Novel Adverse Events of Bevacizumab in the US FDA Adverse Event Reporting System Database A Disproportionality Analysis
Novel Adverse Events of Bevacizumab in the US FDA Adverse Event Reporting System Database A Disproportionality Analysis
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DOI：
10.2165/11597600-000000000-00000
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发表时间：
2012-01-01
期刊：
影响因子：
4.2
通讯作者：
Smith, Sheila Weiss
中科院分区：
文献类型：
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作者：
Shamloo, Behrooz K.;Chhabra, Pankdeep;Smith, Sheila Weiss
工作背景：贝伐单抗是同类药物中的第一种血管内皮生长因子（VEGF）抑制剂，最初于2004年被美国FDA批准用于治疗转移性结肠癌和其他实体瘤。批准前的临床试验，特别是肿瘤药物，在检测某些不良反应的能力方面受到限制，因此，FDA和制药赞助商在批准后收集和监测不良事件（AE）报告。目的：本研究的目的是筛选FDA的不良事件报告系统（AERS）数据库中可能归因于贝伐单抗的新AE。FDA AERS数据库用于识别2004年2月至2009年9月期间贝伐珠单抗的所有AE报告。通过将统计学显著性设定为比例报告比（PRR）>= 2、观察到的病例计数>= 3和卡方>= 4，对贝伐珠单抗与背景中所有其他药物进行比例失调分析。随后进行临床评价，以确定临床相关性的调查结果和组相关events.Results：共523首选术语（PT）的preventionally报告，临床审查后63（12%）被发现是未标记的和临床重要性。将这些PT分为15个临床疾病组。在临床疾病中，电解质异常的报告数量最多（n=426），其次是心血管事件（n=421）、胃肠道事件（n=345）、神经系统疾病（n=106）和肺炎（n=96）。在敏感性分析中，一些临床上重要的未标记的疾病，如坏死性筋膜炎，血管壁疾病，心律失常和传导障碍和自身免疫性血小板减少症仍然符合统计学意义criteria.Conclusions：在研究期间，12 010例AE报告提到贝伐珠单抗，它被列为可疑药物的94.2%的报告。我们的一致性分析确定了许多已被确认为贝伐珠单抗AE的事件，但也确定了许多临床重要的未标记术语，如果在未来的研究中得到证实，将对贝伐珠单抗在临床实践中的使用产生潜在影响。
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. Pre-approval 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.