Zhang Xia, Liu Yuyu, Hou Qingwang, Guo Yongxin, He Youfu
Department of Oncology, Guihang Guiyang Hospital, Guiyang, Guizhou, China.
School of Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Front Pharmacol. 2025 Jan 14;15:1527903. doi: 10.3389/fphar.2024.1527903. eCollection 2024.
DNA methylation inhibitors have been approved for the prevention of Acute Myeloid Leukemia (AML), and their safety profile is not fully characterized. This study was aimed at evaluating the adverse drug reactions (ADRs) of DNA methylation inhibitors by analyzing the individual case safety reports (ICSRs) collected in the EudraVigilance (EV) database.
The EV database managed by the European Medicines Agency was adopted. The standardized medical terminology set MedDRA was utilized. The ICSRs data of DNA methylation inhibitors for the treatment of acute myeloid leukemia originated from the EV database (2005-2024). A descriptive exploration of the combined data from EV was undertaken to assess the age, gender of patients, severity and outcome of ADR, event year, geographical origin and the qualification of the reporting source. A comprehensive assessment was made for severe ADR cases. By means of the Reporting Odds Ratio (ROR) and 95% Confidence Interval (CI), a non-proportional analysis was made for MedDRA SOC in DNA methylation inhibitors. Statistical analysis was executed with SPSS version 23.0, and < 0.05 was regarded as statistically significant.
The study reveals that reports related to AZACITIDINE increased from 2005 to 2023, with a slight decline in 2024, while those for DECITABINE have been on the rise since 2007. ICSRs were associated with a majority of males and individuals aged 65-85. Healthcare professionals frequently reported ICSRs related to DNA methylation inhibitors. A significant portion of these ICSRs were serious and completely resolved. The most common ADRs were identified, and certain ADRs had a higher reporting probability with AZACITIDINE (e.g., Febrile neutropenia, Anamia, etc.) and others with DECITABINE (e.g., Myelosuppression, Thrombocytopenia, etc.).
The analysis regarding ADRs of DNA methylation inhibitors was consistent with the literature information disclosed. AZACITIDINE and DECITABINE each have ADRs with a high probability of being reported. Although the study has the advantage of using the database, it is limited by the spontaneous reporting system. Future improvements are needed to accurately evaluate the safety of the drugs.
DNA甲基化抑制剂已被批准用于预防急性髓系白血病（AML），但其安全性尚未完全明确。本研究旨在通过分析欧洲药品管理局药物警戒数据库（EudraVigilance，EV）中收集的个体病例安全报告（ICSR）来评估DNA甲基化抑制剂的药物不良反应（ADR）。
采用欧洲药品管理局管理的EV数据库。使用标准化医学术语集MedDRA。治疗急性髓系白血病的DNA甲基化抑制剂的ICSR数据源自EV数据库（2005 - 2024年）。对来自EV的合并数据进行描述性探索，以评估患者的年龄、性别、ADR的严重程度和转归、事件年份、地理来源以及报告来源的资质。对严重ADR病例进行全面评估。通过报告比值比（ROR）和95%置信区间（CI），对DNA甲基化抑制剂中的MedDRA系统器官分类（SOC）进行非比例分析。使用SPSS 23.0版本进行统计分析，P < 0.05被视为具有统计学意义。
研究显示，与阿扎胞苷相关的报告从2005年至2023年呈上升趋势，2024年略有下降，而地西他滨相关报告自2007年以来一直在增加。ICSR与大多数男性以及65 - 85岁的个体相关。医疗保健专业人员经常报告与DNA甲基化抑制剂相关的ICSR。这些ICSR中有很大一部分是严重的且已完全缓解。确定了最常见的ADR，某些ADR在阿扎胞苷治疗时报告概率较高（如发热性中性粒细胞减少、贫血等），而其他ADR在地西他滨治疗时报告概率较高（如骨髓抑制、血小板减少等）。
关于DNA甲基化抑制剂ADR的分析与已公开的文献信息一致。阿扎胞苷和地西他滨各自都有报告概率较高的ADR。尽管本研究具有使用数据库的优势，但受自发报告系统的限制。未来需要改进以准确评估这些药物的安全性。
