Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan.
School of Pharmacy, Hyogo Medical University, Kobe, Japan.
Oncology. 2023;101(10):664-674. doi: 10.1159/000531390. Epub 2023 Jun 6.
Azacitidine is a useful drug for myelodysplastic syndromes and acute myeloid leukemia. In clinical trials, hematologic toxicity and infection have been observed as adverse events (AEs) of this drug. However, information on the time to onset of high risk AEs and subsequent outcomes, as well as differences in the frequency of AEs due to the route of administration is lacking. In this study, we investigated azacitidine-induced AEs comprehensively using the Japanese Adverse Event Reporting Database (JADER) published by the Pharmaceuticals and Medical Devices Agency, with disproportionate analysis of AE incidence trends, time to onset, and subsequent outcomes. In addition, we analyzed the differences in AEs by route of administration and the number of days until the occurrence of AEs and generated hypotheses.
The study used JADER data reported from April 2004 to June 2022. Risk estimation was conducted using reported odds ratio. A signal was detected when the lower limit of the 95% confidence interval of the calculated ROR was ≥1.
A total of 34 signals were detected as AEs due to azacitidine. Among them, 15 were hematologic toxicities and 10 were infections, which demonstrated a particularly high rate of death. Signals of AEs such as tumor lysis syndrome (TLS) and cardiac failure, which have been described in case reports, were also detected, and the rate of death after onset was high. In addition, more AEs generally occurred within the first month of treatment.
The results of this study suggest that more attention should be paid to cardiac failure, hematologic toxicity, infection, and TLS. Because many patients in clinical trials have discontinued treatment due to serious AEs before the therapeutic effect became apparent, appropriate supportive care, dose reduction, and drug withdrawal are important for the continuation of treatment.
阿扎胞苷是一种用于骨髓增生异常综合征和急性髓系白血病的有效药物。在临床试验中，血液学毒性和感染已被观察为该药物的不良事件（AE）。然而，缺乏关于高危 AE 发作时间和随后结果的信息，以及由于给药途径不同导致的 AE 频率差异的信息。在这项研究中，我们使用日本药品和医疗器械局（PMDA）发布的日本不良事件报告数据库（JADER）全面研究了阿扎胞苷引起的 AE，对 AE 发生率趋势、发作时间和随后结果进行了不均衡分析。此外，我们还分析了给药途径和 AE 发生前天数的差异，并提出了假设。
该研究使用了 2004 年 4 月至 2022 年 6 月报告的 JADER 数据。使用报告的比值比进行风险估计。当计算出的 ROR 的 95%置信区间的下限≥1 时，会检测到信号。
共检测到 34 个与阿扎胞苷相关的 AE 信号。其中，15 个为血液学毒性，10 个为感染，死亡率特别高。还检测到肿瘤溶解综合征（TLS）和心力衰竭等 AE 的信号，这些信号在病例报告中已有描述，发病后死亡率也很高。此外，大多数 AE 通常在治疗的第一个月内发生。
本研究结果表明，应更加关注心力衰竭、血液学毒性、感染和 TLS。由于许多临床试验中的患者在治疗效果明显之前因严重 AE 而停止治疗，因此适当的支持性护理、剂量减少和药物停药对于治疗的持续进行很重要。
