Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan.
Department of Education and Research Center for Pharmacy Practice, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyotanabe, Japan.
Oncology. 2022;100(7):413-418. doi: 10.1159/000524806. Epub 2022 May 3.
Ixazomib is an orally available proteasome inhibitor for multiple myeloma with adverse effects such as gastrointestinal symptoms, skin rashes, and thrombocytopenia reported in clinical trials and post-marketing surveillance, resulting in treatment discontinuation. However, comprehensive adverse event (AE) assessments for ixazomib are lacking.
Herein, we aimed to determine the frequency and risk of AEs associated with ixazomib in Japanese patients using the Japanese Adverse Event Reporting Database (JADER). Additionally, the time to onset and post hoc outcomes of unique AEs were clarified.
To investigate the association between ixazomib and AEs, we analyzed the JADER database, comprising voluntary AE reports submitted to the Pharmaceuticals and Medical Devices Agency, between April 2004 and June 2021. AEs with ≥10 reports were included in the analysis, and criteria for the presence of AE signals were defined as meeting the requirements of proportional report ratio ≥2 and χ2 ≥ 4. Characteristic AEs were analyzed considering time to onset and onset outcomes.
Of 34 extracted AEs, 18 presented AE signals. The 12 post hoc outcomes with fatality rates ≥10% included septic shock (50.0%), infection (41.2%), heart failure (16.7%), pneumonia (14.2%), and tumor necrosis syndrome (13.3%). A median of the time to onset showed that 11 of the 18 AEs occurred from ixazomib initiation to approximately 1 month later.
Our results suggest that ixazomib may increase the incidence of 18 AEs, 11 of which occurred within the first month of treatment. Furthermore, 8 AEs were found to have potentially fatal outcomes at a rate of ≥10%. Therefore, monitoring AEs during the first month of treatment appears necessary.
伊沙佐米是一种口服蛋白酶体抑制剂，用于多发性骨髓瘤，临床试验和上市后监测中报告了胃肠道症状、皮疹和血小板减少等不良反应，导致治疗中断。然而，目前缺乏对伊沙佐米全面不良事件（AE）评估。
本研究旨在使用日本不良事件报告数据库（JADER）确定伊沙佐米在日本患者中相关 AE 的频率和风险。此外，还明确了独特 AE 的发病时间和事后结果。
为了研究伊沙佐米与 AE 的关系，我们分析了 JADER 数据库，该数据库包含 2004 年 4 月至 2021 年 6 月期间向药品和医疗器械管理局自愿报告的 AE。纳入分析的 AE 报告至少有 10 例，AE 信号的存在标准定义为符合比例报告比≥2 和 χ2≥4 的要求。考虑到发病时间和发病结果，对特征性 AE 进行了分析。
在 34 种提取的 AE 中，有 18 种呈现 AE 信号。12 种事后结果的死亡率≥10%，包括感染性休克（50.0%）、感染（41.2%）、心力衰竭（16.7%）、肺炎（14.2%）和肿瘤坏死综合征（13.3%）。发病时间中位数表明，18 种 AE 中有 11 种发生在伊沙佐米开始治疗后约 1 个月内。
我们的研究结果表明，伊沙佐米可能会增加 18 种 AE 的发生率，其中 11 种发生在治疗的第一个月内。此外，有 8 种 AE 的潜在致命结局发生率≥10%。因此，在治疗的第一个月内监测 AE 似乎是必要的。
