Symptomatic Improvement Observed Within 2 Days of Etrasimod Induction Therapy: Results From ELEVATE UC 52 and ELEVATE UC 12 Studies in Patients With Ulcerative Colitis

Introduction: The time from treatment initiation to symptom relief, including rectal bleeding (RB) and stool frequency (SF), is key for patients (pts) with ulcerative colitis (UC) and can help guide therapy decisions. Etrasimod is an investigational, oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator in development for the treatment of moderately to severely active UC. Data from pt e-diaries can help inform on symptoms in pts with UC. Methods: We present a post hoc analysis of daily e-diary data collected on RB and SF from pts enrolled in the ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) phase 3 clinical trials.1 Data were pooled from the ELEVATE UC 52 and ELEVATE UC 12 studies, which randomized pts with moderately to severely active UC and an inadequate response or loss of response or intolerance to ≥ 1 approved UC therapy 2:1 to receive etrasimod 2 mg once daily or placebo (PBO). Daily Mayo RB and SF subscores (RBS and SFS) and partial modified Mayo score (pMMS; RBS + SFS) were calculated from pt e-diary responses, as well as change from baseline (CFB) during the first 28 days of therapy. Symptomatic responders were pts with ≥ 30% CFB (decrease) in pMMS. Symptomatic remission was defined as pts with RBS=0 plus SFS=0 or 1 (with ≥ 1-point improvement from baseline). RB and SF remission were defined as pts with RBS=0 and SFS=0, respectively. The Mantel–Haenszel weighted test was used to assess the adjusted risk differences in proportions of responders between treatment groups. Results: At baseline, pts receiving etrasimod and PBO had a mean (SD) RBS of 1.6 (0.69) and 1.6 (0.68), SFS of 2.4 (0.74) and 2.4 (0.74), and pMMS of 4.0 (1.07) and 4.0 (1.07), respectively. Adjusted differences in symptomatic response and symptomatic remission in pts receiving etrasimod vs PBO became significant from Day 2 (5.56 [0.79, 10.33]) and Day 11 (4.69 [0.36, 9.03]), respectively. Adjusted differences (95% confidence interval) in RB remission and SF remission in pts receiving etrasimod vs PBO reached significance from Day 15 (6.33 [0.14, 12.51]) and Day 3 (3.51 [0.87, 6.14]), respectively (all P < 0.05; Table 1). Conclusion: In this post hoc analysis of the phase 3 ELEVATE trials, we found significant, early improvements in UC symptoms in pts receiving etrasimod vs PBO beginning within 2 days. These findings indicate a potentially rapid onset of symptomatic effect with etrasimod treatment. Table 1. - Responses in Pts Receiving Etrasimod Compared with PBO on the First Day of a Significant Adjusted Difference in Daily Symptomatic Response, Symptomatic Remission, RB Remission and SF Remission Endpoint First day of significant [a] difference from PBO Pooled data from ELEVATE UC 52 and ELEVATE UC 12 Adjusted difference (95% CI) [c] 2-sided P value at first day of significant difference from PBO [d] PBO (N=260), n (%) N1 [b] Etrasimod 2 mg QD (N=527), n (%) N1 [b] Daily symptomatic response 2 27 (11.16) 242 84 (16.83) 499 5.56 (0.79, 10.33) 0.022 Daily symptomatic remission 11 21 (8.71) 241 67 (13.59) 493 4.69 (0.36, 9.03) 0.034 Daily RB remission 15 59 (25.21) 234 153 (31.35) 488 6.33 (0.14, 12.51) 0.045 Daily SF remission 3 6 (2.45) 245 31 (6.19) 501 3.51 (0.87, 6.14) 0.009 [a]Adjusted differences with nominal P values < 0.05 were considered significant.[b]N1 was the actual number of pts on each day (responders and nonresponders).[c]Adjusted differences were based on estimated common risk difference using Mantel–Haenszel weights and stratified by actual naïve to biologic/JAKi therapy at study entry (Yes/No), actual baseline corticosteroid use (Yes/No) and actual baseline disease activity (MMS: 4–6 or 7–9).[d]The Mantel–Haenszel weighted test was used to assess the adjusted risk differences in proportions of responders between treatment groups.Data were pooled from NCT03945188 and NCT03996369. Pts missing an assessment at the specified day were considered nonresponders.CI, confidence interval; JAKi, Janus kinase inhibitor; MMS, modified Mayo score; n, number of patients with characteristic; N, number of patients; PBO, placebo; pt, patient; QD, once daily; RB, rectal bleeding; SF, stool frequency; UC, ulcerative colitis. Reference: 1. Sandborn WJ et al. Lancet 2023; 401: 1159-1171.