Mao KaiLi, Chen Ping, Sun HuaYu, Zhong SongYang, Zheng HongLiang, Xu LuYao
Department of Pharmacy, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, China.
Front Pharmacol. 2024 Aug 20;15:1425617. doi: 10.3389/fphar.2024.1425617. eCollection 2024.
Antibody-drug conjugates (ADCs) have emerged as the focus and hotspots in the cancer field, yet the accompanying ocular toxicity has often been underestimated. We aimed to comprehensively and comparatively analyze the risk of ocular toxicity associated with various ADCs using the FDA Adverse Event Reporting System (FAERS) database.
Data were extracted from the FAERS database from Q3 2011 to Q3 2023. We analyzed the clinical characteristics of ADCs-related ocular adverse events (AEs). These data were further mined by proportional analysis and Bayesian approach to detect signals of ADCs-induced ocular AEs. Moreover, the time to onset of ocular toxicity was also evaluated.
A total of 1,246 cases of ocular AEs were attributed to ADCs. Ocular toxicity signals were observed in patients treated with belantamab mafodotin, brentuximab vedotin, enfortumab vedotin, mirvetuximab soravtansine, sacituzumab govitecan, trastuzumab deruxtecan, and trastuzumab emtansine. Of these, belantamab mafodotin, trastuzumab emtansine, and mirvetuximab soravtansine, whose payloads are microtubule polymerization inhibitors, were more susceptible to ocular toxicity. The ten most common ADCs-related ocular AEs signals are keratopathy [ROR = 1,273.52, 95% CI (1,129.26-1,436.21)], visual acuity reduced [ROR = 22.83, 95% CI (21.2-24.58)], dry eye [ROR = 9.69, 95% CI (8.81-10.66)], night blindness [ROR = 259.87, 95% CI (228.23-295.89)], vision blurred [ROR = 1.78, 95% CI (1.57-2.02)], photophobia [ROR = 10.45, 95% CI (9.07-12.05)], foreign body sensation in eyes [ROR = 23.35, 95% CI (19.88-27.42)], ocular toxicity [ROR = 144.62, 95% CI (117.3-178.32)], punctate keratitis [ROR = 126.21, 95% CI (101.66-156.69)], eye disorder [ROR = 2.71, 95% CI (2.21-3.32)]. In terms of onset time, sacituzumab govitecan displayed an earlier onset of 21 days, while trastuzumab deruxtecan exhibited the latest onset of 223 days.
ADCs may increase the risk of ocular toxicity in cancer patients, leading to serious mortality. With the widespread application of newly launched ADCs, combining the FAERS data with other data sources is crucial for monitoring the ocular toxicity of ADCs. In addition, novel ocular toxicity signals not documented in product labeling were detected. Further research will be necessary to validate our findings in the future.
抗体药物偶联物（ADCs）已成为癌症领域的焦点和热点，但其伴随的眼部毒性往往被低估。我们旨在使用美国食品药品监督管理局不良事件报告系统（FAERS）数据库，全面且比较性地分析与各种ADCs相关的眼部毒性风险。
从2011年第三季度至2023年第三季度的FAERS数据库中提取数据。我们分析了与ADCs相关的眼部不良事件（AEs）的临床特征。通过比例分析和贝叶斯方法对这些数据进行进一步挖掘，以检测ADCs诱发眼部AEs的信号。此外，还评估了眼部毒性的发病时间。
共有1246例眼部AEs归因于ADCs。在接受贝兰他单抗马福多汀、本妥昔单抗、恩沃利单抗、米尔维妥昔单抗索拉凡坦辛、戈沙妥珠单抗、曲妥珠单抗德卢替康和曲妥珠单抗恩坦辛治疗的患者中观察到眼部毒性信号。其中，payload为微管聚合抑制剂的贝兰他单抗马福多汀、曲妥珠单抗恩坦辛和米尔维妥昔单抗索拉凡坦辛更容易发生眼部毒性。十个最常见的与ADCs相关的眼部AEs信号为角膜病[风险比（ROR）=1273.52，95%置信区间（CI）（1129.26 - 1436.21）]、视力下降[ROR = 22.83，95% CI（21.2 - ）]、干眼[ROR = 9.69，95% CI（8.81 - 10.66）]、夜盲[ROR = 259.87，95% CI（228.23 - 295.89）]、视力模糊[ROR = 1.78，95% CI（1.57 - 2.02）]、畏光[ROR = 10.45，95% CI（9.07 - 12.05）]、眼内异物感[ROR = 23.35，95% CI（19.88 - 27.42）]、眼部毒性[ROR = 144.62，95% CI（117.3 - 178.32）]、点状角膜炎[ROR = 126.21，95% CI（101.66 - 156.69）]、眼部疾病[ROR = 2.71，95% CI（2.21 - 3.32）]。在发病时间方面，戈沙妥珠单抗的发病时间较早，为21天，而曲妥珠单抗德卢替康的发病时间最晚，为223天。
ADCs可能会增加癌症患者眼部毒性的风险，导致严重的死亡率。随着新推出的ADCs的广泛应用，将FAERS数据与其他数据源相结合对于监测ADCs的眼部毒性至关重要。此外，还检测到了产品标签中未记录的新型眼部毒性信号。未来需要进一步的研究来验证我们的发现。
原文中“视力下降[ROR = 22.83，95% CI（21.2 - ）]”括号内右括号后缺少数据，翻译时保留原文格式。
