FOLFOX方案和FOLFIRI方案致肝毒性的安全信号挖掘

Safety signal mining of FOLFOX scheme and FOLFIRI scheme-induced hepatotoxicity

目的挖掘FOLFOX方案和FOLFIRI方案致肝毒性的安全信号,为临床合理治疗方案的选择、药品不良反应(ADR)的防治提供参考。方法利用报告比值比法和比例报告比值法对美国FDA药品不良事件报告系统中2004年1月1日至2022年6月30日FOLFOX方案和FOLFIRI方案相关药品不良事件(ADE)报告进行分析,挖掘其致肝毒性的潜在安全信号。结果分别检索到FOLFOX方案和FOLFIRI方案相关ADE报告3454、1359份,涉及男、女性患者比例分别为1.50∶1、1.67∶1;上报数排名前5位的国家均为美国、日本、法国、意大利、英国,其报告总和分别占各自报告总数的58.48%和53.79%。有超过90%的患者合并用药不超过5种,FOLFOX方案和FOLFIRI方案联合抗血管生成药物或表皮生长因子受体抑制剂的患者比例分别为45.45%和86.82%。FOLFOX方案致肝毒性相关ADE报告有443份,ADR信号共22个,包括肝窦阻塞综合征、结节状再生增生、药物诱导的肝损伤、血胆红素升高等;FOLFIRI方案肝毒性相关ADE报告有128份,ADR信号共9个,包括血胆红素升高、肝毒性、脂肪性肝炎、肝脂肪变性等。结论FOLFOX方案和FOLFIRI方案所致肝毒性类型不同,临床应加强用药监护,保障患者用药安全。

OBJECTIVE To mine the safety signals of FOLFOX scheme and FOLFIRI scheme-induced hepatotoxicity,and to provide reference for the selection of clinical rational treatment plan and the prevention and treatment of drug adverse reaction(ADR).METHODS Reporting odds ratio method and proportion report ratio method were used to analyze adverse drug event(ADE)reports of FOLFOX scheme and FOLFIRI scheme in FDA adverse event reporting system during January 1,2004-June 30,2022.The potential safety signals of FOLFOX scheme and FOLFIRI scheme-induced hepatotoxicity were mined.RESULTS The amounts of ADE reports related to FOLFOX scheme and FOLFIRI scheme were respectively 3454 and 1359;the proportions of male and female patients involved were 1.50∶1 and 1.67∶1 in these two schemes,respectively.The top five countries with the largest number of reports were the United States,Japan,France,Italy and the United Kingdom,respectively accounting for 58.48%and 53.79%of the total reported cases.More than 90%of patients took no more than 5 drugs in combination,the proportion of patients receiving FOLFOX scheme and FOLFIRI scheme combined with anti-angiogenic drugs or epidermal growth factor receptor inhibitors was 45.45%and 86.82%,respectively.Totally 443 ADE reports of FOLFOX scheme-induced hepatotoxicity were collected,and 22 ADR signals were generated,including hepatic sinusoidal obstruction syndrome,nodular regenerative hyperplasia,drug-induced liver injury,blood bilirubin increased,etc.Totally 128 ADE reports of FOLFIRI schemeinduced hepatotoxicity were reported,and 9 ADR signals were generated,including blood bilirubin increased,hepatotoxicity,steatohepatitis,hepatic steatosis,etc.CONCLUSIONS FOLFOX scheme and FOLFIRI scheme can cause different types of hepatotoxicity.Clinical drug monitoring should be strengthened to guarantee drug safety.