Sphingosine-1 Phosphate Receptor Modulators: The Next Wave of Oral Therapies in Inflammatory Bowel Disease

The armamentarium of medical therapy for inflammatory bowel disease (IBD) has expanded significantly during the past decade. A major change has been the introduction of novel, orally targeted, small molecule therapies, which are promising alternatives to traditional biomolecular drugs. Sphingosine-1 phosphate (S1P) receptor-modulating therapies are the newest class of oral small molecules to be approved by the US Food and Drug Administration (FDA) for the treatment of ulcerative colitis (UC) and are currently being studied in Crohn's disease. They work by targeting the interaction between S1P and S1P1 receptors, which regulate lymphocyte egress from the spleen and lymph nodes into the systemic circulation, thereby reducing intestinal inflammation in IBD. In May 2021, ozanimod was the first S1P receptor modulator approved by the FDA for the treatment of moderately to severely active UC. This article summarizes the mechanism of action, efficacy, and safety of S1P receptor modulators based on currently available clinical studies as well as examines practical considerations and positioning in treating patients with UC.