基于真实世界监测数据挖掘与分析奥希替尼上市后的不良反应信号

目的：挖掘、分析奥希替尼上市后的不良反应信号，为提高临床用药安全提供依据。方法：采用报告比值比法、比例报告法挖掘FAERS数据库，提取2015年第1季度至2021年第1季度的不良反应信息，使用SQL SERVER（2008 R2）数据库整理，利用SPSS 26.0对患者年龄、体质量、用药剂量、用药疗程等信息做统计分析。结果：共收集9 163 471份报告，筛选后得到20 398份与奥希替尼相关的ADR报告，挖掘出122个ADR信号，涉及15个组织系统。122个信号中存在胸膜炎、肌酸激酶升高、甲状腺功能亢进等说明书中未记载的不良反应。完整报告以呼吸系统ADR和心脏器官ADR占比最大。患者的性别、体质量、用药疗程、国籍对呼吸系统ADR的影响，与其他系统相比，差异具有统计学意义（P＜0.05）。而患者的性别、年龄、用药疗程对心脏器官ADR的影响更大（P＜0.05）。结论：对于既往存在慢性呼吸系统疾病、体型偏瘦的亚裔男性患者，尤其联合使用PD-1/PD-L1治疗时，在开始使用奥希替尼的90 d内，应加强药学监护；治疗早期（≤30 d）更应关注药物的心脏毒性，特别是存在心血管病史的老年女性患者。

Mining and analyzing adverse reaction signals of osimertinib after listing based on real-world monitoring data

OBJECTIVE Excavate and analyze the adverse reaction signals of Osimertinib after listing,so as to provide basis for improving the safety in clinical medication.METHODS ROR method and PRR method were used to mine FAERS database to extract adverse reactions information from the first quarter of 2015 to the first quarter of 2021.The information was sorted out by using SQL SERVER (2008 R2) database,and SPSS 26.0 was used for statistical analysis of patients’ age,weight,medication dose,medication course,etc.RESULTS A total of 9 163 471 reports were collected in 25 quarters,and 20 398 ADR reports related to osimertinib were obtained after screening.122 ADR signals were mined,involving 15 organizational systems.Among 122 signals,pleurisy,blood creatine phosphokinase increased,alanine aminotransferase increased,and other unrecorded adverse reactions were found.In the complete report,ADRs of respiratory,thoracic,and mediastinal disorder and ADRs of cardiac disorder accounted for the largest proportion.Gender,body weight,medication course and nationality of patients had statistically significant effects on ADRs of respiratory,thoracic,and mediastinal disorder compared with others(P＜0.05).The gender,age and medication course of patients had greater influence on cardiotoxicity(P＜0.05).CONCLUSION For lean Asian male patients with chronic respiratory diseases in the past,especially when combined with PD-1/PD-L1 therapy,pharmaceutical care should be strengthened within 90 days after starting to use osimertinib.More attention should be paid to the cardiotoxicity of drugs in the early stage of treatment(≤30 days),especially in elderly women with cardiovascular history.