-associated ophthalmopathy, a condition commonly associated with Graves’
disease, remains inadequately treated. Current medical therapies, which primarily
consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition
of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic
strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy
Current treatments are inconsistently beneficial and often associated with side effects,
- Previous clinical trials suggest that high dose glucocorticoids, alone3-5 or with radiotherapy can reduce inflammation-related signs and symptoms in patients with active ophthalmopathy.
- However, glucocorticoids and orbital radiotherapy minimally affect proptosis and can cause dose-limiting adverse reactions.5 In many patients
- in patients with Graves’ disease, Immunoglobulins that activate insulin-like growth factor I (IGF-I) receptor (IGF-IR) signaling have been detected
- IGF-I synergistically enhances the actions of thyrotropin IGF-IR is a membraneespanning tyrosine kinase receptor with roles in development and metabolism
- IGF-IR is overexpressed by orbital fibroblasts18 and by T cells and B cells in persons with Graves’ disease.
- (IGF-I) regulates immune function and thus might be targeted therapeutically in autoimmune diseases.
Mechanism of Action
Teprotumumab-trbw’s mechanism of action in patients with Thyroid Eye Disease has not been fully characterized. Teprotumumab-trbw binds to IGF-1R and blocks its activation and signaling.