目的 利用美国食品药品管理局不良事件报告系统(FAERS)数据库对替诺福韦二吡呋酯(TD)和丙酚替诺福韦(TA)的不良事件(AE)及肾脏安全性进行数据挖掘,以期为临床安全用药提供参考.方法 分别采用报告比值比法、比例报告比值法、综合标准法和贝叶斯置信度递进神经网络法,对FAERS数据库中 2004 年第 1 季度至2023年第1季度的TD和TA相关AE报告进行数据挖掘,分析风险信号分布及强度,并采用标准国际医学用语词典(MedDRA)分析查询(SMQ)检索其中的"急性肾脏衰竭"和"慢性肾脏疾病"报告并开展深入分析.结果 分别提取到TD和TA为首要怀疑药物的AE报告 19 530 份和 1 587 份,男性均多于女性,年龄集中分布于 45~65 岁,同时满足4种挖掘方法的信号数分别为185和68个.两药的高频AE分布存在明显差异,TD显示以骨骼和肾脏疾病为主要风险信号,表现为骨密度降低、骨骼损伤、骨质疏松症、慢性肾脏疾病、肾衰竭等;TA以全身性疾病为主,骨骼和肾脏损伤相关报告很少,且多数为阴性信号.进一步肾脏安全性AE相关信号显示相似的结果.结论 TD和TA在高频AE、系统器官分布和总体安全性等方面存在一定差异,特别是肾脏和骨骼安全性.既往存在肾脏和骨骼疾病的患者可优选TA,但应考虑TA上市时间短,目前报告数量少可能带来的偏差.临床应持续关注两药的安全性.
Objective To explore the adverse events and renal safety of tenofovir disoproxil(TD)and tenofovir alafenamide(TA)by data mining from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,so as to provide reference for clinical drug safety.Methods The adverse events of TD and TA reported in FAERS database between the first quarter of 2004 and the first quarter of 2023 were analyzed with the methods of the reporting odds ratio(ROR)method,proportional reporting ratio(PRR)method,the Medicines and Healthcare products Regulatory Agency(MHRA)method,and Bayesian Confidence Propagation Neural Network(BCPNN)method.The distribution and intensity of risk signals of the data were analyzed,and the SMQ search tool was employed to conduct in-depth analysis of"acute renal failure"and"chronic kidney disease".Results A total of 19 530 and 1 587 reports were extracted as primary suspect drugs for TD and TA.There were more males than females were found in reports,and the age was concentrated in 45-65 years old,and the number of signals satisfying the four excavation methods was 185 and 68,respectively.The high-frequency adverse event distribution showed significant differences between TD and TA.The main risk signals of TD were bone and renal diseases,manifested as decreased bone density,bone injury,osteoporosis,chronic kidney disease,and renal failure.The main risk signals of TA was systemic disease with few reports of bone and renal damage,most of which were negative signals.Further analysis of renal safety showed similar results.Conclusion There are certain differences in terms of high-frequency adverse events,systemic organ distribution,and overall safety between TD and TA,especially the safety of renal and bone.Patients with pre-existing renal and bone diseases prefer TA to TD,however,the short time to market and the deviation caused by the small number of reports for TA,the safety of the two drugs should be continuously paid attention to.