Chen Heng, He Gefei, Huang Juanjuan, Hu Lin, Ma Junlong
Department of Pharmacy, The First Hospital of Changsha, Changsha, Hunan, China.
Center of Clinical Pharmacology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Front Immunol. 2024 Dec 17;15:1495137. doi: 10.3389/fimmu.2024.1495137. eCollection 2024.
Antibody-drug conjugates (ADCs) are increasingly utilized in patients with solid tumors and hematologic malignancies. However, the adverse ocular toxicity induced by ADCs has not been comprehensively evaluated in real-world clinical settings.
Data from April 2019 to March 2024 based on the FDA Adverse Event Reporting System (FAERS) were extracted and analyzed. Disproportionality analysis was used to evaluate the association between ADCs and ocular adverse events (AEs). The median time to onset (TTO) of various ADCs was compared.
A comprehensive analysis identified 2,686 ocular AEs associated with ADCs. Among these, Tisotumab vedotin had the most positive signals at the preferred terms (PTs) level, followed by trastuzumab emtansine and enfortumab vedotin. In contrast, gemtuzumab ozogamicin demonstrated minimal ocular toxicity signals. Cluster analysis revealed that ADC-related ocular toxicities predominantly manifested as corneal disorders or ocular neuromuscular disorders. The median onset of ocular toxicity varied considerably, with enfortumab vedotin showing the earliest median onset at 12.5 days.
Our study demonstrates the association between ADCs and ocular AEs based on real-world data, providing valuable guidance for clinicians when prescribing ADCs. And we found some important safety signals that have not been mentioned in the label or previous studies.
抗体药物偶联物（ADCs）越来越多地应用于实体瘤和血液系统恶性肿瘤患者。然而，ADCs引起的眼部不良毒性在真实世界临床环境中尚未得到全面评估。
提取并分析了2019年4月至2024年3月基于美国食品药品监督管理局不良事件报告系统（FAERS）的数据。采用比例失衡分析来评估ADCs与眼部不良事件（AEs）之间的关联。比较了各种ADCs的中位起效时间（TTO）。
一项综合分析确定了2686例与ADCs相关的眼部AEs。其中，维迪西妥单抗在首选术语（PTs）水平上的阳性信号最强，其次是曲妥珠单抗-美坦新和恩扎妥昔单抗。相比之下，吉妥珠单抗奥唑米星显示出最小的眼部毒性信号。聚类分析表明，ADCs相关的眼部毒性主要表现为角膜疾病或眼部神经肌肉疾病。眼部毒性的中位起效时间差异很大，恩扎妥昔单抗的中位起效时间最早，为12.5天。
我们的研究基于真实世界数据证明了ADCs与眼部AEs之间的关联，为临床医生开具ADCs处方时提供了有价值的指导。并且我们发现了一些在标签或先前研究中未提及的重要安全信号。
