Pharmacovigilance evaluation of the relationship between impaired glucose metabolism and BCR-ABL inhibitor use by using an adverse drug event reporting database
Pharmacovigilance evaluation of the relationship between impaired glucose metabolism and BCR-ABL inhibitor use by using an adverse drug event reporting database
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DOI：
10.1002/cam4.1920
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发表时间：
2019-01-01
期刊：
影响因子：
4
通讯作者：
Ishizawa, Keisuke
中科院分区：
文献类型：
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作者：
Okada, Naoto;Niimura, Takahiro;Ishizawa, Keisuke
断点簇区域-Abelson小鼠白血病（BCR-ABL）抑制剂显著改善慢性粒细胞白血病的预后。然而，高治疗依从性是BCR-ABL抑制剂成功治疗所必需的。因此，充分了解BCR-ABL抑制剂的不良事件特征至关重要。尽管在试验中观察到许多不良事件，但由于严格的入选标准或有限的随访时间，仅基于临床试验结果准确识别不良事件是困难的。特别是，BCR-ABL受体诱导的糖代谢受损仍然存在争议。使用自发报告系统进行药物警戒评价有助于分析临床环境中的药物相关不良事件。因此，我们使用FDA不良事件报告系统（FAERS）和日本药物不良事件报告（JADER）数据库对BCR-ABL受体诱导的糖代谢受损进行信号检测分析。仅在使用尼洛替尼时检测到葡萄糖代谢受损报告率增加的信号，而在使用其他BCR-ABL抑制剂时未检测到这些信号。亚组分析显示，在男性和年轻患者中，尼洛替尼相关的糖代谢受损报告率明显增加。尽管基于FAERS和JADER的信号检测分析不能完全确定因果关系，但我们的研究表明，BCR-ABL抑制剂对葡萄糖代谢的影响不同，并为选择合适的BCR-ABL抑制剂提供了有用的信息。
Breakpoint cluster region-Abelson murine leukemia (BCR-ABL) inhibitors markedly improve the prognosis of chronic myeloid leukemia. However, high treatment adherence is necessary for successful treatment with BCR-ABL inhibitors. Therefore, an adequate understanding of the adverse event profiles of BCR-ABL inhibitors is essential. Although many adverse events are observed in trials, an accurate identification of adverse events based only on clinical trial results is difficult because of strict entry criteria or limited follow-up durations. In particular, BCR-ABL inhibitor-induced impaired glucose metabolism remains controversial. Pharmacovigilance evaluations using spontaneous reporting systems are useful for analyzing drug-related adverse events in clinical settings. Therefore, we conducted signal detection analyses for BCR-ABL inhibitor-induced impaired glucose metabolism by using the FDA Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) database. Signals for an increased reporting rate of impaired glucose metabolism were detected only for nilotinib use, whereas these signals were not detected for other BCR-ABL inhibitors. Subgroup analyses showed a clearly increased nilotinib-associated reporting rate of impaired glucose metabolism in male and younger patients. Although FAERS- and JADER-based signal detection analyses cannot determine causality perfectly, our study suggests the effects on glucose metabolism are different between BCR-ABL inhibitors and provides useful information for the selection of appropriate BCR-ABL inhibitors.