基于FAERS的地舒单抗安全警戒信号挖掘与评价

基于FAERS数据库挖掘安全警戒信号，分析评估地舒单抗潜在不良反应信号,为其临床使用提供一定参考依据。方法 通过Openvigil 2.1访问 FAERS 数据库，将地舒单抗作为主要药物，检索自该药首次上市时间（2010年5月—2021年9月）的数据，获得与地舒单抗相关的不良事件报告记录。使用报告比值比法（ROR）和贝叶斯置信度递进神经网络法（BCPNN）筛选地舒单抗安全警戒信号，挖掘潜在的不良反应，并通过工具BioPortal对不良事件信号挖掘结果进行系统分类，通过判断信号间置信区间的变化，发现与药物不良事件关联性较大的信号。结果 从FAERS数据库中收集到270503份不良反应事件（ADE）报告，根据ROR法和BCPNN法共得到343个不良事件信号，通过信号间同义合并、剔除与药物无关的信号后，得到316个不良事件信号。地舒单抗的不良事件系统分类主要为肌肉骨骼和结缔组织疾病、医学检查、胃肠道疾病。FAERS数据库的信号挖掘结果发现，高风险且说明书中未收录的安全警戒信号包括颞下颌关节综合征、下颌脓肿、雌激素缺乏症、血液甲状旁腺激素增加，计算高风险信号的置信区间显示颞下关节综合征较有可能发展成为新的不良反应；另外，也发现种植体周围炎为具有临床意义的可疑警戒信号，但有待进一步观察研究。结论 基于FAERS数据库的信号挖掘结果提示临床应规范使用地舒单抗，治疗期间需警惕患者是否出现颞下颌关节综合征、下颌脓肿、雌激素缺乏症、血液甲状旁腺激素增加等不良反应事件，以便尽早发现尽早处理，从而有效降低临床用药风险

Safety warning signal mining and evaluation of desomumab based on FAERS

Safety warning signals were mined based on FAERS database to analyze and evaluate potential adverse reaction signals of desomumab, providing certain reference for clinical use of desomumab in the future. Methods Using Openvigil 2.1 to access the FAERS database, denosumab as the primary drug was retrieved from the time of the drug''s debut, May 2010 to September 2021, to obtain a record of reported adverse events related to denosumab. Report ratio method (ROR) and Bayesian confidence progressive neural network method (BCPNN) were used to screen safety warning signals of desomumab to mine potential adverse reactions. The mining results of adverse event signals were systematically classified by the tool BioPortal, and the changes of confidence intervals between signals were determined. Signals associated with adverse drug events were found. Results 270503 adverse event (ADE) reports were collected from the FAERS database, and a total of 343 adverse event signals were obtained according to ROR and BCPNN, and 316 adverse event signals were obtained by synthetically-merging and eliminating drug-unrelated signals. The systematic classification of adverse events for disumab mainly included musculoskeletal and connective tissue diseases, medical examination, and gastrointestinal diseases. The signal mining results of FAERS database found that high-risk safety warning signals not included in the manual included temporomandibular joint syndrome, mandibular abscess, estrogen deficiency, and increased blood parathyroid hormone. Confidence intervals calculated for high-risk signals showed that subtemporal joint syndrome was more likely to develop into new adverse reactions. In addition, peri-implant inflammation was also found to be a suspicious warning signal of clinical significance, but it needs further observation and study.Conclusion The signal mining results based on the FAERS database suggest that the clinical use of disumab should be standardized. During treatment, patients should be alert to the occurrence of temporomandibular joint syndrome, mandibular abscess, estrogen deficiency, blood parathyroid hormone increase and other adverse events, so as to detect and deal with them as early as possible, so as to effectively reduce the risk of clinical drug use