Etrasimod reduces circulating and mucosal inflammatory lymphocyte populations and alters innate immune and non-immune cell signatures in intestinal mucosa: ELEVATE UC phase 3 clinical data.

Authors

Britta Siegmund, Catherine M Crosby, Rathi D Ryan, Justin Smith, Maria T Abreu, Séverine Vermeire, Iris Dotan, Keren M Rabinowitz, H Kiyomi Komori, Martina Goetsch, Karolina Wosik, John C Woolcott, Silvio Danese

Published in

Journal of Crohn's & colitis. Volume 20. Issue 10. Oct 09, 2026.

Abstract

Innate and adaptive immune cell dysregulation contributes to ulcerative colitis pathogenesis. The sphingosine 1-phosphate receptor modulator etrasimod showed efficacy in ulcerative colitis treatment in Phase 3 ELEVATE UC studies. Changes in circulating immune cells and mucosal cell types were characterized in etrasimod-treated patients with ulcerative colitis.
Blood (etrasimod n = 525, placebo n = 257 patients) and mucosal biopsies (etrasimod n = 411, placebo n = 200 patients) from patients in the ELEVATE UC trials were used to assess cellular and molecular changes for etrasimod versus placebo in clinical remitters and non-remitters using immunophenotyping, transcriptomic and proteomic techniques.
Selective and partial reduction in circulating T- and B-cell subsets was observed for etrasimod versus placebo (Week 12), with greater effects on CD4+ T cells, including Treg and Th17 cells, than CD8+ T cells, and on naive T cells and T central memory cells than T effector memory cells, without difference between remitters and non-remitters. No significant effects on monocytes nor NK cell numbers were observed. Mucosal biopsies showed corresponding reductions in T- and B-cell subsets, myeloid cells and neutrophils accompanied by downregulation of interleukin-17 and interleukin-8 signaling in both tissue and blood, most prominently in remitters, where non-immune cell changes were consistent with tissue repair.
Etrasimod treatment of patients with ulcerative colitis drives T- and B-lymphocyte subset reductions in blood and intestinal mucosa, neutrophil reductions in tissue and mucosal downregulation of inflammatory pathways associated with ulcerative colitis pathogenesis.
ClinicalTrials.gov (NCT03945188; NCT03996369).

PMID:
42864953
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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