P602 Achievement of stringent histologic and composite endpoints in subjects with moderately to severely active ulcerative colitis treated with etrasimod: a post hoc analysis of the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials

Abstract Background In ulcerative colitis (UC), persistent histological activity is associated with higher rates of relapse and long-term complications, even when endoscopic remission achieved; therefore, healing a potentially important treatment target. Etrasimod an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 (S1P1,4,5) modulator for the moderately to severely active UC. This post hoc analysis phase 3 ELEVATE programme evaluated efficacy etrasimod according different histologic composite endpoints. Methods UC 52 (NCT03945188) 12 (NCT03996369), subjects (16-80 years) were randomised 2:1 once-daily 2 mg or placebo (PBO). utilized treat-through design comprising 12-week induction period followed by 40-week maintenance period. comprised A key secondary endpoint was achievement improvement-histologic (EIHR). this (baseline MMS 5-9), compared PBO at weeks in week using additional endpoints defined Table 1. Results At 52, significant improvements observed outcomes, including EIHR (with without eosinophils), remission, histologic-endoscopic mucosal improvement (HEMI), normalization-histologic disease clearance (Figure 1). both studies, superior HEMI (ELEVATE 12: 27.7% vs 8.9%, 25.7% 10.7%, P<0.001) 52: 32.8% 8.9%; P<0.001). also (33.9% 9.6%) (30.7% 14.1%, but not 12. more stringent (week 10.6% 1.5%, P<0.001 10.4% 4.5%, P=0.030; 18.2% 5.2%; 8.4% 9.9% P=0.042; 18.6% 3.7%; Conclusion analysis, EIHR,