Disproportionality analysis of adverse events associated with asfotase alfa: a post-marketing study using the FDA Adverse Event Reporting System.

Abstract

Background: Asfotase alfa (AA) is an FDA-approved enzyme replacement therapy for hypophosphatasia (HPP). Limited real-world data on its adverse events (AEs) exist. This study evaluates AA-related AEs using the U.S. FDA's Adverse Event Reporting System (FAERS) database.

Methods: Reports for AA were extracted from FAERS and analyzed per FDA guidelines. AEs were categorized using MedDRA version 26.1. Disproportionality analysis was conducted using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM) algorithms. Time-to-onset (TTO) was calculated, with a Weibull shape parameter test to assess risk over time.

Results: Out of 13,702,373 reports, 5,040 AA-related AEs were identified, with 198 significant preferred terms (PTs). Common AEs included injection site reactions and pain, with additional PTs for ear/labyrinth disorders and infections. The median onset for 234 AEs with reported times was 170 days (IQR 18-390 days). No significant differences in AEs were found across gender or age groups.

Conclusion: Most AEs align with known data, but newly identified ear/labyrinth disorders and infections require further investigation to enhance AA's safety profile.