Neuronal toxicity of Monoclonal antibodies (mAbs): An analysis of post marketing reports from FDA Adverse Event Reporting System (FAERS) safety database

Author:

Kumar Nitin1,Kalaiselvan Vivekanandan2,Arora Mandeep Kumar1

Affiliation:

1. School of Pharmaceutical and Population Health Informatics, DIT University, Dehradun, Uttarakhand-248 009

2. National Coordination Centre, Indian Pharmacopoeia Commission

Abstract

Abstract

Background: Monoclonal antibodies (mAbs), are pivotal in treating various diseases including cancers and autoimmune disorders. Despite their therapeutic benefits, mAbs therapy has been associated with neurological toxicity. Objectives: This study aimed to assess the incidence of neuronal toxicity associated with mAbs, utilizing data from the FDA Adverse Event Reporting System (FAERS) safety database. The study also sought to delineate the medical characteristics of the reported cases. Methods: A comprehensive analysis of neurological adverse events reported in the FAERS database was conducted, employing computational methodologies such as proportional relative risk (PRR), information component (IC025), and Chi-Square (χ2). Individual case safety reports (ICSRs) pertaining to neurological disorders linked to mAbs from the date of first global marketing authorization until June 30, 2023, were meticulously examined. Results: The FAERS safety database contains 79,022 Individual Case Safety Reports (ICSRs) linking monoclonal antibodies (mAbs) to Nervous system disorders. Rituximab, Bevacizumab, Denosumab, Nivolumab, and Trastuzumab were frequently cited. Reported adverse events include headache, peripheral neuropathy, dizziness, and cerebrovascular accident. Most ICSRs (85.81%) were serious, mainly affecting females (57.04%) with a 14.09% fatality rate. Panitumumab, Atezolizumab, Bevacizumab, and Trastuzumab showed strong drug-event associations. Signal Disproportionate Reporting (SDR) analysis flagged myasthenia gravis, peripheral neuropathy, and neurotoxicity across multiple mAbs, suggesting potential signals. Conclusions: Interdisciplinary collaboration between oncologists and neurologists is crucial for safe mAb use. Our study enhances understanding of mAb neurological safety. Disproportionality signal analysis provides valuable evidence for risk mitigation.

Publisher

Springer Science and Business Media LLC

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