Abstract Background Etrasimod is an orally available, small-molecule sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). The ENLIGHT UC (NCT04176588) was a randomized, double-blind, placebo-controlled, multicenter, phase 3 study conducted exclusively in the Asian population.1 The goal of UC therapy is to achieve and maintain long-term clinical and endoscopic remission. Increasingly, the concept of disease clearance (symptomatic, endoscopic, and histological remission) was recognized as the ultimate treatment goal in the treatment of UC.2 Here, we report post-hoc analyses from the ENLIGHT UC trial evaluating the efficacy of Etrasimod in achieving stringent histologic and composite endpoints in patients with moderately to severely active UC. Methods Patients with moderately to severely active UC were randomized 2:1 to once-daily Etrasimod 2 mg or placebo (induction period). Responders at 12 weeks were re-randomized 1:1 to Etrasimod 2 mg or placebo for 40 weeks (maintenance period). Histologic and composite endpoints, including disease clearance (endoscopic/histologic/symptomatic remission), were evaluated at induction week 12 and maintenance week 40. Results A total of 340 patients (228 in the Etrasimod group, 112 in the placebo group) were included during the induction week 12, and 157 (77, 80) patients who achieved clinical respond were included during the maintenance week 40. Baseline demographic and clinical characteristics were similar between both treatment groups. A significantly greater proportion of patients receiving Etrasimod achieved disease clearance compared with placebo at both week 12 (7.9% vs. 1.8%; p = 0.0038) andweek 40 (32.5% vs. 8.8%; p = 0.0001; Figure 1). Furthermore, Etrasimod consistently showed greater endoscopic and histologic improvement than placebo at week 12 (35.1% vs. 8%; p 0.0001) and week 40 (57.1% vs. 11.3%; p 0.0001). Similarly, Etrasimod was superior to placebo according to endoscopic improvement-histologic remission allowing eosinophils (33.3% vs. 6.3% at week 12; 55.8% vs. 11.3% at week 40; both p 0.0001), endoscopic and histologic remission with eosinophils (13.2% vs. 1.8%; 44.2% vs. 10%; both p 0.0001), and endoscopic and histologic remission without eosinophils (11.4% vs. 0.9%; 41.6% vs. 7.5%; both p 0.0001). Conclusion Etrasimod was effective in resolving colonic inflammation, as assessed by the stringent histologic and composite outcomes, including disease clearance. These findings further support Etrasimod as a promising treatment option for patients with moderately to severely active UC to achieve long-term treat goal. References: 1. 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. 2. D’Amico F, Magro F, Siegmund B, et al. Disease clearance as a new outcome in ulcerative colitis: a systematic review and expert consensus. Inflamm Bowel Dis. 2024;30(6):1009–1017. Conflict of interest: Zhang, Hu: No conflict of interests. Zheng, Changqing: no conflict o Cao, Qian: No conflict of interest Ding, Yijuan: none Gao, Xiang: No conflict of interest Zhong, Jie: No conflict of interest. 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
Zhang et al. (Thu,) studied this question.