Relationship between Anaplastic Lymphoma Kinase Inhibitors and Epileptic Seizure Disorder: A Post-Marketing Surveillance Study.

IF 2.5 3区医学 Q3 ONCOLOGY Oncology Pub Date : 2024-01-01 Epub Date: 2024-05-20 DOI:10.1159/000539426

Yoshihiro Noguchi, Hiroki Asano, Rikuto Masuda, Yuta Teshigawara, Makiko Go, Michio Kimura, Eiseki Usami, Tomoaki Yoshimura

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Abstract

Introduction: Anaplastic lymphoma kinase (ALK) has been to be involved in the uptake and regulation of dopamine 2 receptor (D2R), a G protein-coupled receptor expressed in various brain regions. Therefore, it is crucial to understand the relationship between ALK inhibitors and seizures is an important issue. This study investigated the relationship between ALK inhibitors and seizures.

Methods: This study investigated the relationship between ALK inhibitors and seizures through a disproportionality analysis using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The target drugs were the ALK inhibitors crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib. The seizures covered were defined high-level group term (HLGT): "Seizures (incl. subtype)" including high-level term (HLT): "seizures and seizure disorders NEC." This study used the information component (IC), a signal score, as a Bayesian statistical method for disproportionality analysis. The signal detection criteria used in this study were the same as those reported previously: a lower limit of 95% credible interval (CrI) for IC >0.

Results: The signal scores of '"seizures and seizure disorders not elsewhere classified (NEC)" "for each ALK inhibitor were crizotinib (IC: -0.00052, 95% CrI: -0.38-0.27), ceritinib (IC: 1.18, 95% CrI: 0.68-1.54), alectinib (IC: 0.68, 95% CrI: 0.19-1.02), brigatinib (IC: 1.04, 95% CrI: 0.32-1.54), and lorlatinib (IC: 0.82, 95% CrI: 0.11-1.32). On the other hand, "generalized tonic-clonic seizures," "partial simple seizures NEC," "absence seizures," and "partial complex seizures" had no or few reported cases, and no signal was detected.

Conclusion: To our knowledge, this is the first report to evaluate the relationship between ALK inhibitors and seizures using post-marketing surveillance data. These results suggest that ceritinib, alectinib, brigatinib, and lorlatinib, which are highly brain-migrating drugs, are associated with seizures.

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无性淋巴瘤激酶 (ALK) 抑制剂与癫痫发作障碍之间的关系：上市后监测研究》。

导言：ALK参与了D2R的吸收和调节，D2R是一种表达于不同脑区的G蛋白偶联受体。因此，了解 ALK 抑制剂与癫痫发作之间的关系至关重要。本研究调查了ALK抑制剂与癫痫发作之间的关系：本研究通过使用 FAERS 进行比例失调分析，调查 ALK 抑制剂与癫痫发作之间的关系。目标药物为ALK抑制剂crizotinib、ceritinib、alectinib、brigatinib和lorlatinib。所涵盖的癫痫发作定义为 HLGT："癫痫发作（包括亚型）"，包括 HLT："癫痫发作和癫痫发作障碍 NEC"。本研究使用信号得分 IC 作为贝叶斯统计方法进行不相称性分析：每种 ALK 抑制剂的''癫痫发作和癫痫发作障碍 NEC''信号得分分别为克唑替尼（IC：-0.00052，95%CrI：-0.38-0.27）、色瑞替尼（IC：1.18，95%CrI：0.68-1.54）、阿埃替尼（IC：0.68，95%CrI：0.19-1.02）、布瑞替尼（IC：1.04，95%CrI：0.32-1.54）和洛拉替尼（IC：0.82，95%CrI：0.11-1.32）。另一方面，"全身强直-阵挛性发作"、"部分单纯性发作 NEC"、"失神发作 "和 "部分复杂性发作 "没有或仅有少数病例报道，也未检测到信号：据我们所知，这是第一份利用上市后监测数据评估 ALK 抑制剂与癫痫发作之间关系的报告。这些结果表明，ceritinib、alectinib、brigatinib和lorlatinib这些高度脑迁移的药物与癫痫发作有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oncology 医学-肿瘤学

CiteScore

6.00

自引率

2.90%

发文量

审稿时长

6-12 weeks

期刊介绍： Although laboratory and clinical cancer research need to be closely linked, observations at the basic level often remain removed from medical applications. This journal works to accelerate the translation of experimental results into the clinic, and back again into the laboratory for further investigation. The fundamental purpose of this effort is to advance clinically-relevant knowledge of cancer, and improve the outcome of prevention, diagnosis and treatment of malignant disease. The journal publishes significant clinical studies from cancer programs around the world, along with important translational laboratory findings, mini-reviews (invited and submitted) and in-depth discussions of evolving and controversial topics in the oncology arena. A unique feature of the journal is a new section which focuses on rapid peer-review and subsequent publication of short reports of phase 1 and phase 2 clinical cancer trials, with a goal of insuring that high-quality clinical cancer research quickly enters the public domain, regardless of the trial’s ultimate conclusions regarding efficacy or toxicity.