Wu Shanshan, Huang Lina, Chen Jiajia, Xie Xiaochun, Huang Shaokai, Huang Xiaojie
Department of Clinical Pharmacy, Jieyang People's Hospital, Jieyang, China.
Front Pharmacol. 2025 Mar 5;16:1525307. doi: 10.3389/fphar.2025.1525307. eCollection 2025.
Non-chemotherapy drug-induced agranulocytosis (NCDIA) is a serious adverse reaction that significantly increases the risk of life-threatening infections. Although the association between certain non-chemotherapy drugs and agranulocytosis has been documented, a comprehensive analysis using a large-scale pharmacovigilance database is lacking. This study aimed to systematically identify and characterize NCDIA by analyzing adverse event reports from the FAERS database.
We conducted a retrospective analysis of NCDIA reports from the FAERS database spanning from 2004 to 2024 Q1. Drugs were classified using the Anatomical Therapeutic Chemical (ATC) classification system, with chemotherapy agents (ATC code L01) excluded. The Reporting Odds Ratio (ROR) method was employed to detect potential adverse event signals. Positive signals were defined as cases with at least three reports and a lower 95% confidence interval (CI) of ROR greater than one. Time-to-event analysis was also performed to examine onset patterns across different demographic groups and drugs.
A total of 10,913 NCDIA reports were identified from the FAERS database. Disproportionality analysis revealed significant signals for 166 non-chemotherapy drugs related to agranulocytosis, which were systematically classified into three risk categories: known (n = 111), possible (n = 25), and new potential risks (n = 30). This classification system enables us to identify drugs with known risks, those that might pose a risk, and new risks warranting further investigation. Demographic analysis revealed that females, children (<18 years), and the elderly (≥65 years) experienced earlier onset of agranulocytosis. Drug-specific onset timing analysis provided evidence for optimizing monitoring protocols. Notably, NCDIA-associated mortality rates showed a significant decrease from 11.91% (2004-2010) to 7.28% (2021-2024) ( < 0.001).
This comprehensive pharmacovigilance study not only confirmed previously known NCDIA associations but also identified new potential risk drugs. The novel risk classification system and detailed onset timing analysis provide valuable insights for clinical monitoring. The findings of earlier onset in specific populations and declining mortality trends have important implications for developing targeted surveillance strategies and improving patient safety management.
非化疗药物引起的粒细胞缺乏症（NCDIA）是一种严重的不良反应，会显著增加危及生命感染的风险。尽管某些非化疗药物与粒细胞缺乏症之间的关联已有文献记载，但缺乏使用大规模药物警戒数据库进行的综合分析。本研究旨在通过分析来自FDA不良事件报告系统（FAERS）数据库的不良事件报告，系统地识别和描述NCDIA。
我们对FAERS数据库中2004年至2024年第一季度的NCDIA报告进行了回顾性分析。使用解剖学治疗学化学（ATC）分类系统对药物进行分类，排除化疗药物（ATC代码L01）。采用报告比值比（ROR）方法检测潜在的不良事件信号。阳性信号定义为至少有三份报告且ROR的95%置信区间下限大于1的病例。还进行了事件发生时间分析，以研究不同人口统计学群体和药物的发病模式。
从FAERS数据库中总共识别出10913份NCDIA报告。不成比例分析揭示了166种与粒细胞缺乏症相关的非化疗药物的显著信号，这些药物被系统地分为三类风险：已知风险（n = 111）、可能风险（n = 25）和新的潜在风险（n = 30）。这种分类系统使我们能够识别具有已知风险的药物、可能构成风险的药物以及需要进一步调查的新风险。人口统计学分析表明，女性、儿童（<18岁）和老年人（≥65岁）粒细胞缺乏症的发病时间较早。药物特异性发病时间分析为优化监测方案提供了证据。值得注意的是，NCDIA相关死亡率从2004 - 2010年的11.91%显著下降至2021 - 2024年的7.28%（<0.001）。
这项全面的药物警戒研究不仅证实了先前已知的NCDIA关联，还识别出了新的潜在风险药物。新颖的风险分类系统和详细的发病时间分析为临床监测提供了有价值的见解。特定人群发病较早和死亡率下降趋势的研究结果对于制定有针对性的监测策略和改善患者安全管理具有重要意义。
