S1PR Modulators in the Management of Ulcerative Colitis: Considerations for Practice

Aaron Hass; Laetitia Amar; Robert Battat

doi:10.58931/cibdt.2024.2333

Authors

Aaron Hass, MD Division of Gastroenterology, Department of Medicine, Centre hospitalier de l'Université de Montréal, Montreal, Canada.
Laetitia Amar, MD Division of Gastroenterology, Department of Medicine, Centre hospitalier de l'Université de Montréal, Montreal, Canada.
Robert Battat, MD, FRCPC Division of Gastroenterology, Department of Medicine, Centre hospitalier de l'Université de Montréal, Montreal, Canada.

DOI:

https://doi.org/10.58931/cibdt.2024.2333

Abstract

Sphingosine-1-phosphate receptor (S1PR) modulators are novel oral small-molecule therapies that offer a unique profile compared to other advanced therapies in the treatment of ulcerative colitis (UC), including oral administration, linear pharmacokinetic profiles, reduced immunogenicity, and lower costs associated with manufacturing.

The activation of S1P G-protein coupled receptors plays an inflammatory role in UC by promoting lymphocyte egress from lymphoid organs into circulation and colonic mucosa. S1PR modulators lead to internalization and degradation of these receptors, thereby reducing inflammation. Ozanimod was the first S1PR modulator approved for treating moderately-to-severely active UC and is also approved for multiple sclerosis. More recently, a second agent, etrasimod, was approved for UC. Etrasimod acts on different S1PR subtypes to avoid off target vascular and cardiac effects, has no up-titration regimen during initiation, a shorter half-life and less propensity for drug interactions. This review summarizes clinical trial and real-world data and provides guidance on the clinical uses of S1PR modulators.

Author Biographies

Aaron Hass, MD, Division of Gastroenterology, Department of Medicine, Centre hospitalier de l'Université de Montréal, Montreal, Canada.

Dr. Aaron Hass is a first-year gastroenterology fellow at Université de Montréal. He obtained a master’s degree in basic medical sciences at St. George’s University in Grenada. He then completed his medical school training and internal medicine residency at McGill University. He has a special interest in inflammatory bowel disease.

Laetitia Amar, MD, Division of Gastroenterology, Department of Medicine, Centre hospitalier de l'Université de Montréal, Montreal, Canada.

Dr. Amar is a first-year gastroenterology fellow at Université de Montréal. She completed her medical school training at McGill University in 2021 and internal medicine residency at the Université de Montréal in 2024.

Robert Battat, MD, FRCPC, Division of Gastroenterology, Department of Medicine, Centre hospitalier de l'Université de Montréal, Montreal, Canada.

Dr. Robert Battat, MD is an expert in inflammatory bowel disease specializing in Crohn's disease and ulcerative colitis. He is an Attending Physician and Scientist at the Centre hospitalier de l'Université de Montréal (CHUM). Dr Battat initiated his career as a clinician-scientist at Weill Cornell Medicine and he is now the director of the Centre for Clinical Excellence and Translational Research in inflammatory bowel disease (CETRI) at the Centre hospitalier de l'Université de Montréal (CHUM) in Montréal, Quebec, Canada. Dr. Battat obtained his medical degree and completed both his internal medicine residency training and clinical gastroenterology fellowship at McGill University in Montréal, Canada. He subsequently completed a clinical and research fellowship in inflammatory bowel disease at the University of California, San Diego and at Robarts Clinical Trials (Alimentiv). Dr. Battat has a major interest in multi-omics in high-risk patients with inflammatory bowel disease and has extensively published scientific articles on this topic. This includes metabolomics effects of bile acids on the microbiome and spatial transcriptomics in post-operative Crohn’s disease, therapeutic drug monitoring and pharmacokinetic interactions of biologic medicines, and multi-omic inflammatory profiles in acute severe ulcerative colitis using robust endoscopic and histologic outcomes. Dr. Battat is a reviewer for over twenty scientific journals, is on multiple editorial boards, European Crohn’s and Colitis Guidelines on Crohn’s disease and ulcerative colitis and has lectured on inflammatory bowel disease at national and international conferences. Dr. Battat has expertise in conducting clinical trials and in providing care for patients with Crohn's Disease and ulcerative colitis, ranging from those who are early in their disease to those who have been on multiple therapies or have had multiple surgeries.

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S1PR Modulators in the Management of Ulcerative Colitis: Considerations for Practice

Authors

DOI:

Abstract

Author Biographies

Aaron Hass, MD, Division of Gastroenterology, Department of Medicine, Centre hospitalier de l'Université de Montréal, Montreal, Canada.

Laetitia Amar, MD, Division of Gastroenterology, Department of Medicine, Centre hospitalier de l'Université de Montréal, Montreal, Canada.

Robert Battat, MD, FRCPC, Division of Gastroenterology, Department of Medicine, Centre hospitalier de l'Université de Montréal, Montreal, Canada.

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