S1510 Efficacy of Etrasimod as First-Line Advanced Treatment Following Failure of Aminosalicylates Only: Data From the ELEVATE UC 52 Phase 3 Clinical Trial

Introduction: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). In patients with moderately to severely active UC, treatment guidelines recommend early use of advanced therapies rather than gradual step up after failure of 5-aminosalicylate (5-ASA). Methods: This prespecified subgroup analysis assessed the efficacy of etrasimod vs placebo in patients in ELEVATE UC 52 (NCT03945188) with, and without, prior oral 5-ASA failure only (defined as inadequate response, loss of response or intolerance to previous treatment with oral 5-ASA but not to any other previous UC medication). Efficacy endpoints assessed at Weeks 12 and 52 included clinical remission, endoscopic improvement, symptomatic remission and composite histological endpoints. Results: In total, 45 and 29 patients receiving etrasimod and placebo, respectively, had prior 5-ASA failure only and 244 and 115 patients did not. At Weeks 12 and 52, among those who had failed prior 5-ASA only, significantly more patients receiving etrasimod vs placebo achieved clinical remission (Week 12, % difference [Δ]: 38.3%, P < 0.001; Week 52, Δ: 45.0%, P < 0.001), endoscopic improvement (Week 12, Δ: 54.7%, P < 0.001; Week 52, Δ: 47.8%, P < 0.001), symptomatic remission (Week 12, Δ: 38.6%, P < 0.001; Week 52, Δ: 45.0%, P < 0.001), and endoscopic improvement-histologic remission (Week 12, Δ: 35.6%, P < 0.001; Week 52, Δ: 31.1%, P < 0.001). Significantly more patients receiving etrasimod vs placebo in this subgroup achieved endoscopic normalization-histologic remission (Week 12, Δ: 19.9%, P = 0.002; Week 52, Δ: 24.3%, P < 0.001) and disease clearance (Week 12, Δ: 15.6%, P = 0.008; Week 52, Δ: 27.8%, P < 0.001). Among those who had failed other therapies, significantly more patients receiving etrasimod vs placebo also achieved all endpoints at Weeks 12 and 52 (P < 0.01). Conclusion: Etrasimod demonstrated robust efficacy as first-line advanced therapy in patients who had failed oral 5-ASA only, across all evaluated endpoints including stringent composite histological endpoints, consistent with the overall ELEVATE UC population. Etrasimod shows efficacy when used early in the UC treatment algorithm. Pfizer’s generative artificial intelligence tool MAIA was used to assist production of the abstract first draft. Authors reviewed/edited and take responsibility for the content.