S1431 Efficacy and Safety of Etrasimod in Patients With Ulcerative Colitis Stratified by Body Mass Index: A Post Hoc Analysis From the ELEVATE UC Clinical Program

Introduction: High body mass index (BMI) may negatively impact treatment efficacy of advanced therapies, like biologics, in patients (pts) with ulcerative colitis (UC).1 The prevalence of obesity and UC have increased substantially in recent decades.23 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 UC. Methods: This post hoc analysis of ELEVATE UC 52 and ELEVATE UC 12 investigated the impact of BMI on the efficacy and safety of etrasimod in pts with UC. ELEVATE UC 52 (NCT03945188; treat-through design with 12-week [wk] induction and 40-wk maintenance periods) and ELEVATE UC 12 (NCT03996369; 12-wk induction period) were phase 3, randomized, placebo (PBO)-controlled trials.4 Pts taking ≥ 1 dose of etrasimod 2 mg QD or PBO were stratified by baseline BMI: < 25 kg/m2, 25–30 kg/m2, and > 30 kg/m2. Efficacy outcomes (per predefined outcomes) included clinical remission (primary endpoint) and selected secondary endpoints at Wk 12 (pooled) and Wk 52 (ELEVATE UC 52). Safety outcomes assessed treatment-emergent adverse event (TEAE) proportions. Results: Of the 787 pts in the ELEVATE UC clinical program, 443 (56.3%), 217 (27.6%), and 127 (16.1%) had baseline BMI < 25 kg/m2, 25–30 kg/m2, and > 30 kg/m2, respectively. Significantly more pts with BMI < 25 kg/m2 and 25–30 kg/m2 taking etrasimod vs PBO achieved all efficacy endpoints at Wks 12 and 52 (P < 0.05; Figure 1). Significantly more pts with BMI > 30 kg/m2 taking etrasimod vs PBO achieved clinical remission at Wk 52 (P < 0.0001; Wk 12: P = 0.05), endoscopic improvement and clinical response at Wks 12 and 52 (Figure 1), and corticosteroid-free clinical remission at Wk 52 (all P < 0.05). The proportions of pts with the most common TEAEs were similar between BMI subgroups taking etrasimod (Table 1). Serious AE proportions were generally similar across BMI subgroups taking etrasimod (< 25 kg/m2: 17/308 [5.5%]; 25–30 kg/m2: 8/137 [5.8%]; > 30 kg/m2: 1/82 [1.2%]). Conclusion: In the ELEVATE UC program, there were significant improvements in efficacy with etrasimod 2 mg QD vs PBO, regardless of baseline BMI. The safety profile of etrasimod was consistent between BMI subgroups and with the overall ELEVATE UC population. References: 1. Kurnool S, Nguyen NH, Proudfoot J, et al. High body mass index is associated with increased risk of treatment failure and surgery in biologic-treated patients with ulcerative colitis. Aliment Pharmacol Ther 2018; 47: 1472–1479. 2. Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 2012; 142: 46–54.e42; quiz e30. 3. Ng M, Fleming T, Robinson M, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014; 384: 766–781. 