Chen Shupeng, Liu Jie, Gao Yao, Tang Nana, Zeng Yingjian
School of Clinical Medicine, Jiangxi University of Chinese Medicine, Nanchang, China,
School of Clinical Medicine, Jiangxi University of Chinese Medicine, Nanchang, China.
Oncology. 2025 Jan 30:1-18. doi: 10.1159/000543519.
The real-world safety profiles of the demethylating agents azacitidine and decitabine remain inadequately characterized despite their widespread clinical use. Both drugs are extensively employed for the treatment of hematologic malignancies such as myelodysplastic syndromes and acute myeloid leukemia. This study aimed to evaluate their adverse event profiles by leveraging data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database.
All adverse drug event (ADE) data related to azacitidine and decitabine were collected from the FAERS database from its inception through the second quarter of 2024 (Q2). After standardizing the data, four disproportionality methods were applied to evaluate the association between azacitidine, decitabine, and ADEs. The Weibull shape parameter was used to analyze the time-to-onset curves.
Among the 15,538 ADEs where azacitidine was the primary suspect drug, a total of 439 preferred terms (PTs) and 2 system organ classes (SOCs) showed significant disproportionality across all four algorithms. These SOCs included infections and infestations (n = 7,328, ROR 3.78) and blood and lymphatic system disorders (n = 5,613, ROR 8.92). Compared with the azacitidine label, 52 previously unreported ADEs were identified at the PT level. Among the 3,064 ADEs where decitabine was the primary suspect drug, a total of 200 PTs and two SOCs exhibited significant disproportionality across all four algorithms. These SOCs included blood and lymphatic system disorders (n = 1,284, ROR 6.53) and surgical and medical procedures (n = 571, ROR 3.41). Compared with the decitabine label, 29 previously unreported ADEs were identified at the PT level. Furthermore, the Bayesian Confidence Propagation Neural Network (BCPNN) algorithm revealed that the highest IC025 values for both azacitidine and decitabine were concentrated in SOCs related to benign, malignant, and unspecified tumors.
In summary, using the FAERS database, we compared the real-world safety profiles of two demethylating agents, azacitidine and decitabine. The results indicate that adverse drug reactions related to these two agents are concentrated in the hematologic, respiratory, circulatory, and digestive systems, as well as in neoplasms of unspecified nature, warranting close clinical attention.
尽管去甲基化药物阿扎胞苷和地西他滨在临床中广泛应用，但其真实世界的安全性特征仍未得到充分描述。这两种药物都被广泛用于治疗血液系统恶性肿瘤，如骨髓增生异常综合征和急性髓系白血病。本研究旨在利用美国食品药品监督管理局（FDA）不良事件报告系统（FAERS）数据库的数据评估它们的不良事件特征。
从FAERS数据库建立之初至2024年第二季度（Q2），收集所有与阿扎胞苷和地西他滨相关的药物不良事件（ADE）数据。在对数据进行标准化处理后，应用四种不成比例分析方法评估阿扎胞苷、地西他滨与ADE之间的关联。使用威布尔形状参数分析发病时间曲线。
在以阿扎胞苷为主要可疑药物的15538例ADE中，共有439个首选术语（PT）和2个系统器官类别（SOC）在所有四种算法中均显示出显著的不成比例性。这些SOC包括感染和侵染（n = 7328，报告比值比3.78）以及血液和淋巴系统疾病（n = 5613，报告比值比8.92）。与阿扎胞苷标签相比，在PT水平上识别出52例先前未报告的ADE。在以地西他滨为主要可疑药物的3064例ADE中，共有200个PT和两个SOC在所有四种算法中均表现出显著的不成比例性。这些SOC包括血液和淋巴系统疾病（n = 1284，报告比值比6.53）以及外科和医疗程序（n = 571，报告比值比3.41）。与地西他滨标签相比，在PT水平上识别出29例先前未报告的ADE。此外，贝叶斯置信传播神经网络（BCPNN）算法显示，阿扎胞苷和地西他滨的最高IC025值都集中在与良性、恶性和未指定肿瘤相关的SOC中。
总之，我们利用FAERS数据库比较了两种去甲基化药物阿扎胞苷和地西他滨的真实世界安全性特征。结果表明，与这两种药物相关的药物不良反应集中在血液、呼吸、循环和消化系统以及性质未明的肿瘤中，值得临床密切关注。
