in BU (yes/no) and binary efficacy endpoints (multivariable logistic regression), change from BL in HRQoL using the inflammatory bowel diseases questionnaire total score and 36-item short form survey physical and mental component scores (multivariable linear regression) and fecal calprotectin (fCAL; Wilcoxon Rank test) at Wks 12 and 52. Results: A larger proportion of patients with BU remission (73.6%) and CMI in BU (78.9%) at Wk 12 were naïve to biologic/Janus kinase inhibitors vs experienced. At Wk 12, significantly more patients with vs without BU remission met efficacy endpoints (odds ratio, OR [95% confidence interval, CI]: clinical remission 4.0 [2.3, 7.1]; endoscopic improvement 3.6 [2.1, 6.2]; both P < 0.0001) and had significantly greater improvement in HRQoL scores and lower fCAL (all P < 0.05). A similar association was seen for CMI in BU at Wk 12 (OR [95% CI]: clinical remission 3.7 [2.1, 6.4]; endoscopic improvement 2.6 [1.6, 4.3]; both P < 0.001) and for patients meeting BU outcomes at Wk 52. Conclusion: Bowel urgency outcomes were associated with improvements in clinical and endoscopic endpoints, HRQoL scores and reduced fCAL at Wks 12 and 52. With etrasimod, BU outcomes may be surrogate markers of disease activity and HRQoL improvement. 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.