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
Journal of Crohn's and Colitis, 2026
Siegmund B., Crosby C., Ryan R., Smith J., Abreu M., Vermeire S., Dotan I., Rabinowitz K., Komori H., Goetsch M., Wosik K., Woolcott J., Danese S.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
Background and Aims
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.
Methods
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.
Results
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.
Conclusions
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.
Clinical trials registration number
ClinicalTrials.gov (NCT03945188; NCT03996369).