Abstract Background Etrasimod is an oral, next-generation, selective modulator of sphingosine 1-phosphate receptors 1, 4, and 5, developed for the management of moderately to severely active ulcerative colitis (UC).1 This post hoc analysis evaluated the efficacy of Etrasimod 2 mg once- daily vs placebo in patients receiving prior 5-aminosalicylates and/or thiopurines in the phase 3 ENLIGHT UC study. Methods ENLIGHT UC (NCT04176588) was a randomized, double-blind, placebo-controlled, multicenter, phase 3 study in Asia adults with moderately to severely active UC and an inadequate response, loss of response, or intolerance to at least one UC therapy.2 Patients were randomized 2:1 to receive once-daily oral Etrasimod 2 mg or placebo for 12 weeks (induction period). Responders at 12 weeks were re-randomized 1:1 to Etrasimod 2 mg or placebo for 40 weeks (maintenance period). The primary endpoint, clinical remission, and secondary endpoints—endoscopic improvement, mucosal healing, and symptomatic remission—were assessed during both induction and maintenance periods. Results A total of 340 patients were included in the induction period (etrasimod vs placebo: 228 vs 112) and 157 during the maintenance period (77 vs 80) in ENLIGHT UC study. Nearly all patients (99%) had previously received 5-aminosalicylates and/or thiopurines. Specifically, 99.7% were treated with 5-aminosalicylates and 7.4% with thiopurines. Among these, bio/JAKi-naïve patients treated exclusively with 5-aminosalicylates and/or thiopurines constituted the main analysis population of this post hoc analysis, accounting for 80.3% (273/340; etrasimod vs placebo: 82.5% 188/228 vs 75.9% 85/112) of patients during induction period and 79.6% (125/157; etrasimod vs placebo: 80.5% 62/77 vs 78.8%63/80) during maintenance period. Significantly higher proportions of patients treated with etrasimod achieved clinical remission compared with placebo at induction week 12 (25.5% vs 2.4%; difference 23.9%, 95% CI 16.9–30.9; p 0.0001) and maintenance week 40 (46.8% vs 14.3%; difference 32.6%, 95% CI 17.5–47.7; p 0.0001; Table 1). Similar trends were observed for endoscopic improvement (37.2% vs 5.9% at week 12; 61.3% vs 17.5% at week 40), mucosal healing (26.6% vs 3.5% at week 12; 53.2% vs 9.5% at week 40), and symptomatic remission (39.9% vs 15.3% at week 12; 61.3% vs 31.7% at week 40), all with p 0.0001. Conclusion Etrasimod was effective as an oral induction and maintenance treatment in moderately to severely active UC patients treated with prior 5-aminosalicylates and/or thiopurines, supporting its effectiveness when used early in the UC treatment algorithm. References: 1. Shirley M. Etrasimod: First Approval. Drugs. 2024;84(2):247-254. 2. Wu K, Zhang C, Chen Q, et al. Etrasimod as induction and maintenance treatment for patients with moderately to severely active ulcerative colitis in East Asia (ENLIGHT UC): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. Lancet Gastroenterol Hepatol. 2025 Dec;10(12):1089-1103. Conflict of interest: Zheng, Changqing: No conflict of interest. Cao, Qian: No conflict of interest Ding, Yijuan: none Gao, Xiang: No conflict of interest Zhong, Jie: No conflict of interest. Zhang, Hu: No conflict of interests. Wang, Xin: No conflicts of interest Wang, Bangmao: None Zhou, Yongjian: No conflict of interest Xu, Baohong: None Prof. Wu, Kaichun: No conflict of interest
Zheng et al. (Thu,) studied this question.