Department of Pharmacology, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia.
Department of Biochemistry, College of Sciences, University of Jeddah, Jeddah, Saudi Arabia.
Int J Clin Pharm. 2024 Apr;46(2):368-381. doi: 10.1007/s11096-023-01671-0. Epub 2023 Dec 26.
Imatinib, a potent inhibitor of targeted protein tyrosine kinases, treats chronic myeloid leukaemia (CML). Data on imatinib-associated changes in hepatic and thyroid functions are limited and conflicting.
To report the prevalence of hepatic and thyroid toxicity associated with the use of imatinib in CML patients.
Articles for the systematic review were selected from electronic databases (PubMed, CINALH, Web of Science). Readily accessible peer-reviewed full articles in English published 1st January 2000 to 18th July 2023 were included. The search terms included combinations of: imatinib, CML, liver toxicity, hepatic toxicity, thyroid toxicity. Screening of titles, abstracts, full text articles was conducted independently by two reviewers. Inclusions and exclusions were recorded following PRISMA guidelines. Detailed reasons for exclusion were recorded. Included articles were critically appraised.
Ten thousand one hundred and twenty-three CML patients were reported in the 82 included studies corresponding to 21 case reports, 2 case series, 39 clinical trials and 20 observational studies were selected. Excluding case studies/reports, 1268 (12.6%; n = 1268/10046) hepatotoxicity adverse events were reported, of which 64.7% were rated as mild grade I & II adverse events, 363 (28.6%) as severe, grade III and IV adverse events; some led to treatment discontinuation, liver transplantation and fatal consequences. Twenty (35.1%) studies reported discontinuation of imatinib treatment due to the severity of hepatic toxicity. Fourteen (8.4%, n = 14/167) thyroid dysfunction adverse events were reported.
High frequency of mild and severe hepatotoxicity, associated with imatinib in CML patients, was reported in the published literature. Low numbers of mild and manageable thyroid toxicity events were reported.
伊马替尼是一种有效的靶向蛋白酪氨酸激酶抑制剂，用于治疗慢性髓性白血病（CML）。有关伊马替尼相关肝、甲状腺功能变化的数据有限且存在争议。
报告 CML 患者使用伊马替尼相关肝毒性和甲状腺毒性的发生率。
系统评价的文献选自电子数据库（PubMed、CINALH、Web of Science）。纳入 2000 年 1 月 1 日至 2023 年 7 月 18 日发表的易于获取的同行评议全文英语文章。检索词包括：伊马替尼、CML、肝毒性、肝毒性、甲状腺毒性。两名评审员独立筛选标题、摘要和全文文章。按照 PRISMA 指南记录纳入和排除标准。记录排除的详细原因。对纳入的文章进行批判性评价。
82 项研究共报告了 1123 例 CML 患者，涉及 21 例病例报告、2 例病例系列研究、39 项临床试验和 20 项观察性研究。排除病例研究/报告后，共报告了 1268 例（12.6%；n=1268/10046）肝毒性不良事件，其中 64.7%为轻度 I&II 级不良事件，363 例（28.6%）为严重、III&IV 级不良事件；一些导致治疗中断、肝移植和致命后果。20 项（35.1%）研究报告因肝毒性严重而停止伊马替尼治疗。14 项（8.4%，n=14/167）研究报告了甲状腺功能障碍不良事件。
在已发表的文献中，报告了 CML 患者使用伊马替尼时出现的高频率的轻度和重度肝毒性，以及与伊马替尼相关的肝毒性。报告的轻度和可管理的甲状腺毒性事件数量较少。
