Exploring adverse events associated with sphingosine-1-phosphate modulators: a pharmacovigilance study using the FDA Adverse Event Reporting System Database

Abstract

Abstract Background Sphingosine-1-phosphate receptor (S1PR) modulators have been proposed as therapeutic agents for various diseases. However, the presence of S1PR in multiple tissues may lead to numerous off-target effects of S1PR modulators, potentially limiting their use. There are no real-world reports on adverse effects of S1PR modulators. Aim This study aimed to investigate post-marketing adverse event (AE) of S1PR modulators, and to explore risk factors for severe AE. Method Disproportionality analyses were performed on adverse event cases of S1PR modulators (2004-2022) collected from the US Food and Drug Administration Adverse Event Reporting System (FAERS). Risk prediction model was developed for severe AE of S1PR modulators using logistic regression analyses. Results A total of 95,577 AE reports were retrieved. The prominent risk signals of the S1PR modulators were fatigue, relapses in multiple sclerosis, and headaches. Age, thyroid preparations, and monoclonal antibodies were independent risk factors for severe AE (p < 0.05). The risk prediction model for severe AE and the corresponding nomogram exhibited discrimination ability and clinical applicability in both training set (AUC 0.6102) and validation sets (AUC 0.6079). Conclusion Our post-marketing pharmacovigilance analysis revealed the types and incidence of AE related to S1PR modulators. The nomogram may be useful for rapid clinical assessment on the occurrence of severe AE.