基于美国FDA不良事件报告系统数据库的瑞戈非尼肝胆系统损伤风险分析  

Risk analysis of regorafenib related hepatobiliary system injury based on the US Food and Drug Administration Adverse Event Reporting System

作　　者：龙霞[1] 曾晓欢 干小红[1] Long Xia;Zeng Xiaohuan;Gan Xiaohong(Department of Pharmacy,Chengdu Fifth People′s Hospital,Chengdu 611130,China;Department of Pharmacy,Southwest Medical University,Sichuan Province,Luzhou 646000,China)

机构地区：[1]成都市第五人民医院药剂科,611130 [2]西南医科大学药学院,四川省泸州市646000

出　　处：《药物不良反应杂志》2020年第4期227-232,共6页Adverse Drug Reactions Journal

摘　　要：目的探讨瑞戈非尼相关肝胆系统损伤的风险及影响因素。方法检索美国食品药品管理局不良事件报告系统(FAERS)2012年第4季度至2018年第3季度收到的瑞戈非尼相关肝胆系统不良事件报告数据。采用报告比值比法(ROR)与比例报告比值比法(PRR)对有关瑞戈非尼的肝胆系统不良事件信号进行筛选和统计分析,用logistic回归分析其影响因素。结果共检索到瑞戈非尼相关不良事件报告26013份,筛选出28个首选术语为可疑肝胆系统相关的不良事件信号。采用ROR和PRR及其95%置信区间(CI)下限对不良事件信号强度进行分类排序的结果显示,黄疸及胆红素升高信号最强(ROR=8.56,95%CI下限:7.66;PRR=8.46,95%CI下限:7.58);其次为其他实验室检查异常(ROR=6.05,95%CI下限:4.95;PRR=6.03,95%CI下限:4.94)和肝脏相关疾病(ROR=5.46,95%CI下限:4.71;PRR=5.43,95%CI下限:4.69)。logistic回归分析结果显示,相对瑞戈非尼剂量≤80 mg/d,剂量为>80~<160 mg/d时,肝胆系统不良事件发生的风险更高(OR=1.702,95%CI:1.230~2.356,P=0.001);相对其他肿瘤,胃肠道间质瘤患者发生肝胆系统不良事件的风险更低(OR=0.436,95%CI:0.240~0.792,P=0.006)。结论瑞戈非尼有导致肝胆系统损伤的风险,较高的药物剂量可能与肝胆系统损伤风险增加有关。Objective To explore the risks and influencing factors of regorafenib related hepatobiliary system injury.Methods Reports of regorafenib related hepatobiliary system adverse events received from 4th quarter,2012 to 3rd quarter,2018 in the US Food and Drug Administration Adverse Event Reporting System(FAERS)database were collected.The signal intensity of hepatobiliary system adverse events related to regorafenib was screened and statistically analyzed by report odds ratio(ROR)and proportional report ratio(PRR),and their influencing factors were analyzed by logistic regression analysis.Results A total of 26013 adverse event reports related to regorafenib were retrieved,and 28 preferred terms were screened as suspicious hepatobiliary system related adverse event signals.Results from sorting the signal intensity of adverse events using ROR,PRR and their lower limit of 95%confidence interval(CI)showed that elevation of jaundice and bilirubin had the strongest signal(ROR=8.56,95%CI lower limit:7.66;PRR=8.46,95%CI lower limit:7.58),followed by other laboratory abnormalities(ROR=6.05,95%CI lower limit:4.95;PRR=6.03,95%CI lower limit:4.94)and then liver related diseases(ROR=5.46,95%CI lower limit:4.71;PRR=5.43,95%CI lower limit:4.69).Logistic regression analysis showed that the risk of hepatobiliary system adverse events was higher when the regorafenib dose was>80~<160 mg/d,compared with the dose of≤80 mg/d(OR=1.702,95%CI:1.230-2.356,P=0.001),and was lower in patients with gastrointestinal stromal tumors,compared with other tumors(OR=0.436,95%CI:0.240-0.792,P=0.006).Conclusion Regorafenib has the risk of hepatobiliary system injury,and a higher dose may be related to the increased risk.

关 键 词：血管生成抑制剂 抗肿瘤药 药物不良反应报告系统 化学和药物性肝损伤 瑞戈非尼 

分 类 号：R9[医药卫生—药学]