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
In brief
Etrasimod lowers T and B cells in blood and gut
In phase 3 ulcerative colitis trials, etrasimod reduced selected T- and B-cell populations in blood and intestinal tissue, and lowered tissue neutrophils and inflammatory signaling. These immune changes appeared in patients who did and did not achieve remission; remission was also linked to tissue-repair signatures, but the findings do not show which changes drive clinical benefit.
- Journal
- Journal of Crohn's & colitis (Q1)
- Published
- 9 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Britta Siegmund, Catherine M Crosby, Rathi D Ryan, Justin Smith, Maria T Abreu, Séverine Vermeire, et al.
- PMID
- 42864953
- DOI
- 10.1093/ecco-jcc/jjag159
Why clinicians should know about it
- Picked for Immunology and Allergy (top studies of the week, 18 October 2026): Phase 3 RCT, reduces mucosal T cells
- Picked for Gastroenterology (top studies of the week, 18 October 2026): Phase III RCT, ulcerative colitis biologic
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).
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.