P0756 Etrasimod efficacy in patients with mildly to moderately active Ulcerative Colitis (modified Mayo score 4–6) in the phase 3 ELEVATE UC clinical programme
Authors: Yarur A J , D'Haens G R , Baert F , Goetsch M , Zang C , Gu G , Mazur R , Keating M , Kudlacz E , Sidhu S , Wosik K , Danese S 
Published: January 2025

Background

There is an unmet need for novel advanced therapies for patients with mildly to moderately active ulcerative colitis (UC), who are most frequently treated with aminosalicylates, steroids and thiopurines. 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. This post hoc analysis evaluated the efficacy and safety of etrasimod 2 mg QD vs placebo in a subpopulation of patients from the ELEVATE UC clinical programme with mildly to moderately active UC at baseline, defined as a modified Mayo score (MMS) of 4–6.

Methods

Data were pooled from the phase 3, randomised, global ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials, and the ELEVATE UC 40 JAPAN (NCT04706793) trial.1,2 This analysis included a subset of the pooled patient population aged ≥18 years who had a baseline MMS of 4–6, including a centrally read endoscopic subscore ≥2 and a rectal bleeding subscore (RBS) ≥1. Efficacy endpoints at Week 12 and Week 52 included clinical remission, endoscopic improvement, symptomatic remission and histologic endoscopic mucosal improvement; at Week 52, sustained clinical remission and corticosteroid (CS)-free clinical remission were assessed. Least squares mean change from baseline in patient-reported outcome 2 (PRO2) score (sum of RBS and stool frequency subscores) was assessed at each visit up to Week 52. Proportions of patients with treatment-emergent adverse events (TEAEs), serious TEAEs and TEAEs leading to discontinuation were assessed.

Results

In this subgroup analysis, 221 received etrasimod and 109 received placebo. Baseline characteristics were generally balanced between treatment groups; 95 (28.8%) patients were receiving CS at baseline and 241 (73.0%) were biologic/Janus kinase inhibitor naïve. Median baseline MMS was 6.0 in both treatment groups. Significantly greater proportions of patients receiving etrasimod vs placebo achieved all efficacy endpoints at Week 12 and Week 52 (Figure). A significant decrease in PRO2 score for etrasimod vs placebo was observed as early as Week 2 and continued through to Week 32; numerically greater score decreases were observed from Week 36 to Week 52 (Table). Safety was similar between the etrasimod and placebo groups, and consistent with the overall ELEVATE UC population.1

Conclusion

Etrasimod demonstrated robust efficacy in clinical, symptomatic and endoscopic endpoints and safety consistent with the overall population in patients with mildly to moderately active UC, as defined by an MMS of 4–6.

References

1. Sandborn WJ et al. Lancet 2023; 401: 1159–1171.

2. Takeuchi K et al. Digestion 2024; ePub ahead of print.

Pfizer’s generative artificial intelligence tool MAIA was used to assist production of the abstract first draft. Authors reviewed/edited and take responsibility for the content.