Comprehensive Analysis of Ozanimod-Related Adverse Events Based on the FAERS Database

Abstract

Background: Ozanimod, a selective sphingosine-1-phosphate receptor modulator, has been approved for the treatment of moderately to severely active ulcerative colitis (UC) and relapsing forms of multiple sclerosis (MS). However, its postmarketing adverse event (AE) reporting profile requires further characterization.

Methods: AE reports involving ozanimod from Q2 2020 to Q1 2025 were retrieved from the FDA Adverse Event Reporting System (FAERS) database. Frequency-based and Bayesian disproportionality methods were applied, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM), to identify pharmacovigilance reporting signals.

Results: A total of 15,910 AE reports involving ozanimod were retrieved, of which 7,305 reports listed ozanimod as the primary suspected drug. Most reports involved patients aged 18–64 years (67.5%), and more reports were submitted for female patients than for male patients. Frequently reported events included fatigue, headache, dizziness, and back pain. Labeled or clinically recognized safety events, such as decreased lymphocyte count, decreased heart rate, hypertension, macular edema, and liver test abnormalities, were also detected as reporting signals. Disease-related Preferred Terms, including MS relapse, MS, UC, and proctitis ulcerative, showed strong disproportionality signals but may reflect underlying disease activity, treatment failure, indication, or reporting context rather than toxic adverse drug reactions. In addition, several hypothesis-generating FAERS signals not explicitly listed in current product labeling were observed, including depression, feeling of despair, decreased interest, penile swelling, and papillary thyroid cancer. These findings require cautious interpretation because FAERS cannot establish incidence, absolute risk, or causality.

Conclusions: This study provides a postmarketing pharmacovigilance signal profile of AE reports involving ozanimod. The findings support continued monitoring of labeled safety concerns, careful interpretation of disease-activity-related reports, and further validation of selected unlabeled signals in prospective studies or better-controlled real-world datasets.