基于FAERS对4种免疫抑制剂高血糖风险的挖掘与分析

Excavation and analysis of hyperglycemia risk of 4 immunosuppressive agents based on FAERS

目的基于美国FDA不良事件报告系统(FAERS),挖掘并评价常用免疫抑制剂他克莫司、环孢素、西罗莫司和依维莫司相关的高血糖症/新发糖尿病信号,为临床合理用药提供参考。方法利用ICH国际医学用语词典(MedDRA)查询SMQ术语集“hyperglycaemia/new onset diabetes mellitus”狭义范围内的首选术语(PT),在FAERS中提取2013年第1季度至2022年第4季度上述药物的相关病例,数据去重后,采用报告比值比(ROR)法和比例报告比(PRR)法对高血糖症/新发糖尿病信号进行检测与分析。结果共提取到ADE报告736份,其中肾移植报告例数最多(占38.99),男性占54.30%,患者年龄主要为45~64岁,严重ADE占57.06%。ROR法和PRR法同时检出24个可疑信号,其中他克莫司对14个,依维莫司对5个,西罗莫司3个,环孢素2个。不同免疫抑制剂检出的可疑信号类型和强度均存在一定差异。结论临床上常用的4种免疫抑制剂均存在高血糖风险。与其他3种药物相比,他克莫司与高血糖相关性较强,提示临床应用时应注意高血糖相关不良反应。

AIM To excavate and evaluate tacrolimus,cyclosporine,sirolimus,and everolimus associated with hyperglycemia/new-onset diabetes based on American FDA Event Reporting System(FAERS),and to provide reference for rational drug use in clinical practice.METHODS The preferred term(PT)within the narrow sense of"hyperglycemia/new onset diabetes mellitus"in the SMQ term set was queried using the ICH International Dictionary of Medical Terms(MedDRA),and cases related to the above drugs were extracted in FAERS from the first quarter of 2013to the fourth quarter of 2022.After data deduplication,hyperglycemia/new-onset diabetes signal detection and analysis were performed using the reporting odds ratio(ROR)method and proportional reporting ratio(PRR)method.RESULTS A total of 736 ADE reports were extracted,of which renal transplantation accounted for 38.99%,male accounted for 54.30%,the age of patients was mainly 45-64 years old,and severe ADE accounted for 57.06%.The results of signal retrieval showed that 24 suspicious signals were detected by the PRR and ROR method at the same time,of which 14suspicious signals were detected by tacrolimus,5 suspicious signals were detected by everolimus,3 suspicious signals were detected by sirolimus,and 2 suspicious signals were detected by cyclosporine.The types and intensities of signals differed among 4 immunosuppressive agents.CONCLUSION All 4 immunosuppressive agents commonly used in clinical practice carry the risk of hyperglycemia.Compared with other drugs,tacrolimus has shown a strong statistical correlation with hyperglycemia.It is suggested that attention should be paid to the hyperglycemia-related adverse reactions in clinical application.