The efficacy and safety of etrasimod as a first-line advanced therapy for ulcerative colitis: prespecified and post hoc subgroup data from the ELEVATE UC clinical program

Background: Many patients show inadequate response or intolerance to conventional therapies for ulcerative colitis (UC), including 5-aminosalicylates (5-ASA), thiopurines, and corticosteroids (CS). Etrasimod is an oral, once daily (QD), selective sphingosine 1-phosphate (S1P) receptor modulator for the treatment of UC. Objectives: We assessed efficacy and safety as a first-line advanced therapy following different scenarios of conventional treatment. Design: In the phase III, multicenter, double-blind, placebo-controlled ELEVATE UC trials, eligible patients were randomized 2:1 to etrasimod 2 mg QD or placebo. Methods: Subgroups of patients post-5-ASA failure (prespecified), post-5-ASA/CS (post hoc), and post-thiopurine/5-ASA/CS (post hoc) were assessed for clinical, endoscopic, and histologic endpoints. Safety was assessed throughout the trials. Results: In ELEVATE UC 52, 74 patients (45 receiving etrasimod 2 mg QD and 29 receiving placebo) had prior failure of 5-ASA only. Among these patients, a greater proportion of those treated with etrasimod versus placebo met clinical, endoscopic, and histologic endpoints at week 12 and week 52 (all p < 0.01). In complementary analyses using data pooled from ELEVATE UC 52 and ELEVATE UC 12, among those exposed to 5-ASA/CS ( N = 197), a greater proportion receiving etrasimod versus placebo met all clinical efficacy endpoints assessed at week 12 and week 52 (all p < 0.001). In those exposed to thiopurine/5-ASA/CS ( N = 104), similar efficacy was observed with statistically significant differences at week 12 and numerical differences that did not reach statistical significance at week 52. Subgroup safety outcomes were similar to those in the overall population. Conclusion: Etrasimod is an effective first-line advanced treatment option for patients with UC early in their treatment journey, after 5-ASA, thiopurine, or CS use. Trial registration: ClinicalTrials.gov: NCT03945188, NCT03996369.