Reported Characteristics of Anaphylaxis Associated With Glatiramer Acetate: A Pharmacovigilance Analysis of the FDA and Canadian Databases.

Abstract

The FDA has mandated a Boxed Warning for glatiramer acetate (GA) due to the risk of serious anaphylactic reaction. This study aimed to characterize the reported features of GA-associated anaphylaxis. Data mining was performed using the Reporting Odds Ratio (ROR) in the FDA Adverse Event Reporting System (FAERS) database (Q1 2004-Q1 2025) and the Canadian Vigilance Adverse Reaction (CVAR) database (Q1 1996-Q1 2025). Demographic characteristics, time-to-onset (TTO), and case seriousness were compared using the Mann-Whitney U test or the Chi-squared (χ²) test. In the FAERS database, 9816 reports were identified with 29 significant disproportionality signals. Younger age (p < 0.01) was significantly associated with a higher proportion of serious reports. The association between GA and anaphylactic AEs remained statistically significant after stratification by age, body weight, sex, and reporter types. Twenty AEs demonstrated significantly higher reporting rates in serious cases (p < 0.05). Clinical prioritization identified 9 moderate-priority and 20 weak-priority signals. The median TTO was 197 days for moderate-priority signals versus 153 days for weak-priority signals. All signals exhibited early failure-type patterns, indicating that reported anaphylactic events were more frequently observed earlier after treatment initiation than later in treatment. In the CVAR database, 711 reports were identified. A total of 17 PTs overlapped with FAERS, with respiratory arrest uniquely present in CVAR. Three PTs were rated as moderate priority in the CVAR database but weak priority in FAERS. This large-scale pharmacovigilance analysis of the FDA and Canadian databases characterizes the safety signals derived from GA-associated reports of anaphylaxis, providing a hypothesis-generating foundation for future pharmacovigilance validation.