基于FAERS数据库的奥拉帕利安全信号挖掘与分析  

A Real-World Study Leveraging US Food and Drug Administration Adverse Events Reporting System of Olaparib

作　　者：李轶凡[1] 王安妮 冯欣[1] LI Yi-fan;WANG An-ni;FENG Xin(Beijing Obstetrics and Gynecology Hospital,Capital Medical University/Beijing Maternal and Child Health Care Hospital,Beijing 100026,China)

机构地区：[1]首都医科大学附属北京妇产医院/北京妇幼保健院,北京100026

出　　处：《中国药学杂志》2021年第20期1631-1636,共6页Chinese Pharmaceutical Journal

基　　金：北京市医院管理中心临床医学发展专项经费资助(ZYLX202119)。

摘　　要：目的利用美国食品药品监督管理局不良事件呈报系统(FDA adverse event reporting system,FAERS)数据库挖掘奥拉帕利上市后安全警戒信号,预警其潜在的不良反应,为奥拉帕利的临床应用和后续研究提供客观资料。方法采用比例失衡分析法中的报告比值比法(ROR)和比例报告比值比法(PRR)同时检测信号。阳性信号标准为:不良反应事件报告数量≥3,ROR法95%置信区间下限>1,PRR法PRR值≥2且χ^(2)≥4。采用相对报告率(RRR)比较不同多腺苷二磷酸核糖聚合酶抑制剂(PARPi)间不良反应事件发生的概率。检索FAERS数据库中2014年1季度至2020年4季度数据进行数据挖掘分析。结果提取到6283例以奥拉帕利为首要怀疑药物的不良反应事件报告,共检测出86个信号,涉及14个系统器官分类,其中有59个信号未在奥拉帕利药品说明书中提及。不良反应事件信号主要涉及胃肠系统疾病(834例),血液及淋巴系统疾病(689例)。以ROR值排序前5位的警戒信号包括红髓组织增生(ROR=128.94,95%CI:40.15~414.14);叶酸缺乏症(ROR=43.01,95%CI:19.15~96.6);恶性肿瘤进展(ROR=41.58,95%CI:37.91~45.6);骨髓异常增生综合征(ROR=31.91,95%CI:25.7~39.62);恶性腹水(ROR=25.68,95%CI:8.22~80.22)。比较奥拉帕利和其他PARPi血液及淋巴系统不良事件信号的RRR值,其中贫血RRR值排序为:尼拉帕利(268.61)>他拉唑帕利(17.79)>奥拉帕利(11.75)>卢卡帕利(6.72),中性粒细胞减少症RRR值排序为:他拉唑帕利(13.30)>尼拉帕利(9.91)>卢卡帕利(3.29)>奥拉帕利(2.28)。结论临床应用奥拉帕利时应充分关注胃肠系统和血液系统不良反应事件信号,用药前需对患者进行用药教育,用药时需对患者的血液指标、肾脏功能进行监测,必要时调整药物剂量,进而有效降低临床用药风险。OBJECTIVE To explor the post-marketing adverse drug event signals of olaparib in the FDA adverse event reporting system(FAERS)database,investigate its potential adverse reactions,and provide references for clinical safe medication.METHODS The signal is detected at the same time using the report ratio method(ROR)and the ratio report ratio method(PRR)in the ratio imbalance analysis method.Positive signal standard:ADE≥3,ROR method lower limit of 95%CI>1,PRR method PRR≥2 andχ^(2)≥4.Relative reporting rate(RRR)was used to compare the probability of adverse events among different PARP inhibitors.The data was extracted from the first quarter of 2014 to the fourth quarter of 2020 in the FAERS database for data mining analysis.RESULTS A total of 6283 adverse event reports with olaparib as the primary suspected drug were extracted.A total of 86 signals were detected,involving 14 system organ classifications,of which 59 signals were not mentioned in the olaparib package insert.Adverse event signals mainly involved gastrointestinal system diseases(834 cases),blood and lymphatic system diseases(689 cases).The top 5 warning signs ranked by ROR value include red pulp tissue hyperplasia(ROR=128.94,95%CI:40.15-414.14);folate deficiency(ROR=43.01,95%CI:19.15-96.6);malignant tumor progression(ROR=41.58,95%CI:37.91-45.6);myelodysplastic syndrome(ROR=31.91,95%CI:25.7-39.62);malignant ascites(ROR=25.68,95%CI:8.22-80.22).Comparing olaparib and other PARPi in the blood and lymphatic system adverse event signals of the RRR value,rank of anemia's RRR:niraparib(268.61)>talazoparib(17.79)>olaparib(11.75)>rucaparib(6.72),Ranking of neutropenia'RRR:talazoparib(13.30)>niraparib(9.91)>rucaparib(3.29)>olaparib(2.28).CONCLUSION FAERS database is used to excavate Olaparib post-marketing safety warning signals.When Olaparib is used clinically,the patient's hematopoietic function should be fully considered,and medication education should be given to the patient before medication.The patient's blood indicators and renal function should be eval

关 键 词：奥拉帕利 不良反应事件报告 美国食品药品监督管理局不良事件呈报系统 数据挖掘 

分 类 号：R95[医药卫生—药学]