地舒单抗不良反应信号挖掘与分析

目的通过对地舒单抗相关药品不良反应( ADR)进行挖掘与分析，为临床安全合理用药提供依据。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)对美国食品药品监督管理局( FDA)不良事件报告系统(FAERS)中地舒单抗 2010年第 3季度至 2021年第 3季度中发生的 ADR进行挖掘及分析。结果提取到 28 823例以地舒单抗为首要怀疑药物的 ADR报告，共检测出有效信号 256例，涉及 19个器官系统分类。主要涉及肌肉骨骼及结缔组织疾病，胃肠系统疾病，各类检查和感染及侵染类疾病等。在信号强度排序前 50的 ADR中不仅包括说明书中已知的口腔相关 ADR、颌骨坏死、各种类型骨折、外耳道骨坏死、钙离子相关 ADR等。还包括说明书中未提及的 ADR 9种，分别是颌骨外生骨疣，高钙性肾病，免疫介导的肾上腺功能不全，脊柱畸形，纵隔纤维化，甲状腺钙化，椎间盘环形撕裂，下颌骨肿块，关节杂音。结论地舒单抗使用过程中，医务人员不仅要重点关注肌肉骨骼及结缔组织疾病、胃肠系统疾病、各类检查和感染及侵染类疾病，对于信号挖掘发现的新的 ADR也应该提高警惕，积极预防和治疗，以减少 ADR对病人的危害。

Excavation and analysis of ADR signals of denosumab

Objective To provide reference for clinical safety and rational drug use through mining and analyzing the adverse drugreaction (ADR) signals of denosumab.Methods Disproportionality analysis with reporting odds ratio (ROR) and proportional reportingratio (PRR) was used to detect ADR signals of denosumab in the FDA adverse event reporting system (FAERS) from the third quarter of2010 to the third quarter of 2021.Results A total of 28 823 adverse event reports with denosumab as the primary suspected drug wereextracted. Totally 256 signals were detected,involving 19 organ systems, which mainly reported musculoskeletal and connective tissuedisorders, gastrointestinal disorders, and infectious diseases. The top 50 ADRs in signal strength ranking included not only diseases re-ported in the specifications, oral related ADR, osteonecrosis of jaw, various types of fracture, osteonecrosis of external auditory canal,and calcium ion related ADR, but also diseases not mentioned in the specifications, including exostosis of jaw, hypercalcaemic ne-phropathy, immune-mediated adrenal insufficiency, spinal deformity, mediastinal fibrosis, thyroid calcification, intervertebral disc an-nular tear, mandibular mass, and joint noise.Conclusion During the use of denosumab, medical staff should not only focus on muscu-loskeletal and connective tissue disorders, gastrointestinal disorders, and various infectious diseases, but also be alert to new ADRs dis-covered by signal mining, to actively prevent and treat them to reduce the harm caused by ADRs to patients.