Risk signal mining and analysis of adverse events in agalsidase beta therapy for Fabry disease
10.3760/cma.j.cn114015-20250417-00206
- VernacularTitle:阿加糖酶β在治疗法布雷病中的不良事件信号挖掘与分析
- Author:
Zongyun LI
1
;
Jiaxun JIAO
;
Lingna GAO
;
Xiaoli ZHU
Author Information
1. 河北省衡水市人民医院临床药学科，衡水 053000
- Publication Type:Journal Article
- Keywords:
Enzyme replacement therapy;
X chromosome;
Genes, recessive;
Fabry disease;
Agalsidase beta;
Adverse events;
Data mining
- From:
Adverse Drug Reactions Journal
2025;27(11):686-693
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To mine risk signals of adverse events (AE) in agalsidase beta therapy for Fabry disease and provide reference for the safe use in clinical practice.Methods:The AE reports with agalsidase beta as the primary suspect drug in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the third quarter of 2024 were collected and the clinical information of patients involved was analyzed descriptively. AEs were standardized and categorized using the preferred term (PT) and system organ class (SOC) in Medical Dictionary for Regulatory Activities version 26.0. Signal mining was performed using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. A PT was defined as the risk signal if the number of reports was ≥3, the lower limit of the 95% confidence interval ( CI) of ROR was >1, and the information component minus two times standard deviation ( IC025) was >0. Descriptive statistical analysis were then conducted on the risk signals. The relative risk of target adverse events in gender subgroups was evaluated using the ROR method. Results:A total of 24 163 AE reports with agalsidase beta as the primary suspect drug were collected, involving 7 763 patients and 2 382 PTs. Severe adverse events accounted for 34.9% (2 712/7 763). A total of 121 risk signals (namely PTs) across 15 SOCs were obtained. The top 5 PTs ranked by number of reports were pyrexia (483 cases), chills (449 cases), infusion related reaction (282 cases), chest pain (221 cases), and cerebrovascular accident (218 cases). The top 5 PTs ranked by signal intensity were cornea verticillata ( ROR=56.44, IC025=4.59), drug specific antibody present ( ROR=54.13, IC025=5.46), cerebral calcification ( ROR=24.82, IC025=3.16), myocardial necrosis marker increased ( ROR=24.14, IC025=3.83), and infusion site rash ( ROR=20.41, IC025=3.46). Among the top 30 PTs ranked by number of reports and signal intensity, there were 4 and 13 PTs not documented in the drug label, respectively. The former included atrial fibrillation, cellulitis, neuralgia, and pallor, while the latter included cornea verticillate, cerebral calcification, auricular swelling, vein discoloration, aortic dilatation, bundle branch block, myocardial fibrosis, cardiac infection, vein rupture, sudden hearing loss, meningitis viral, deafness transitory, and corneal opacity. Subgroup analysis by sex showed that males had higher risks in developing chills, tremor, drug specific antibody detection, renal failure, and renal impairment, while females had higher risks in weight increase and dizziness. Conclusions:The main risk signals of adverse events of agalsidase beta include pyrexia, chills, and infusion related reactions, which are consistent with those documented in package inserts. In addition, potential new risk signals such as atrial fibrillation, cellulitis, neuralgia, cornea verticillate, auricular swelling, and sudden hearing loss were also detected. The relative risks of some target adverse events vary between genders, and it is recommended to strengthen targeted drug monitoring and individualized management in clinical practice.
