P582 Efficacy of etrasimod at week 52 among subjects who reached clinical response at week 12: post hoc analysis of the phase 3 ELEVATE UC 52 trial
Vermeire, S.(1)*;Sands, B.E.(2);Dubinsky, M.C.(3);Feagan, B.G.(4);Panaccione, R.(5);Jairath, V.(6);Yarur, A.(7);Chiorean, M.(8);Panés, J.(9);Goetsch, M.(10);Rabbat, C.J.(11);Shah, P.(12);Wu, J.(13);Ghosh, S.(14);
(1)University Hospitals Leuven, Gastroenterology, Leuven, Belgium;(2)Dr. Henry D. Janowitz Division of Gastroenterology- Icahn School of Medicine at Mount Sinai, Gastroenterology, New York- New York, United States;(3)Feinstein IBD Center- Mount Sinai, Gastroenterology, New York- New York, United States;(4)University of Western Ontario/Alimentiv Inc, Gastroenterology, London- Ontario, Canada;(5)Inflammatory Bowel Disease Unit- Division of Gastroenterology and Hepatology- University of Calgary, Gastroenterology and Hepatology, Calgary- Alberta, Canada;(6)Western University, Gastroenterology, London- Ontario, Canada;(7)Cedars-Sinai Medical Center, Gastroenterology, Los Angeles- California, United States;(8)IBD Center- Swedish Medical Center, Gastroenterology, Seattle- Washington, United States;(9)Hospital Clínic de Barcelona- IDIBAPS- CIBERehd, Gastroenterology, Barcelona, Spain;(10)Pfizer AG, Global Clinical Development, Zurich, Switzerland;(11)Pfizer Inc, Global Medical Affairs- Gastroenterology, New York- New York, United States;(12)Pfizer Inc, US Medical Affairs- Inflammation & Immunology, Collegeville- Pennsylvania, United States;(13)Pfizer Inc, Biostatistics, Groton- Connecticut, United States;(14)College of Medicine and Health- University College Cork, Gastroenterology, Cork, Ireland;
Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 (S1P1,4,5) modulator in development for the treatment of ulcerative colitis (UC). The ELEVATE UC 52 trial utilized a treat-through design which evaluated efficacy at week 52 among all subjects randomised from baseline. Here, we report a post hoc analysis of efficacy at week 52 among subjects who did or did not achieve clinical response at the end of the 12-week induction period in ELEVATE UC 52.
In ELEVATE UC 52 (NCT03945188), subjects (16-80 years) with moderately to severely active UC were randomised 2:1 to once-daily etrasimod 2 mg or placebo (PBO). This post hoc analysis assessed achievement of clinical remission, 12-week corticosteroid-free remission, endoscopic improvement, endoscopic improvement-histologic remission, and symptomatic remission at week 52 among subjects with baseline MMS 5-9 who did or did not achieve clinical response criteria at week 12 (defined as a ≥2-point and ≥30% decrease from baseline in MMS and a ≥1-point decrease from baseline in rectal bleeding subscore or an absolute rectal bleeding subscore ≤1).
At week 12 in ELEVATE UC 52, 171 (62.4%) etrasimod-treated subjects vs 46 (34.1%) PBO-treated subjects achieved clinical response (P<0.001) and were included in the week 52 clinical responder analysis. Among clinical responders at week 12, subjects treated with etrasimod were more likely to be in clinical remission at week 52 vs PBO (49.1% [n=84/171] vs 17.4% [n=8/46]; P<0.001) (Figure 1). Similar results were observed for the achievement of all other efficacy endpoints at week 52 among those who met clinical response criteria at week 12 (all P<0.05). At week 12 in ELEVATE UC 52, 103 (37.6%) etrasimod-treated subjects and 89 (65.9%) PBO-treated subjects either did not achieve clinical response at week 12 or had discontinued the study prior to the week 12 assessment. There were no significant treatment differences in achievement of efficacy endpoints at week 52 among subjects who did not achieve clinical response at week 12.
Among subjects who reached clinical response criteria at week 12, greater proportions of etrasimod-treated subjects vs PBO-treated subjects achieved week 52 efficacy across both objective and subjective measures of disease activity. Among subjects who did not reach clinical response or had discontinued prior to week 12, no significant treatment differences were observed at week 52 between etrasimod-treated subjects vs PBO-treated subjects. These results may help contextualize the 52-week efficacy results of ELEVATE UC 52 when considering other treatments that utilized re-randomisation of responder designs.