| アブストラクト | BACKGROUND: Patients with anaplastic lymphoma kinase (ALK)-positive malignancies increasingly rely on ALK inhibitors (ALKis) as first-line therapy, yet thromboembolism (TE) across the ALKi family and its impact on patients' safety remain incompletely characterized, particularly in the real-world populations. OBJECTIVE: The aim of this study was to evaluate the real-world TE risks associated with ALKis using pharmacovigilance data mining and to identify and characterize the high-risk contributors to TE. METHODS: We extracted 52,808 adverse event (AE) reports from the FDA Adverse Event Reporting System (2013-2024), including 17,124 ALKi-treated patients. TE signal strength was calculated via disproportionality analysis and presented by the lower limit of reporting odds ratio (ROR(025)) and information component (IC(025)). Multivariate logistic regression and time-to-onset (TTO) analyses were conducted to characterize the risk factors. RESULTS: Among ALKi users, 251 TE cases were identified. Crizotinib exhibited significant TE safety signals for embolism (ROR(025) = 2.66; IC0(25) = 1.19), pulmonary artery thrombosis (ROR(025) = 4.94; IC0(25) = 1.01), pulmonary thrombosis (ROR(025) = 1.29; IC0(25) = 0.13), and venous thrombosis limb (ROR(025) = 1.66; IC0(25) = 0.08). Older age (OR = 1.006, P = 2.40e-06), male sex (OR = 1.47, P = 2.00e-16), and crizotinib use (OR = 2.79, P = 1.59e-05) independently predicted fatal TE outcomes. Female patients <65 years experienced earlier TE onset (median 14 vs. 44-53 days; P = 0.006). CONCLUSION: This study validates the elevated TE safety signal strength of crizotinib in the real-world settings, while no disproportionate TE signals were detected for other ALKi in the FAERS database. Clinicians could prioritize agent-specific risks, especially in older male patients and during early treatment phases. |
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| ジャーナル名 | Frontiers in pharmacology |
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| Pubmed追加日 | 2026/9/22 |
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| 投稿者 | Hu, Rong; Ai, Qing; Zhang, Hui; Liu, Min; Qiu, Yuan; He, Yingyi |
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| 組織名 | Department of Pharmacy, Fujian Children's Hospital (Fujian Branch of Shanghai;Children's Medical Center), College of Clinical Medicine for Obstetrics &;Gynecology and Pediatrics, Fuzhou, China.;Department of Hematology/Oncology, Fujian Children's Hospital (Fujian Branch of;Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics;& Gynecology and Pediatrics, Fuzhou, China.;Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of;Guangzhou Medical University, State Key Laboratory of Respiratory Disease,;National Clinical Research Center for Respiratory Disease, Guangzhou Institute of;Respiratory Health, Guangzhou, China.;Department of Pediatrics, The Chinese University of Hong Kong, Hong Kong SAR,;China.;State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty;of Medicine and Life Sciences, Xiamen University, Xiamen, China. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/42769446/ |
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