Effect Of Etrasimod On Immune Cell Subsets In Colonic Tissue Of Patients With Ulcerative Colitis: Immunophenotyping Analysis Of Colon Biopsy Samples From The Phase 3 ELEVATE UC 52 And ELEVATE UC 12 Trials

By Britta Siegmund, H. Kiyomi Komori, Maria T. Abreu, Séverine Vermeire, Iris Dotan, Martina Goetsch, Catherine Crosby, Rathi Ryan, John Woolcott, and Silvio Danese

Etrasimod is an investigational, once-daily oral therapy offering a novel approach for treating moderately to severely active ulcerative colitis (UC). By reversibly sequestering specific lymphocyte subsets within lymph nodes, etrasimod reduces the number of circulating immune cells, thereby limiting their migration to the gastrointestinal tract and potentially mitigating inflammation. Prior studies have demonstrated etrasimod’s differential effects on peripheral immune cell populations, suggesting a targeted immunomodulatory profile.

However, comprehensive evaluations of its impact on immune cell infiltration and accumulation in intestinal tissues have been limited. To address this, the phase 3 ELEVATE UC program incorporated exploratory biomarker substudies within both ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369). These substudies aim to deepen understanding of etrasimod’s mechanism of action and its influence on key immunological pathways involved in UC pathogenesis. The findings may provide critical insights into how selective S1P receptor modulation can translate into clinical efficacy and inform future therapeutic strategies for immune-mediated gastrointestinal disorders.