基于美国FDA不良事件报告系统调研克唑替尼在儿童肿瘤治疗中的安全性

Safety investigation of crizotinib in pediatric oncology therapy based on the FDA Adverse Event Reporting System database

目的基于美国食品药品监督管理局(FDA)不良事件报告系统(FAERS),挖掘与分析克唑替尼治疗儿童肿瘤的不良反应信号,为临床安全合理用药提供参考。方法基于2011年第3季度至2022年第3季度的FAERS数据,检索克唑替尼治疗儿童肿瘤的病例。采用比例失衡法中的报告比值比(ROR)法和比例报告比法(PRR)对药物不良事件(ADE)报告进行不良反应信号检测。结果共获取克唑替尼治疗儿童肿瘤的病例103例,首选术语(PT)312个,累及系统器官分类(SOC)20个,主要集中在胃肠系统疾病、各类检查、全身性疾病及给药部位各种反应、感染及侵染类疾病与代谢及营养类疾病等。挖掘出脓毒症、分泌物排出、缺氧等新的PT,还有耳及迷路类疾病、内分泌系统疾病、免疫系统疾病与各类损伤、中毒及操作并发症等新的SOC。报告频数位列前五的PT依次为中性粒细胞减少症、腹泻、死亡、恶心和中性粒细胞计数降低。信号强度位列前五的PT依次为食管炎、分泌物排出、中性粒细胞计数降低、缺氧和视觉损害。结论基于FAERS的药物警戒研究,应对儿童使用克唑替尼发生频数较高以及新发的不良事件予以重视。在开始使用克唑替尼前,儿童患者应接受眼科基线检查,并在随后治疗中监测眼毒性。

AIM To mine and analyze the adverse event signals of crizotinib for the treatment of pediatric tumors based on the U.S.FDA Adverse Event Reporting System(FAERS)database,providing reference for the safe and rational use of drugs in clinical practice.METHODS Cases of crizotinib for pediatric patients were retrieved based on FAERS data from the third quarter of 2011 to the third quarter of 2022.The reporting odds ratio(ROR)method and the proportional reporting ratio(PRR)from disproportionality analysis were used to detect the signal of adverse drug events(ADE)reports.RESULTS A total of 103 cases of crizotinib in treating pediatric tumors with 312 preferred terminologies(PT)involving 20 system organ classifications(SOC)were obtained.The main focus wss on gastrointestinal diseases,various examinations,systemic diseases and various reactions at the site of administration,infections and infectious diseases,and metabolic and nutritional diseases.New PT such as sepsis,discharge of secretions,hypoxia were uncovered,as well as new SOC such as ear and vagus disorders,endocrine system disorders,immune system disorders with various types of injury,poisoning,and operational complications.The top 5 most frequently reported PT were neutropenia,diarrhea,death,nausea,and decreased neutrophil count.The top 5 PT in terms of signal strength were esophagitis,discharge of secretions,decreased neutrophil count,hypoxia,and visual impairment.CONCLUSION Based on pharmacovigilance studies of the FAERS database,attention should be paid to the high frequency and newly emerged adverse events that occured in children using crizotinib.Prior to initiation of crizotinib,pediatric patients should receive a baseline ophthalmologic examination and be monitored for ocular toxicity during subsequent therapy.