Efficacy and Safety of S1P1 Receptor Modulator Drugs for Patients with Moderate-to-Severe Ulcerative Colitis

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that negatively impacts patients’ quality of life. In the last decades, the therapeutic options available for the management of patients with moderate to severe UC have increased significantly, including not only biological drugs but also small molecules. However, there is a persistent need to develop new drugs that act on new targets while minimizing the risk of adverse events. Sphingosine-1-phosphate (S1P) is a membrane-derived lysophospholipid. The S1P gradient between tissues and the circulatory system has a key role in regulating the trafficking of immune cells as autoreactive B and T lymphocytes. S1P receptor modulators could be a safe and efficacious alternative mechanism for reducing inflammation in immune-mediated disorders, including UC, by reducing lymphocyte egress from the lymph nodes to the bloodstream. Several S1P receptor modulators have been developed and tested in UC. Ozanimod is already approved by Food and Drug Administration (FDA) and European Medical Agency (EMA), while etrasimod and VTX002 are still under approval. Oral administration route, rapidity and reliable safety profile are the main advantages of this class of drugs. The aim of this review is to summarize the available evidence for the efficacy, safety, and pharmacokinetics of ozanimod, etrasimod, and VTX002 in UC.

Selecting first-line advanced therapy for ulcerative colitis: A clinical application of personalized medicine

“…[ 44 ] Similarly, S1P1 inhibitors have been associated with infection risk, macular edema, and arrhythmias. [ 35 ] In comparison, SLAMI[ 45 ] and anti-cytokines[ 46 ] have favorable safety profiles and seem to be the most rational first choice when the start of advanced therapy is decided in this age group.…”

“…S1P1 inhibitors are associated with an increased risk of infection, hepatotoxicity, and cardiotoxicity. [ 35 ] Currently, among the class of S1P1 inhibitors, only ozanimod has been approved for treating UC. [ 35 ] Etrasimod is another S1P1 inhibitor in the final stages of approval for treating UC [ Table 1 ].…”

“…[ 35 ] Currently, among the class of S1P1 inhibitors, only ozanimod has been approved for treating UC. [ 35 ] Etrasimod is another S1P1 inhibitor in the final stages of approval for treating UC [ Table 1 ]. [ 36 ]…”

Ozanimod Differentially Impacts Circulating Lymphocyte Subsets in Patients with Moderately to Severely Active Crohn’s Disease

“…Other types of lymphocytes, such as B cells and natural killer (NK) cells, are also involved in the pathogenesis of IBD [ 3 , 6 ]. Accordingly, blocking the egress of lymphocytes from lymphoid tissues into the bloodstream is an established therapeutic approach with proven efficacy and safety in IBD [ 7 ].…”

Extracellular Vesicles: Novel Potential Therapeutic Agents in Inflammatory Bowel Diseases

“…In cases of moderate or severe disease, IBD physicians can rely on anti-tumor necrosis factor alfa (anti-TNFα), anti-integrins, anti-interleukin 23 (anti-IL23), and Janus kinase inhibitors (anti-JAK) [ 10 , 11 ]. New drugs, such as anti-sphingosine 1 phosphate (anti-S1P), have more recently appeared in the IBD landscape, and several clinical trials are currently testing different molecules [ 12 ].…”