School of Pharmaceutical and Population Health Informatics, DIT University, Dehradun, Uttarakhand, 248 009, India.
Pharmacovigilance Programme of India (PvPI), National Coordination Centre, Indian Pharmacopoeia Commission, Uttar Pradesh, Ghaziabad, India.
Eur J Clin Pharmacol. 2024 Nov;80(11):1685-1695. doi: 10.1007/s00228-024-03727-0. Epub 2024 Jul 25.
Monoclonal antibodies (mAbs) are pivotal in treating various diseases, including cancers and autoimmune disorders. Despite their therapeutic benefits, mAb therapy has been associated with neurological toxicity.
This study aimed to assess the occurrence 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.
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 (IC), and chi-square (χ). 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.
The FAERS safety database contains 79,022 ICSRs linking 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.
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.
单克隆抗体（mAbs）在治疗各种疾病方面发挥着关键作用，包括癌症和自身免疫性疾病。尽管 mAb 疗法具有治疗益处，但它与神经毒性有关。
本研究旨在利用 FDA 不良事件报告系统（FAERS）安全性数据库中的数据，评估与 mAb 相关的神经元毒性的发生情况。该研究还旨在描述报告病例的医学特征。
对 FAERS 数据库中报告的神经系统不良事件进行了全面分析，采用了比例相对风险（PRR）、信息成分（IC）和卡方（χ）等计算方法。详细检查了自首次全球营销授权之日起至 2023 年 6 月 30 日与 mAb 相关的神经障碍的 FAERS 数据库中涉及的单个病例安全报告（ICSR）。
FAERS 安全性数据库包含 79022 份将 mAb 与神经系统疾病联系起来的 ICSR。利妥昔单抗、贝伐珠单抗、地舒单抗、纳武利尤单抗和曲妥珠单抗经常被提及。报告的不良事件包括头痛、周围神经病、头晕和脑血管意外。大多数 ICSR（85.81%）是严重的，主要影响女性（57.04%），死亡率为 14.09%。帕尼单抗、阿替利珠单抗、贝伐珠单抗和曲妥珠单抗显示出与药物相关的强烈关联。信号不均衡报告（SDR）分析标记了多种 mAb 的重症肌无力、周围神经病和神经毒性，表明存在潜在信号。
肿瘤学家和神经学家之间的跨学科合作对于 mAb 的安全使用至关重要。我们的研究增强了对 mAb 神经安全性的理解。不均衡性信号分析为风险缓解提供了有价值的证据。
