Data mining and analysis of adverse drug reaction signals for combined serine/threonine-protein kinase B-raf/mitogen-activated protein kinases inhibitors in the U.S.FDA Adverse Event Reporting System
LIU Hong
WANG Wen-juan
BAI Yu
ZHANG Guan-min
ZHANG Yan-hua
Abstract：Objective:To assess the differences in adverse drug reactions(ADR)across three BRAF/MEK inhibitor combinations,vemurafenib with cobimetinib,dabrafenib with trametinib,and encorafenib with binimetinib thus to improve clinical medication safety.Methods:ADR reports were collected from the U.S.FDA Adverse Event Reporting System from the first quarter of 2011 to the second quarter of 2023.Data analysis was conducted using the reporting odds ratio,Bayesian confidence propagation neural network method,and chi-square tests for inter-group comparisons.Results:The analysis included 17 982 ADR reports.Dabrafenib in combination with trametinib had the highest number of reports(12 746)and the highest proportion of mortality outcomes(26.62%)compared to other combinations.The primary adverse effects involved systemic organs,including skin and subcutaneous tissue disorders,systemic diseases,reactions at the administration site,and gastrointestinal system diseases.Notably,strong associations were found between serous retinopathy and both the vemurafenib with cobimetinib and encorafenib with binimetinib combinations.The fatal probability of organic brain syndrome ADR in the vemurafenib combined with cobimetinib regimen was 100.00%.Conclusion:Clinicians should be particularly cautious of the risk of death from organic brain syndrome ADR in the vemurafenib combined with cobimetinib regimen.Variation exists in the strength of associations between different BRAF/MEK inhibitor combinations and ADR affecting specific systemic organs.Clinicians should select appropriate therapeutic strategies based on individual patient needs and effectively monitor ADR.
Keywords：pharmacovigilanceadverse drug reactionsserine/threonine-protein kinase B-rafmitogen-activated protein kinaseinhibitors
Publication Date：2024-10-31
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：7( 2178-2184 )