Liu Chuanya, Li Shangze, Wang Ziyi, Li Zhifu, Fang Zhou, Zhang Yuan, Gao Yu
Department of Ophthalmology, The First Affiliated Hospital (Shanghai Changhai Hospital), Naval Medical University, Shanghai, China.
Department of Orthopedics, Changzhou Medical District, No. 904 Hospital of PLA Joint Logistic Support Force, Changzhou, China.
BMC Pharmacol Toxicol. 2025 Apr 12;26(1):82. doi: 10.1186/s40360-025-00902-6.
Faricimab is a bispecific antibody targeting vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), offering a novel therapeutic approach for ocular diseases. However, its long-term safety profile remains under evaluation. This study analyzes its adverse events (AEs) using the U.S. FDA Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER).
AEs from FAERS (2004-2024) and JADER (2004-2024) were analyzed using disproportionality algorithms. Subgroup analyses assessed differences by age and sex. AE onset time was also assessed.
Several newly identified adverse events (AEs) were observed, including macular ischemia, keratic precipitates, and optic nerve injury, with strong safety signals detected in both FAERS and JADER. For instance, macular ischemia showed a high association with faricimab use (ROR = 260.46), suggesting a potential risk of retinal circulation impairment. Similarly, keratic precipitates (ROR = 739.65) indicate a notable inflammatory response. All these findings highlight the need for closer monitoring of ocular complications, particularly in high-risk patient groups. The FAERS database mainly reported retinal occlusive vasculitis, ocular vasculitis, and keratic precipitates, while JADER predominantly featured retinal occlusive vasculitis and retinal vascular occlusion. Sex-based differences indicated a higher risk of inflammatory AEs in females (e.g., uveitis and eye inflammation) and a greater incidence of retinal vascular events in males (e.g., retinal vasculitis). Age-related differences showed that older patients (≥65 years) had lower inflammatory AE risks but were more prone to optic nerve damage and retinal atrophy, while younger patients (<65 years) exhibited a higher risk of vitreous hemorrhage and cataracts.
This study identified previously unreported safety signals, suggesting the need for potential updates to faricimab's safety labeling. Faricimab's dual-target mechanism presents unique safety concerns. Clinicians should monitor ocular inflammation and vascular complications, particularly in younger males and Asian patients. Further studies using real-world data are needed to validate these findings.
法西单抗是一种靶向血管内皮生长因子（VEGF）和血管生成素-2（Ang-2）的双特异性抗体，为眼部疾病提供了一种新的治疗方法。然而，其长期安全性仍在评估中。本研究使用美国食品药品监督管理局不良事件报告系统（FAERS）和日本药品不良事件报告（JADER）分析其不良事件（AE）。
使用不成比例算法分析来自FAERS（2004 - 2024年）和JADER（2004 - 2024年）的不良事件。亚组分析评估了年龄和性别的差异。还评估了不良事件的发病时间。
观察到了几种新发现的不良事件，包括黄斑缺血、角膜后沉着物和视神经损伤，在FAERS和JADER中均检测到了强烈的安全信号。例如，黄斑缺血与法西单抗的使用高度相关（风险比[ROR]=260.46），表明存在视网膜循环障碍的潜在风险。同样，角膜后沉着物（ROR = 739.65）表明有明显的炎症反应。所有这些发现凸显了对眼部并发症进行密切监测的必要性，特别是在高危患者群体中。FAERS数据库主要报告视网膜闭塞性血管炎、眼部血管炎和角膜后沉着物，而JADER主要特征为视网膜闭塞性血管炎和视网膜血管闭塞。基于性别的差异表明，女性发生炎症性不良事件的风险更高（如葡萄膜炎和眼部炎症），男性发生视网膜血管事件的发生率更高（如视网膜血管炎）。与年龄相关的差异表明，老年患者（≥65岁）发生炎症性不良事件的风险较低，但更容易发生视神经损伤和视网膜萎缩，而年轻患者（<65岁）发生玻璃体出血和白内障的风险较高。
本研究发现了先前未报告的安全信号，表明可能需要更新法西单抗的安全标签。法西单抗的双靶点机制带来了独特的安全问题。临床医生应监测眼部炎症和血管并发症，特别是在年轻男性和亚洲患者中。需要使用真实世界数据进行进一步研究以验证这些发现。
