Teprotumumab as a Breakthrough in Thyroid Eye Disease Therapy: A Comprehensive Review

Background. Thyroid Eye Disease (TED) is a complex autoimmune condition associated with Graves' disease, causing disfigurement, visual impairment, and reduced quality of life. For decades, options were limited to non-specific anti-inflammatory treatments like glucocorticosteroids and radiotherapy, often failing to address symptoms like proptosis and diplopia. Identifying the insulin-like growth factor-1 receptor (IGF-1R) as a driver of TED pathophysiology led to targeted therapies.Aim. This study reviews teprotumumab as a breakthrough TED therapy, analyzing its mechanism, efficacy, and place in treatment algorithms relative to traditional methods.Material and methodsA literature review was conducted using databases (PubMed, Embase, ClinicalTrials.gov) for articles up to November 2025. Analysis prioritized pivotal trials (OPTIC, OPTIC-X), meta-analyses, and reviews focusing on TED pathophysiology and IGF-1R inhibition.Results. TED pathogenesis involves crosstalk between TSHR and IGF-1R on orbital fibroblasts, triggering inflammation and adipogenesis. While traditional treatments offer limited relief with side effects, teprotumumab, the first FDA-approved IGF-1R inhibitor, targets these mechanisms. Clinical data shows superior efficacy in reducing proptosis and improving diplopia compared to palliative care.Conclusions. Teprotumumab is a breakthrough in TED management, shifting from symptomatic to targeted disease modification. By addressing orbital remodeling causes, it offers distinct advantages over traditional therapies, fulfilling a major unmet need.