基于FAERS数据库的地舒单抗肌肉骨骼毒性数据挖掘  

Musculoskeletal disorder of denosumab based on FAERS database mining

作　　者：熊学惠 刘芳[2] 潘凌[2] 席宇飞[1] 范国荣[1] 谈仪炯 XIONG Xue-hui;LIU Fang;PAN Ling;XI Yu-fei;FAN Guo-rong;TAN Yi-jiong(Department of Clinical Pharmacy,Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,SHANGHAI 200080,China;Department of Endocrinology&Metabolism,Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,SHANGHAI 200080,China)

机构地区：[1]上海交通大学医学院附属第一人民医院临床药学科,上海200080 [2]上海交通大学医学院附属第一人民医院内分泌代谢科,上海200080

出　　处：《中国新药与临床杂志》2022年第12期759-766,共8页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家自然科学基金面上项目(82170827);上海市自然科学基金(22ZR1450100)。

摘　　要：目的挖掘和评价地舒单抗相关肌肉骨骼毒性(MSD)的不良反应(ADR)信号。方法采用比例报告比(PRR)和报告比值比(ROR)对2010年6月至2022年3月美国食品和药物管理局不良事件报告系统(FAERS)中接收的地舒单抗相关MSD进行ADR信号挖掘分析,并对其导致严重不良事件危险因素进行Logistic回归分析。结果筛选出地舒单抗为首要怀疑药物的MSD不良事件报告共20655份。报告患者为女性的有15492份(占75.00%)、男性2777份(占13.44%)。报告患者的主要年龄范围为50~74岁,共6551份(占31.72%)。严重不良事件报告2424份(占11.74%)。信号强度排名前20位的首选术语中未在说明书中出现的信号共10个,包括脊柱畸形、颌骨外生性骨疣、颌骨外露等。Logistic回归分析显示,使用60 mg地舒单抗的患者发生严重不良事件风险与性别(OR=0.665,95%CI:0.511~0.866)、年龄(OR=1.261,95%CI:1.122~1.417)、合并用药数量(OR=1.817,95%CI:1.680~1.966)显著相关(P<0.05);而使用120 mg地舒单抗的患者其风险仅与合并用药数量(OR=1.534,95%CI:1.401~1.680)显著相关(P<0.05)。结论使用地舒单抗时应关注MSD风险,说明书中未提及的脊柱畸形、颌骨外生性骨疣、颌骨外露等新的ADR应引起重视,男性、高龄、合并用药数量多是MSD致严重不良事件的高风险因素,应加强药学监护。AIM To explore and evaluate the adverse drug reaction(ADR)signals of denosumab-related musculoskeletal disorder(MSD),to provide evidence for clinical rational and safe drug use.METHODS ADR signals of denosumab-related MSD received in the U.S.Food and Drug Adminstration Adverse Event Reporting System(FAERS)from June 2010 to March 2022 were extracted by proportional reporting ratio(PRR)and reporting odds ratio(ROR).Logistic regression analysis was conducted on the risk factors for MSD serious adverse events.RESULTS A total of 20655 MSD adverse event reports with denosumab as the primary suspected drug were collected.15492 cases(75.00%)were female and 2777 cases(13.44%)were male.The dominant age group was from 50 to 74 years old,with a total of 6551 cases(31.72%).There were 2424 serious adverse event reports(11.74%).Among the top 20 preferred terms(PTs)in signal intensity,10 signals that were not listed in the instructions,including spinal deformity,exostosis of jaw,exposed bone in jaw,etc.Logistic regression analysis showed that the risk of serious adverse events in patients receiving 60 mg denosumab was significantly associated with gender(OR=0.665,95%CI:0.511 to 0.866),age(OR=1.261,95%CI:1.122 to 1.417)and number of concomitant drugs(OR=1.817,95%CI:1.680 to 1.966,P<0.05),while the risk in patients receiving 120 mg denosumab was only significantly related with number of concomitant drugs(OR=1.534,95%CI:1.401 to 1.680,P<0.05).CONCLUSION Attentions should be paid to the risk of MSD when using denosumab,especially those new ADR signals,such as spinal deformity,exostosis of jaw,exposed bone in jaw,etc.Male,elderly and more combined drugs are high risk factors for serious adverse events caused by MSD,and pharmaceutical care should be strengthened.

关 键 词：地舒单抗 肌肉骨骼毒性 不良反应信号 数据挖掘 

分 类 号：R683[医药卫生—骨科学] R969.3[医药卫生—外科学]