| アブストラクト | INTRODUCTION: Recently, cases of cardiovascular toxicities, such as pericarditis, caused by anaplastic lymphoma kinase (ALK) inhibitors have been reported; however, whether these adverse events are common among all ALK inhibitors remains unclear. AIMS: This study aimed to clarify the cardiovascular toxicity profile of ALK inhibitors using an adverse event spontaneous report database. METHODS: We analyzed data from VigiBase, the WHO global database of individual safety reports, from its inception in 1968 to December 2021. We calculated the reporting odds ratio to evaluate the association between ALK inhibitors (crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib) and 21 cardiovascular adverse events. Time to onset of pericarditis from ALK inhibitor administration was analyzed. RESULTS: Of the 27,994,584 reports, 19,911 involved treatment with ALK inhibitors. Among the 21 cardiovascular toxicities, only pericarditis signals were detected with all five ALK inhibitors (crizotinib [reporting odds ratios (ROR), 4.7; 95% CI 3.63-6.15], ceritinib [ROR, 12.9; 95% CI 9.37-17.79], alectinib [ROR, 4.8; 95% CI 3.15-7.42], brigatinib [ROR, 3.5; 95% CI 1.33-9.46], and lorlatinib [ROR, 6.4; 95% CI 3.60-11.22]). For torsade de pointes/QT prolongation, signals were detected with crizotinib (ROR, 5.0; 95% CI 3.72-6.77) and ceritinib (ROR, 4.2; 95% CI 2.17-8.05), whereas for hypertension, they were identified only with brigatinib (ROR, 3.9; 95% CI 2.88-5.20), and for heart failure, they were detected with alectinib (ROR, 2.2; 95% CI 1.60-2.90), crizotinib (ROR, 2.1; 95% CI 1.72-2.48), and lorlatinib (ROR, 2.0; 95% CI 1.27-3.23). Regarding time-to-onset analysis from drug administration to adverse event reporting, for pericarditis, it ranged from 52.5 days for alectinib to 166.5 days for crizotinib. CONCLUSIONS: Systematic evaluation of ALK inhibitor-associated adverse events revealed differences in the cardiotoxicity profiles among ALK inhibitors. Understanding the differences in the cardiovascular toxicity profile of each ALK inhibitor will contribute to safe drug therapy when switching between ALK inhibitors. |
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| ジャーナル名 | Drug safety |
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| 投稿日 | 2023/4/28 |
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| 投稿者 | Niimura, Takahiro; Miyata, Koji; Hamano, Hirofumi; Nounin, Yuuki; Unten, Hiroto; Yoshino, Masaki; Mitsuboshi, Satoru; Aizawa, Fuka; Yagi, Kenta; Koyama, Toshihiro; Goda, Mitsuhiro; Kanda, Yasunari; Izawa-Ishizawa, Yuki; Zamami, Yoshito; Ishizawa, Keisuke |
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| 組織名 | Department of Clinical Pharmacology and Therapeutics, Tokushima University;Graduate School of Biomedical Sciences, 3-18-15 Kuramoto, Tokushima, 770-8503,;Japan. niimura@tokushima-u.ac.jp.;Clinical Research Center for Developmental Therapeutics, Tokushima University;Hospital, Tokushima, Japan. niimura@tokushima-u.ac.jp.;Japan.;Hospital, Tokushima, Japan.;Department of Pharmacy, Okayama University Hospital, Okayama, Japan.;Department of Pharmacy, Tokushima University Hospital, Tokushima, Japan.;Department of Pharmacy, Niigata Prefectural Cancer Center Hospital, Niigata,;Department of Pharmacy, Kaetsu Hospital, Niigata, Japan.;Department of Health Data Science, Graduate School of Medicine, Dentistry, and;Pharmaceutical Sciences, Okayama University, Okayama, Japan.;Division of Pharmacology, National Institute of Health Sciences, Kawasaki, Japan.;Department of General Medicine, Taoka Hospital, Tokushima, Japan. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/37106270/ |
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