S1164 Bowel Urgency and Abdominal Pain in Patients With Moderately to Severely Active Ulcerative Colitis in the Etrasimod ELEVATE UC Clinical Program: A Post Hoc Analysis

Introduction: Abdominal pain (AP) and bowel urgency (BU) are ulcerative colitis (UC) symptoms that result in quality of life impairment.1 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. Efficacy was demonstrated in the ELEVATE UC clinical program. Methods: The treatment effect of etrasimod vs placebo (PBO) on AP and BU was assessed as a post hoc analysis of the ELEVATE UC program. In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), patients (pts) were randomized 2:1 to once-daily etrasimod 2 mg or PBO. ELEVATE UC 52 had a treat-through design with a 12-week (wk) induction followed by a 40-wk maintenance period. ELEVATE UC 12 was a 12-wk induction study. In both trials, AP and BU data were assessed as pt-reported outcomes (PROs) at baseline (BL), Wks12 (both trials) and 52 (ELEVATE UC 52 only) using two 11-point numeric rating scales (NRS). The NRSs measured the worst AP and the severity of urgency to have a bowel movement in the past 24 hours and ranged from 0 (no pain or urgency) to 10 (pain as bad as can imagine or worst possible urgency). Endpoints included AP NRS=0, and, for pts with BL BU score ≥ 3: BU NRS clinically meaningful improvement (≥ 3 point decrease from BL) or remission (BU NRS ≤ 1).2 Results: At BL, the mean NRS scores ranged from 4.2 to 4.6 for AP and from 6.4 to 6.8 for BU across treatment arms and studies (Table 1). Significantly greater proportions of etrasimod- vs PBO-treated pts had no AP at Wk12 (ELEVATE UC 12: 33.2% vs 18.1%; ELEVATE UC 52: 27.7% vs 15.3%) and Wk52 (ELEVATE UC 52: 22.8% vs 10.4%) (all P< 0.01; Table 1). Similarly, significantly greater proportions of etrasimod- vs PBO-treated pts had no BU in both trials at Wk12 (18.1% vs 9.8%; 16.9% vs 6.7%, all P< 0.05), the difference did not meet statistical significance at Wk52 (ELEVATE UC 52: 17.3% vs 10.1%, P=0.0573; Table 1). In both trials, a significantly greater proportion of etrasimod- vs PBO-treated pts reported a BU NRS score of ≤ 1 and a decrease from BL of ≥ 3 points at Wk12 (both ELEVATE UC trials) and Wk52 (ELEVATE UC 52; all P< 0.05; Figure 1). Conclusion: Etrasimod improved AP and BU scores compared to PBO; a numerically greater proportion of etrasimod-treated pts reported no AP or no BU or had clinically meaningful decreases in BU at Wks12 and 52. References: 1. Hibi T et al. Inflamm Intest Dis 2020; 5: 27–35. 2. Dubinsky MC et al. J Patient Rep Outcomes 2022; 6: 114. Table 1. - AP and BU in ELEVATE UC 52 and ELEVATE UC 12 (FAS; BL MMS 4–9) ELEVATE UC 52 ELEVATE UC 12 PBO QD (N=144) Etrasimod 2 mg QD (N=289) Diff (95% CI) p value [a],[b] PBO QD (N=116) Etrasimod 2 mg QD (N=238) Diff (95% CI) p value [a],[b] Worst AP (NRS) in past 24 hr at BL, N1 Mean (SD) 1314.4 (2.83) 2724.6 (2.74) NA 1114.4 (2.75) 2214.2 (2.74) NA AP NRS=0Wk 12, n/N (%) 22/144 (15.3) 80/289 (27.7) 12.45 (4.64, 20.26)0.0018 21/116 (18.1) 79/238 (33.2) 14.97 (5.81, 24.13)0.0014 AP NRS=0Wk 52, n/N (%) 15/144 (10.4) 66/289 (22.8) 12.27 (5.39, 19.15)0.0005 NA NA NA Severity of urgency (NRS) in past 24 hr at BL, N1 Mean (SD) 1316.8 (2.61) 2726.8 (2.43) NA 1116.4 (2.48) 2216.4 (2.64) NA BU NRS=0Wk 12, n/N2 (%) 8/119 (6.7) 43/255 (16.9) 10.50 (3.99, 17.02)0.0016 10/102 (9.8) 36/199 (18.1) 8.18 (0.45, 15.9)0.0380 BU NRS=0Wk 52, n/N2 (%) 12/119 (10.1) 44/255 (17.3) 7.06 (-0.22, 14.34)0.0573 NA NA NA Missing responses are considered as non-responses.[a]Difference in response proportion (etrasimod vs PBO) is based on Cochran-Mantel-Haenszel method.[b]Two-sided nominal p values are reported without adjustment for multiple comparisons.AP, abdominal pain; BL, baseline; BU, bowel urgency; CI, confidence interval; Diff, difference; FAS, full analysis set; hr, hours; MMS, modified Mayo score; n, number of responders; N, number of patients in the FAS; N1, number of patients with observations at baseline; N2: number of patients with BL BU NRS score ≥ 3 points included in the analysis of BU NRS=0; NA, not applicable; NRS, numerical rating scale; PBO, placebo; QD, once daily; SD, standard deviation; Wk, week. Figure 1.: Proportions of Patients with (A) BU Remission (BU NRS of ≤ 1) and (B) a Clinically Meaningful Improvement (BU NRS ≥ 3 Point Decrease from BL) in BU Among Patients with a BL BU NRS Score ≥ 3 in ELEVATE UC 52 and ELEVATE UC 12. Missing responses are considered as non-responses Δ: adjusted difference in response rates for etrasimod vs PBO; BL, baseline; BU, bowel urgency; CI, confidence internal; PBO, placebo; n, number of responders; N2: number of patients with BL BU NRS score ≥ 3 points included in the analyses of BU NRS ≤ 1 and decrease from BL in BU NRS ≥ 3 points; NRS, numerical rating scale, QD, once daily; UC, ulcerative colitis; Wk, week.

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