4. Sandborn WJ, D'Haens GR, Sands BE, et al. Tofacitinib for the Treatment of Ulcerative Colitis: An Integrated Summary of up to 7.8 Years of Safety Data from the Global Clinical Programme. J Crohns Colitis 2023; 17: 338–351.Figure 1.: Primary and selected secondary efficacy endpoints at Wk 12 (pooled data from ELEVATE UC 52 and ELEVATE UC 12) and at Wk 52 (ELEVATE UC 52),[a] stratified by baseline BMI. Data labels present percentage value with n/N in brackets underneath. Differences (95% CI) and 2-sided p values are based on the Cochran–Mantel–Haenszel method adjusting to reported randomization stratification of (1) naïve to biologic or Janus kinase inhibitor therapy at study entry, (2) baseline CS use (yes or no), (3) baseline disease activity (MMS: 4–6 or 7–9), and (4), for pooled Wk 12 data only, study identifier (ELEVATE UC 52 and ELEVATE UC 12). [a]Data were pooled at Wk 12 for both trials (ELEVATE UC 52 and ELEVATE UC 12); Wk 52 is ELEVATE UC 52 only. [b]Clinical remission was defined as SFS = 0 (or = 1 with a ≥ 1-point decrease from baseline), RBS = 0, and ES ≤ 1 (excluding friability). [c]Endoscopic improvement was defined as ES ≤ 1. [d]Clinical response was defined as a ≥ 2-point and ≥ 30% decrease from baseline in MMS, and a ≥ 1-point decrease from baseline in RBS or an absolute RBS ≤ 1. ∆, difference; BMI, body mass index; CI, confidence interval; CS, corticosteroid; ES, endoscopic subscore; MMS, modified Mayo score; n, number of patients; N, number of patients in the BMI subgroup; QD, once daily; RBS, rectal bleeding subscore; SFS, stool frequency subscore; UC, ulcerative colitis; Wk, Week. Table 1. - Proportions of TEAEs and events of interest reported in the pooled ELEVATE UC 52 and ELEVATE UC 12 population, stratified by baseline BMI BMI < 25 kg/m2 BMI 25–30 kg/m2 BMI > 30 kg/m2 n (%) Placebo QD (N = 135) Etrasimod 2 mg QD (N = 308) Placebo QD (N = 80) Etrasimod 2 mg QD (N = 137) Placebo QD (N = 45) Etrasimod 2 mg QD (N = 82) Any TEAE 71 (52.6) 169 (54.9) 39 (48.8) 91 (66.4) 25 (55.6) 58 (70.7) Common TEAEsa Anemia Worsening of UC Nausea Dizziness Abdominal pain Headache Arthralgia Back pain COVID-19 infection Pyrexia 12 (8.9)9 (6.7)2 (1.5)1 (0.7)7 (5.2)7 (5.2)3 (2.2)2 (1.5)3 (2.2)4 (3.0) 31 (10.1)18 (5.8)9 (2.9)7 (2.3)6 (1.9)17 (5.5)8 (2.6)3 (1.0)9 (2.9)11 (3.6) 7 (8.8)3 (3.8)2 (2.5)002 (2.5)1 (1.3)04 (5.0)4 (5.0) 5 (3.6)9 (6.6)5 (3.6)9 (6.6)6 (4.4)10 (7.3)7 (5.1)7 (5.1)7 (5.1)8 (5.8) 3 (6.7)2 (4.4)001 (2.2)02 (4.4)1 (2.2)5 (11.1)1 (2.2) 2 (2.4)4 (4.9)5 (6.1)2 (2.4)2 (2.4)8 (9.8)2 (2.4)1 (1.2)7 (8.5)3 (3.7) Serious AEs 5 (3.7) 17 (5.5) 3 (3.8) 8 (5.8) 3 (6.7) 1 (1.2) Serious infectionsb 1 (0.7) 0 2 (2.5) 3 (2.2) 2 (4.4) 0 AEs leading to treatment discontinuation 6 (4.4) 13 (4.2) 1 (1.3) 8 (5.8) 1 (2.2) 4 (4.9) Events of interest Macular edema AV block first-degree AV block second-degree Bradycardia Sinus bradycardia Cytomegalovirus infection Tuberculosis Herpes zoster 0000001 (0.7)0 1 (0.3)2 (0.6)02 (0.6)2 (0.6)1 (0.3)01 (0.3) 00000000 001 (0.7)2 (1.5)1 (0.7)001 (0.7) 1 (2.2)0000002 (4.4) 1 (1.2)001 (1.2)1 (1.2)000 For AEs with 0 patients with event, % is also 0 and is not displayed.aCommon TEAEs are defined by > 5% occurring in any subgroup.bSerious infections are serious AEs under the System Organ Class of Infections and Infestations.AE, adverse event; AV, atrioventricular; BMI, body mass index; COVID-19, coronavirus disease 2019; n, number of unique patients with events; N, number of patients in the subgroup in the analysis set by treatment; QD, once daily; TEAE, treatment-emergent adverse event; UC, ulcerative colitis.

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