Bowel Urgency in Ulcerative Colitis Is Associated With Clinical Endpoints, Health-Related Quality of Life, and Biomarkers: Data From the Etrasimod ELEVATE UC 52 Trial

Abstract Background Bowel urgency (BU) is a disruptive ulcerative colitis (UC) symptom. Etrasimod, a sphingosine 1-phosphate (S1P)1,4,5 receptor modulator, improved BU in the ELEVATE UC clinical program. Methods We assessed associations between BU and efficacy endpoints, health-related quality of life (HRQoL), and biomarkers (Weeks 12 and 52) in patients receiving etrasimod in ELEVATE UC 52. A patient-reported numerical rating scale (NRS; 0–10; none to worst BU) assessed BU at baseline, Week 12, and Week 52. Binary BU outcomes were BU remission (NRS ≤1), clinically meaningful improvement in BU (NRS ≥3-point decrease), and complete BU remission (NRS=0). Results At Week 12, etrasimod-treated patients with BU remission were 4.0 times more likely to be in clinical remission (odds ratio [95% confidence interval (CI)]: 4.0 [2.3–7.1]; p<0.0001) and 3.6 times more likely to show endoscopic improvement (3.6 [2.1–6.2]; p<0.0001) versus patients without BU remission. Patients with BU remission also had significantly greater improvement in Inflammatory Bowel Disease Questionnaire: Total score (least squares mean difference [95% CI] 21.8 [13.5–30.1], p<0.0001) and significantly lower fecal calprotectin and high-sensitivity C-reactive protein (mean [standard deviation] 744.5 [1758.0] vs 2314.2 [5182.2] and 3.2 [5.8] vs 10.5 [24.9], respectively, both p<0.0001). Similar association was seen for clinically meaningful improvement in BU and complete BU remission at Week 12 and all BU outcomes at Week 52. Conclusions In etrasimod-treated patients, bowel urgency outcomes are positively associated with efficacy endpoints, HRQoL scores, and inflammatory biomarkers, and may be surrogate markers of disease activity and HRQoL improvement. ClinicalTrials.gov NCT03945188