Etrasimod alters blood and mucosal immune cell profiles in ELEVATE UC analysis

An analysis of the phase 3 ELEVATE UC trials characterized cellular and molecular changes associated with etrasimod, a sphingosine 1-phosphate receptor modulator, in patients with ulcerative colitis. Researchers assessed blood from 525 etrasimod-treated and 257 placebo-treated patients, and mucosal biopsies from 411 and 200 patients, respectively. Immunophenotyping, transcriptomic and proteomic techniques were used to compare treatment groups and clinical remitters with non-remitters.

At week 12, etrasimod selectively and partially reduced circulating T- and B-cell subsets versus placebo. Reductions were greater in CD4+ than CD8+ T cells, and in naive and central memory T cells than effector memory T cells. These blood changes did not differ between remitters and non-remitters. No significant effects on circulating monocyte or natural killer cell numbers were observed.

Mucosal biopsies showed reductions in T- and B-cell subsets, myeloid cells and neutrophils. Interleukin-17 and interleukin-8 signaling declined in tissue and blood, most prominently in remitters, whose non-immune cell changes were consistent with tissue repair. These findings characterize treatment-associated biological changes rather than establish additional clinical benefit. The available abstract provides no numerical effect sizes for these changes; full text was unavailable for assessment.