Zong Yuan, Qiu Shuang, Yang Mingming, Zhang Jing, Zou Yaru, Jing Yuxin, Ohno-Matsui Kyoko, Kamoi Koju
Department of Ophthalmology, Zhongshan Torch Development Zone People's Hospital, Zhongshan 528436, China.
Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8510, Japan.
Antibodies (Basel). 2025 Jun 30;14(3):55. doi: 10.3390/antib14030055.
Thyroid eye disease (TED) is a complex autoimmune disorder characterized by orbital inflammation and tissue remodeling. Teprotumumab, a fully human monoclonal antibody targeting insulin-like growth factor-1 receptor (IGF-1R), represents a significant breakthrough in TED treatment. This review comprehensively analyzes the therapeutic role of teprotumumab in TED management. Mechanistically, teprotumumab inhibits the IGF-1R/TSHR signaling complex, thereby reducing orbital fibroblast differentiation and inflammatory responses. Phase II and III clinical trials have demonstrated its remarkable efficacy in reducing proptosis and improving clinical activity scores, with the benefits extending to both active and chronic TED cases. Real-world studies have validated these findings further and expanded its potential applications to various clinical scenarios, including dysthyroid optic neuropathy and steroid-resistant cases. However, several challenges remain. These include treatment-related adverse effects such as hyperglycemia and hearing impairment, with emerging evidence suggesting ethnic variations in susceptibility. The high cost of treatment poses significant accessibility barriers, while limited long-term follow-up data and potential disease recurrence necessitate further investigation. This review synthesizes the current evidence to inform clinical decision-making and highlights areas requiring additional research to optimize teprotumumab's therapeutic application in TED management.
甲状腺眼病（TED）是一种复杂的自身免疫性疾病，其特征为眼眶炎症和组织重塑。替普妥单抗是一种靶向胰岛素样生长因子-1受体（IGF-1R）的全人单克隆抗体，代表了TED治疗的重大突破。本综述全面分析了替普妥单抗在TED管理中的治疗作用。从机制上讲，替普妥单抗抑制IGF-1R/TSHR信号复合物，从而减少眼眶成纤维细胞分化和炎症反应。II期和III期临床试验已证明其在减少眼球突出和改善临床活动评分方面具有显著疗效，其益处适用于活动性和慢性TED病例。真实世界研究进一步验证了这些发现，并将其潜在应用扩展到各种临床场景，包括甲状腺功能异常性视神经病变和类固醇抵抗病例。然而，仍存在一些挑战。这些包括与治疗相关的不良反应，如高血糖和听力障碍，新出现的证据表明易感性存在种族差异。治疗费用高昂构成了重大的可及性障碍，而长期随访数据有限和疾病可能复发需要进一步研究。本综述综合了当前证据以指导临床决策，并强调了需要进一步研究以优化替普妥单抗在TED管理中的治疗应用的领域。
