A disproportionality analysis of adverse event reports for givinostat in the FDA adverse event reporting system (FAERS) database
Abstract
Givinostat was recently approved for Duchenne muscular dystrophy (DMD), but its real-world safety profile remains incompletely characterized. We evaluated givinostat-associated safety signals by data mining of the FDA Adverse Event Reporting System (FAERS) database. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) were applied to 321 reports with givinostat as the primary suspect (PS) drug from Q1 2024 to Q1 2026. A likelihood ratio test (LRT) with Benjamini–Hochberg (BH) correction further assessed whether specific adverse events (AEs) were disproportionately associated with serious outcomes. Serious versus non-serious cases were compared by logistic regression and univariate tests. At the system organ class (SOC) level, investigations (ROR 5.54), gastrointestinal disorders (ROR 4.09), and blood and lymphatic system disorders (ROR 3.43) showed the strongest signals. For the preferred term (PT) level, blood triglycerides exhibited the strongest signal (ROR 341.3), while platelet count decreased was the most frequently reported ( n = 96, 29.9%). After BH adjustment, platelet count decreased was the only PT with a significantly lower serious proportion than the overall baseline (14.58% vs. 30.07%, adjusted p = 0.024). Time-to-Onset (TTO) Analysis showed that diarrhoea typically occurred within the first week, whereas platelet count decreased and thrombocytopenia had delayed median onset (15.5 days and 17 days, respectively). Our study identified thrombocytopenia and hypertriglyceridemia as the most prominent safety signals for givinostat, with platelet count decreased showing a statistically significant difference in serious proportion and a lower serious proportion than the overall baseline. These findings provide evidence-based targets for structured hematological and metabolic monitoring, particularly during the early treatment phase, to support risk management in DMD patients receiving givinostat.