The investigational, selective sphingosine 1-phosphate (S1P) receptor-modulator etrasimod has demonstrated efficacy in adults with moderately-to-severely active ulcerative colitis (UC) in the phase 3 ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials. To further explore the effect of etrasimod on immune cell subsets in UC, Prof. Silvio Danese (Vita-Salute San Raffaele University, Italy) performed a per-protocol, exploratory analysis of data from the ELEVATE UC 52 and ELEVATE UC 12 studies [2].
Whole blood was collected at weeks 2, 4, 8, and every 4 weeks up to week 52 in the ELEVATE UC 52 trial and at weeks 2, 4, 8, and 12 in the ELEVATE UC 12 trial for assessment of absolute lymphocyte counts and immunophenotyping.
Patients treated with etrasimod demonstrated nearly nadir absolute lymphocyte counts by week 2 which was maintained during the treatment period through week 52 in ELEVATE UC 52 and week 12 in ELEVATE UC 12.
In addition, treatment with etrasimod resulted in rapid mean percentage reduction from baseline to week 2 with nadir and near nadir changes reached by week 4 in both trials for total T cells, T helper cells, cytotoxic T cells, and B cells. All reductions were maintained throughout the studies. In contrast, etrasimod did not influence natural killer cells or monocytes in either study.
These results indicate that etrasimod has a rapid and differential effect on the frequency of circulating immune-cell subsets in the peripheral blood in patients with moderately-to-severely active UC, through sequestration of lymphocytes in lymph nodes. Etrasimod reduces adaptive immune cells (T and B cells) in the periphery, with a greater impact on CD4+ cells than on CD8+ cells but spares innate immune cells that are important components of immune surveillance.