摘要
目的:检测表皮生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)类代表药物"吉非替尼"和"厄洛替尼"上市后的安全信号,为临床合理用药提供参考。方法:调取美国FDA不良事件报告系统(FDA Adverse Event Reporting System,FAERS)数据库2004年1月1日至2017年10月25日收录的以吉非替尼、厄洛替尼为首要怀疑对象的不良事件(adverse drug events,ADEs)报告,采用报告比值比(ROR)信号检测方法对前述药品进行ADEs信号检测,重点评估和比较胃肠道、皮肤和皮下组织、肾脏泌尿、肝脏、血液、代谢及营养、眼部等器官系统分类(SOC)所涉及的安全信号。结果:提取FAERS数据库得到吉非替尼ADEs报告4 839例,其中女性报告2 019(41. 72%)例,男性报告2 020(41. 74%)例;厄洛替尼ADEs报告26 150例,女性报告13 269(50. 74%)例,男性报告12 008(45. 92%)例。吉非替尼以医生(2 184,45. 14%)上报为主;厄洛替尼(12 556,48. 02%)以消费者上报为主。经ROR法检测:胃肠道系统相关ADEs中,吉非替尼在胃溃疡(ROR=2. 67,95%CI:1. 77～4. 02)、肠梗阻(ROR=4. 26,95%CI:2. 80～6. 48)、黑便(ROR=2. 67,95%CI:1. 77～4. 02)显示阳性信号,而厄洛替尼未出现类似信号,但厄洛替尼在肠穿孔(ROR=1. 78,95%CI:1. 30～2. 42)显示阳性信号;皮肤和皮下组织相关ADEs,2种药品信号强度均较高,且痤疮性皮炎在吉非替尼(ROR=25. 95,95%CI:25. 95～45. 32)、厄洛替尼(ROR=43. 65,95%CI:38. 75～49. 18)中信号突出;肾脏泌尿系统以及肝胆系统相关ADEs,吉非替尼的信号最强,厄洛替尼信号强度较弱;眼部系统ADEs信号主要集中在厄洛替尼,其中以结膜炎ROR=4. 34,95%CI:3. 51～5. 38)的信号最强。另外,吉非替尼所致的性功能下降(ROR=12. 94,95%CI:8. 32～20. 11)、间质性肺炎(ROR=32. 22,95%CI:28. 77～36. 08)等安全信号高于厄洛替尼。结论:基于真实世界的ADEs信号检测有助于药物上市后的安全性评价,降低
Objective:To detect and evaluate the safety signals of gefitinib and erlotinib in post-marketing experience,and provide reference for clinical practice.Methods:Reporting odd ratio (ROR)data mining algorithm was used to investigate the signals of adverse drug events (ADEs)for gefitinib and erlotinib from FAERS from January 1,2004to October 31,2017.The high-risk signals involved in system organ class (SOC)of gastrointestinal disorders,skin and subcutaneous tissue disorders,renal and urinary disorders,hepatobiliary disorders,blood and lymphatic system disorders,metabolism and nutrition disorders,and eye disorders were analyzed and evaluated. Results:A total of 4839reports were screened out for gefitinib,including 2019reports on females and 2020 reports on males,respectively.A total of 26150reports were screened out for erlotinib,including 13269reports on females and 12008reports on males,respectively.The ADE reports for gefitinib were submitted mainly by doctors and those for erlotinib were by patients.As shown by ROR detection,the high-risk ADE signals of gastrointestinal disorders of gefitinib mainly concentrated in gastric ulcer,ileus,melaena,etc,while erlotinib showed positive signal in intestinal perforation.Both drugs showed strong signals in skin and subcutaneous tissue ADEs,especially for dermatitis acneiform.There was no significant signal for erlotinib.Gefitinib had the most strong signal intensity for renal and urinary,hepatobiliary,blood and lymphatic system-related ADEs.The signal of eyes-related ADEs mainly concentrated in erlotinib.Conclusion:The study of ADE signals based on the real world clinical setting is helpful to evaluate the safety of post marketing drugs and reduce the risk of clinical use of drugs.
作者
田晓江
唐学文
季欢欢
贾运涛
TIAN Xiao-jiang;TANG Xue-wen;JI Huan-huan;JIA Yun-tao(School of Pharmacy,Chongqing Medical University,Chongqing 400016,China;Depariment of Pharmacy,Children's Hospital of Chongqing Medical University,Ministry of Education Key Laboratory of Child Development and Disorders,China International Science and Technology Cooperation Base of Child Development and Critical Disorders,Chongqing Key Laboratory of Pediatrics,Chongqing 400014,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2018年第22期2705-2711,共7页
Chinese Journal of New Drugs
基金
重庆市科委民生项目(cstc2016shm8zxl30048)
重庆市卫计委医学科研项目(2016ZDXM017)
