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 < .0001) and 3.6 times more likely to show endoscopic improvement (3.6 [2.1-6.2]; P < .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 < .0001) and significantly lower fecal calprotectin and high-sensitivity C-reactive protein (mean [standard deviation] 744.5 [1,758.0] vs 2,314.2 [5,182.2] and 3.2 [5.8] vs 10.5 [24.9], respectively, both P < .0001). A 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.

Clinicaltrialsgov: NCT03945188.