贝伐珠单抗应用于眼器官疾病的安全信号检测与分析

目的：挖掘贝伐珠单抗治疗眼器官疾病的药品不良事件（ADE）信号，为其眼部超说明书用药管理提供参考。方法：采用报告比值比法（ROR）结合压缩估计对美国不良反应数据库2010第1季度~2021年第1季度中适应症为眼器官疾病的贝伐珠单抗报告进行数据挖掘和安全信号检测。结果：共得到贝伐珠单抗相关的8056个报告，涉及2431份病例，病例数位列前5位的适应症为：年龄相关性黄斑变性、糖尿病性视网膜病变、视网膜静脉阻塞、黄斑水肿、脉络膜新生血管。其中女性（45.37%）多于男性（37.15%）且老年患者居多。总体共得119个ADE信号，涉及18个系统/器官，主要是眼器官。报告数及信号强度均在前30的信号中，眼内炎、失明、玻璃体飞蛾症、视网膜剥离、眼部感染发生最多；脑血管意外、心肌梗死、神经系统病变、动脉血栓形成是死亡风险高且报告数/信号强度在前30的信号。结论：贝伐珠单抗治疗眼器官疾病的ADE信号集中在眼部，可造成不同程度的视力损伤，而生命威胁大的事件多在眼外器官/系统，临床对其在眼病的超适应症使用应更为慎重且应严格管理。

Detection and Analysis of Safety Signals for Bevacizumab in Ocular Organ Diseases

Objective: To mine adverse drug event (ADE) signals in bevacizumab for ocular organ diseases and provide reference for ocular off label use management. Methods: By report odds ratio (ROR) combined with compression estimation algorithm, data-mining and safety signal detection were employed for bevacizumab''s reports with indications of ocular organ diseases from American Adverse Events Reporting System during 1Q 2010 to 1Q 2021. Results: A total of 8056 bevacizumab-related reports were obtained, involving 2431 cases. The main indications in the cases were age-related macular degeneration, diabetic retinopathy, retinal vein occlusion, macular edema and choroidal neovascularization. Patients included in the reports were female (45.37%) more than male (37.15%), predominantly elderly. A total of 119 ADE signals involving 18 systems/organs were detected and mainly focused on ocular organs. Among the top 30 signals in both number of reports and signal intensity, endophthalmitis, blindness, vitreous moth disease, retinal detachment and ocular infection were the most frequently reported. In addition, cerebrovascular accidents, myocardial infarction, neurological lesions and atherothrombosis were with a high risk of death and reported in the top 30 in number or signal intensity. Conclusions: ADE signals of bevacizumab treatment of ocular organ diseases are mostly concentrated in the eyes, which can cause varying degrees of visual impairment, while events with high possibility of life threat are mostly in non-ocular organs/systems, so the clinical off-label use of bevacizumab in eye diseases should be more cautious and strictly managed.