【转】贝伐珠单抗不良事件报告分析

仲夏秋夜云

Drug Saf：贝伐珠单抗不良事件报告分析
贝伐珠单抗最初于2004年由美国FDA批准用于治疗转移性结肠癌和其他实体瘤，是第一个血管内皮生长因子(VEGF)抑制剂。但上市前的临床试验检测某些不良事件的能力有限，因此FDA和生产商需要收集和监测上市后的不良事件报告。


研究者从美国FDA不良事件报告系统(AERS)数据库中检索了2004年2月~2009年9月报告的贝伐珠单抗的新不良事件，对贝伐珠单抗和其他所有药物进行失衡分析，通过设置比例报告比(PRR)≥2、观察病例数≥3和卡方检验≥4使其具有统计学意义。通过后续临床评估来确定不良事件的临床相关性，并对相关事件进行分组。


结果显示，一共有523个优先项被失衡报道，其次临床综述中有63项(12%)具有临床意义却未被药物说明书收录。这些优先项被分成15个临床疾病组。在这些临床疾病组中，电解质紊乱的报道数量最多(n=426)，其次是心血管疾病(n=421)、胃肠道反应(n=345)、神经系统紊乱(n=106)和肺炎(n=96)。在敏感性分析中，许多具有临床意义但未标示的疾病仍符合统计学标准，如坏死性筋膜炎、血管壁缺陷、心律失常和传导紊乱，以及自身免疫性血小板减少症。


研究者总结认为，在研究期间共有12,010例关于贝伐珠单抗的不良事件报告，其中94.2%的报告将该药列为可疑药品。失衡分析显示，许多事件已经被确认为贝伐珠单抗的不良事件，但同时也发现了许多临床重要却未被说明书收录的不良事件。如果在未来研究中证实这些不良事件，将会影响临床实践中贝伐珠单抗的应用。
Novel Adverse Events of Bevacizumab in the US FDA Adverse Event Reporting System Database: A Disproportionality Analysis.


Shamloo BK,Chhabra P,Freedman AN,Potosky A,Malin J,Weiss Smith S


Background: Bevacizumab is the first in its class, vascular endothelial growth factor (VEGF) inhibitor that was initially approved by the US FDA in 2004 for the treatment of metastatic colon cancer and other solid tumors. Preapproval clinical trials, particularly for oncology drugs, are limited in their ability to detect certain adverse effects and, therefore, the FDA and pharmaceutical sponsors collect and monitor reports of adverse events (AEs) following approval. Objective: The purpose of this study was to screen the FDA's Adverse Event Reporting System (AERS) database for novel AEs that may be attributed to bevacizumab. Methods: The FDA AERS database was used to identify all AE reports for bevacizumab from February 2004 to September 2009. Disproportionality analysis was conducted for bevacizumab against all other drugs in the background by setting statistical significance at proportional reporting ratio (PRR) ≥2, observed case count ≥3 and chi-square ≥4. Subsequent clinical evaluation was performed to determine the clinical relevance of the findings and to group related events. Results: A total of 523 Preferred Terms (PTs) were disproportionally reported; following clinical review 63 (12%) were found to be both unlabelled and of clinical importance. These PTs were grouped into 15 clinical disorder groups. Among the clinical disorders, electrolyte abnormalities had the greatest number of reports (n?=?426) followed by cardiovascular events (n?=?421), gastrointestinal events (n?=?345), nervous system disorders (n?=?106) and pneumonitis (n?=?96). On sensitivity analysis, a number of clinically important unlabelled disorders, such as necrotizing fasciitis, vessel wall disorders, arrhythmia and conduction disorder and autoimmune thrombocytopenia still met the statistical significance criteria. Conclusions: During the study period, out of 12?010 AE reports mentioning bevacizumab, it was listed as the suspect drug in 94.2% of the reports. Our disproportionality analysis identified many events that are already recognized as AEs of bevacizumab, but it also identified a number of clinically important unlabelled terms, which if confirmed in future studies would have potential implications for use of bevacizumab in clinical practice.