Etrasimod efficacy in patients with mildly to moderately active ulcerative colitis (modified Mayo score 4–6) in the phase 3 ELEVATE UC clinical programme

Introduction: 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 ulcerative colitis (UC).

Objectives: To evaluate the efficacy and safety of etrasimod 2 mg QD vs placebo (PBO) in a subpopulation of patients (pts) from the ELEVATE UC clinical programme with mildly to moderately active UC at baseline (BL).

Methodology: Data were pooled from the phase 3, randomised ELEVATE UC 52 (NCT03945188), ELEVATE UC 12 (NCT03996369) and ELEVATE UC 40 JAPAN (NCT04706793) trials [1] [2]. This post hoc analysis used a subset of pts aged≥18 years with a BL modified Mayo score (MMS) of 4–6 (with a centrally read endoscopic subscore≥2 and a rectal bleeding subscore [RBS]≥1). Efficacy endpoints at Week (Wk) 12 and Wk 52 included clinical remission, endoscopic improvement, symptomatic remission and endoscopic improvement-histologic remission (EIHR); at Wk 52, sustained clinical remission and corticosteroid (CS)-free clinical remission were assessed. Least square mean change from BL in pt-reported outcome 2 (PRO2) score (sum of RBS and stool frequency subscore) was assessed to Wk 52. Proportions of pts with treatment-emergent adverse events (TEAEs), serious TEAEs and TEAEs leading to discontinuation were assessed.

Results: In this subgroup analysis, 221 pts received etrasimod and 109 received PBO. BL characteristics were generally balanced between treatment groups; 95 (28.8%) pts were taking CS at BL; 241 (73.0%) were biologic/Janus kinase inhibitor naïve. Median BL MMS was 6.0 in both treatment groups. Significantly greater proportions of pts receiving etrasimod vs PBO achieved all efficacy endpoints at Wk 12 and Wk 52 ([Fig. 1]). A significant decrease in PRO2 score for etrasimod vs PBO was observed at Wk 2 and continued to Wk 32, with numerically greater score decreases from Wk 36 to Wk 52 ([Table 1]). Safety was similar across treatment groups, and consistent with the overall ELEVATE UC population [1].

Fig. 1  

Table 1 LS mean change from BL up to Wk 52 in PRO2 score in pts with mildly to moderately active UC (MMS 4–6)

	Pooled pt populationa
	PBO QD, LS red (SE) [n] N=109	Etrasimod 2 mg QD, LS mean (SE) [n] N=221	LS mean difference (95% CI)	p value
Wk 2	-0.60 (0.134) [102]	-1.06 (0.096) [212]	-0.46 (-0.77, -0.15)	0.004
Wk 4	-0.89 (0.131) [104]	-1.63 (0.094) [211]	-0.74 (-1.04, -0.43)	<0.001
Wk 8	-1.11 (0.137) [101]	-1.89 (0.098) [205]	-0.78 (-1.10, -0.46)	<0.001
Wk 12	-1.12 (0.144) [95]	-1.96 (0.102) [202]	-0.84 (-1.18, -0.50)	<0.001
Wk 16	-1.07 (0.216) [33]	-1.90 (0.152) [101]	-0.82 (-1.28, -0.37)	<0.001
Wk 20	-1.07 (0.211) [34]	-2.06 (0.147) [104]	-0.99 (-1.43, -0.55)	<0.001
Wk 24	-1.36 (0.213) [31]	-1.99 (0.146) [102]	-0.64 (-1.08, -0.19)	0.005
Wk 32	-1.31 (0.224) [29]	-1.88 (0.148) [99]	-0.57 (-1.04, -0.11)	0.017
Wk 40	-1.23 (0.265) [30]	-1.71 (0.171) [95]	-0.48 (-1.06, 0.09)	0.096
Wk 48	-1.30 (0.263) [27]	-1.75 (0.167) [90]	-0.45 (-1.02, 0.11)	0.116
Wk 52	-1.42 (0.249) [29]	-1.90 (0.163) [89]	-0.48 (-1.01, 0.05)	0.078

p<0.05 values are highlighted in bold. PRO2 score was defined as the sum of the RBS and SFS per individual protocol. Change from BL estimates are from an MMRM model that included BL score as a covariate and factors for study, naïve to biologic/Janus kinase inhibitor therapy at study entry (yes/no), BL CS use (yes/no), treatment, visit and the treatment by visit interaction. Data are as observed without imputation for missing values. ^aData were pooled from ELEVATE UC 52 and ELEVATE UC 12 up to Wk 12, and from ELEVATE UC 52 and ELEVATE UC 40 JAPAN after Wk 12 up to Wk 52. BL, baseline; CI, confidence interval; CS, corticosteroid; LS, least squares; MMRM, mixed model for repeated measures; MMS, modified Mayo score; N, total number of patients per treatment group; n, number of patients with assessment at the specified visit; PBO, placebo; pt, patient; PRO2, patient-reported outcome 2; QD, once-daily; RBS, rectal bleeding subscore; SE, standard error; SFS, stool frequency subscore; UC, ulcerative colitis; Wk, Week.

Conclusion: Etrasimod demonstrated robust efficacy in clinical, symptomatic and endoscopic endpoints and safety consistent with the overall population in pts with mildly to moderately active UC (MMS 4–6).

Informationen zum Einsatz von KI: Pfizer&apos;s genAI tool MAIA assisted with 1st draft development; authors assume content responsibility.

Publikationsverlauf

Artikel online veröffentlicht:
04. September 2025

• References

• 1 Sandborn WJ. et al. Lancet 2023; 401: 1159-1171
• 2 Takeuchi K. et al. Digestion 2024; ePub ahead of print.