Advanced therapies have transformed the management of ulcerative colitis, but subgroups of patients do not respond to available treatments and have systemic side- effects, indicating the necessity for further therapeutic approaches.Sphingosine-1-phosphate (S1P) receptor agonists bind to S1P receptor-expressing activated lymphocytes, leading to retention of lymphocytes within the lymph nodes, peripheral lymphopenia, and inhibition of lymphocyte trafficking to sites of inflammation.In The Lancet , William J Sandborn and colleagues 5 present the results of two independent randomised, multicentre, double-blind, placebo-controlled, phase 3 trials of the orally once-daily selective S1P 1,4,5 agonist etrasimod in patients with moderate to severely active ulcerative colitis.The primary endpoint of clin. remission at weeks 12 and 52 was reached with statistical significance for etrasimod vs. placebo in ELEVATE UC 52 (74 [27%] of 274 patients vs ten [7%] of 135 patients; p<0·0001; and 88 [32%] of 274 patients vs nine [7%] of 135 patients; p<0·0001, resp.) and at week 12 in ELEVATE UC 12 (55 [25%] of 222 patients vs 17 [15%] of 112 patients). Key secondary endpoints supported the efficacy of etrasimod. Overall, etrasimod was well tolerated by patients.Etrasimod could further expand the therapeutic armamentarium for ulcerative colitis and positioning of this therapy in treatment algorithms will require more data.