Correlation between erythropoiesis-stimulating agents and seizures: a study based on Mendelian randomization and the FAERS database
10.3760/cma.j.cn114015-20241021-00109
- VernacularTitle:红细胞生成刺激剂与癫痫的关联性：基于孟德尔随机化和FAERS数据库的研究
- Author:
Cuilyu LIANG
1
;
Peihong WANG
1
Author Information
1. 福建医科大学附属第二医院药学部，泉州 362000
- Publication Type:Journal Article
- Keywords:
Erythropoietin;
Seizures;
Causality;
Mendelian randomization analysis;
Pharmacovigilance;
Adverse drug reaction reporting systems
- From:
Adverse Drug Reactions Journal
2025;27(10):592-599
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the correlation between erythropoiesis-stimulating agents (ESAs) and seizures.Methods:Drug target Mendelian randomization (MR) and multivariate MR analysis were employed to evaluate the causal correlation between ESAs and seizures as well as status epilepticus. The data were sourced from published genome-wide association studies (GWAS) in the UK Biobank and Finland FinnGen databases. The instrumental variables were ESA-related single-nucleotide polymorphisms (SNPs) with F>10, the exposure factor was ESAs treatment, and outcome measures were seizures and status epilepticus. The methods of inverse variance weighted (IVW), weighted median estimator (WME) and MR-Egger regression were applied in the drug-target MR analysis, and the methods of IVW, MR-Egger regression and MR-LASSO were applied in the multivariate MR analysis. Adverse event reports from January 2004 to June 2024 in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database were collected. The signals of ESA-related seizures and status epilepticus were detected by reporting odds ratio (ROR) method and proportional reporting ratio (PRR) method. Results:A total of 15 SNPs were included in the MR analysis. Drug-target MR analysis showed that ESAs were significantly associated with the risk of seizures [IVW odds ratio ( OR)=1.575, 95% confidence interval ( CI): 1.055-2.353, P=0.026], but not associated with the risk of status epilepticus ( OR=1.818, 95 %CI: 0.403-8.207, P=0.437). Multivariate MR analysis showed that the above significant association was not found after correcting the risk factors of seizures such as stroke, pulmonary embolism, brain tumor, and dementia ( OR=0.359, 95 %CI: -0.014- 0.732, P=0.059). No risk signals of seizures and status epilepticus caused by 3 ESAs (recombinant human erythropoietin, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta) were detected in FAERS database. Conclusion:ESAs may not lead to an increase in risk of seizures.
