S1P receptors in ulcerative colitis: spotlight on Etrasimod

INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a rising global incidence. Small molecules have transformed the treatment of UC. Specifically, sphingosine 1-phosphate (S1P) receptor modulators are a newly available and expanding therapeutic option for patients with UC. AREAS COVERED: This review analyzes the biology, efficacy, and safety of S1P receptor modulators.A literature search in PUBMED regarding clinical studies, published up to 1 June 2026, involving S1P receptor modulators in UC was analyzed. Clinical trial data and real-world evidence for approved S1P receptor modulators (ozanimod and etrasimod) and investigational agents (tamuzimod, mocravimod, and amiselimod) in UC treatment were gathered ozanimod and etrasimod both demonstrated superior efficacy over placebo in moderately to severely active UC. Both agents showed greater efficacy in biologic-naïve patients compared to biologic-exposed populations. Meta-analyses favored S1P receptor modulators over other UC therapies, particularly for inducing histologic improvement. Commonly reported adverse effects of S1P receptor modulators include elevated liver enzymes, and transient asymptomatic bradycardia. Serious adverse events, including macular edema and severe infections, are rare, with infection rates comparable to those of placebo in the clinical trials. EXPERT OPINION: S1P receptor modulators represent a new and promising oral class of treatment for UC, showing effective results with a manageable safety profile. They are especially beneficial for patients with moderate disease severity and serve as an important option for those transitioning from traditional to advanced therapies. Although these agents have some unique safety concerns, most are mild and reversible.