Evaluation and study of adverse reactions to imiglucerase based on the FAERS database

Abstract

Objective: This study aims to evaluate the adverse drug reactions associated with imiglucerase in the treatment of Gaucher disease by analyzing data from the FDA Adverse Event Reporting System (FAERS) database.

Methods: A comprehensive analysis was conducted on 166,800,135 adverse event reports from the FAERS database, covering the period from the first quarter of 2004 to the fourth quarter of 2023. The data were processed using R software and analyzed using multiple disproportionality methods, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS). These methodologies were applied to identify significant adverse reaction signals across various System Organ Classes (SOCs) and Preferred Terms (PTs).

Results: The analysis revealed significant adverse reaction signals in multiple SOCs, including general disorders and administration site conditions, injury, poisoning and procedural complications, infections and infestations, and nervous system disorders. Notably, general disorders and injury-related conditions had the highest number of reports. At the PT level, the term "Gaucher disease" yielded the highest statistical signal. This was identified as a critical reporting artifact, likely representing perceived treatment failure or disease progression, rather than a true adverse reaction. After accounting for this artifact, other significant adverse event signals included increased chitotriosidase, elevated acid phosphatase, and bone infarction, with musculoskeletal and connective tissue disorders being a key area of concern. A comparative analysis against other Gaucher therapies suggests this strong skeletal signal likely reflects confounding by indication rather than a drug-specific risk.

Conclusion: The findings underscore the importance of ongoing pharmacovigilance to monitor the safety of imiglucerase, especially among vulnerable populations such as pregnant women, long-term users, and those with comorbid hepatobiliary or skeletal conditions.

Keywords: Adverse drug reactions; FAERS database; Gaucher disease; Imiglucerase; Pharmacovigilance.

Fig. 1

Flowchart depicting the selection process of imiglucerase-related adverse events (AEs) from the FAERS database

Fig. 2

Annual and quarterly distribution of adverse event reports (AERs) Related to Imiglucerase from FAERS Database

Fig. 3

Waterfall plot of the top adverse event signals for imiglucerase ranked by signal strength. Each bar represents a unique adverse event term (Preferred Term), ranked by its Information Component (IC) value on the y-axis. The error bars indicate the 95% confidence interval for the IC estimate. The color gradient corresponds to the number of case reports for each term, and the horizontal dashed line at IC = 0 represents the threshold for signal detection