基于FAERS数据库的核苷(酸)类似物相关各种肌肉骨骼及结缔组织疾病事件信号挖掘研究

Signal data mining for nucleos(t)ide analogues related musculoskeletal and connective tissue disorder events based on FAERS

目的:基于美国食品和药品管理局不良反应报告系统(FAERS)的数据,挖掘核苷(酸)类似物(NAs)相关各种肌肉骨骼及结缔组织疾病事件信号,为临床合理用药提供参考。方法:下载并清洗2017年第一季度至2022年第三季度FAERS数据,提取NAs相关各种肌肉骨骼及结缔组织疾病事件,采用报告比值比法(ROR)和综合标准法(MHRA)检测信号。结果:共提取到NAs相关的各种肌肉骨骼及结缔组织疾病不良事件(ADEs)22 416条,其中富马酸替诺福韦二吡呋酯(TDF)21 068条、阿德福韦酯(ADV)626条、拉米夫定(LAM)426条、恩替卡韦(ETV)127条以及富马酸丙酚替诺福韦(TAF)169条,检测出的信号数分别为TDF34个、ADV22个、LAM13个、ETV2个和TAF2个。在高位组语层面,TDF、ADV、LAM、TAF的信号主要分布在骨骼类疾病(不包括先天性疾病及骨折),分别为97.33%、67.08%、72.73%和78.57%。ETV的信号主要分布在肌肉类疾病,为86.96%。且TDF、ADV、LAM的信号以骨质疏松、骨软化等代谢性骨病为主,而TAF和ETV的信号则不涉及代谢性骨病。结论:NAs相关各种肌肉骨骼及结缔组织疾病风险信号在药品之间可能存在差别,应重视TDF、ADV及LAM引起骨骼类疾病的风险,加强临床用药监测,对存在骨骼类疾病高风险患者建议优选ETV和TAF。

OBJECTIVE To mine the data of nucleos(t)ide analogues(NAs) related musculoskeletal and connective tissue disorder events based on FDA Adverse Event Report System(FAERS),so as to provide reference for clinical rational drug use.METHODS FAERS data of 23 quarters from the first quarter of 2017 to the third quarter of 2022 were downloaded and screened.After data processing,NAs related musculoskeletal and connective tissue disorder adverse events were extracted and signal detection was performed by using medicines and healthcare products regulatory agency(MHRA)and reporting odds ratio(ROR).RESULTS A total of 22 416 NAs related musculoskeletal and connective tissue disorder events were obtained,including 21 068 reports on tenofovir disoproxil fumarate(TDF),626 reports on adefovir dipivoxil(ADV),426 reports on lamivudine(LAM),127 reports on entecavir(ETV),and 169 reports on tenofovir alafenamide fumarate(TAF) with the detected signals of 34,22,13,2 and 2,respectively.At the high level group term(HLGT) level,the signals of TDF,ADV,LAM and TAF were mainly distributed in skeletal diseases( excluding congenital diseases and fractures),which were 97.33%,67.08%,72.73% and 78.57%,respectively.The signals of ETV were mainly distributed in muscle diseases,accounting for 86.96%.The signals of TDF,ADV and LAM were mainly distributed in metabolic bone diseases such as osteoporosis and osteomalacia,while the signals of TAF and ETV were not involved in metabolic bone diseases.CONCLUSION The potential risks of NAs related musculoskeletal and connective tissue disorders may differ among varieties.It is suggested that more attention should be paid to the skeletal disease events related to TDF,ADV and LAM.The monitoring of clinical drug use should be strengthened to detect and deal with ADE in time.ETV and TAF are recommended for people with high risk of skeletal diseases.