Adverse events signals of enzyme replacement drugs of Gaucher disease: insights from FAERS Database analysis

Abstract

Aim: This study aims to investigate and compare the post-marketing safety profiles of three widely used enzyme replacement therapies (ERTs) for Gaucher disease—imiglucerase, velaglucerase alfa, and taliglucerase alfa. ERT involves the intravenous administration of recombinant lysosomal enzymes to compensate for the deficiency of β-glucocerebrosidase, thereby reducing the accumulation of glucocerebroside in macrophages and alleviating systemic complications. While ERT has transformed disease management, concerns about long-term adverse events persist. This analysis seeks to identify and characterize distinct safety signals associated with each agent, with a focus on disproportionality analysis rather than establishing causality. The findings aim to inform more vigilant, agent-specific clinical monitoring. Methods: Adverse event reports were extracted from the FDA Adverse Event Reporting System (FAERS) database. Disproportionality analyses were performed using the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Patient demographics, significant Preferred Terms (PTs—i.e., specific, medically-encoded adverse event descriptions), and time to onset were examined. Results: A total of 4,256 AE reports were analyzed. Our signal detection analysis identified a distinct set of statistically significant safety signals for each drug after controlling for background reporting rates. These included 37 significantly associated PTs for imiglucerase, 34 for velaglucerase alfa, and 25 for taliglucerase alfa. The safety profiles differed notably; a significant proportion of the signals for imiglucerase and velaglucerase alfa were infection-related (e.g., respiratory tract infections), whereas such signals were far less prominent for taliglucerase alfa. Unique signals included ear infection for imiglucerase, zinc deficiency for velaglucerase alfa, and hepatic fibrosis for taliglucerase alfa. The median time to onset of these signals differed significantly between agents (P<0.01). Conclusion: Long-term monitoring is essential during ERT for GD. Clinical vigilance should be heightened for infection-related complications with imiglucerase and velaglucerase alfa, while agent-specific risks like hepatic fibrosis with taliglucerase alfa warrant attention. The observed female predominance in AE reports merits further investigation. These findings are hypothesis-generating; future studies are needed to determine causality.