Teprotumumab for Thyroid Eye Disease: Mechanism, Clinical Efficacy, and Current Challenges

Abstract

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.

Keywords: Graves’ disease; clinical efficacy; insulin-like growth factor-1 receptor; orbital fibroblasts; teprotumumab; thyroid eye disease.

Figure 1

Pathophysiology of thyroid eye disease (TED).