Background：Teprotumumab is a human IgG1 monoclonal antibody directed against the insulin-like growth factor 1 receptor IGF1R that is used in the therapy of Graves ophthalmopathy thyroid eye disease. Graves disease is an autoimmune disease associated with autoantibodies, hyperthyroidism and a distinctive form of eye disease marked by ocular inflammation and proptosis causing eye pain, dryness, redness, and swelling which if severe can cause diplopia double-vision and loss of vision. Graves ophthalmopathy is associated with autoantibodies to thyrotropin and hypertrophy of ocular fibroblasts which overexpress the IGF1 receptor. Teprotumumab causes inhibition of IGF1 binding to its receptor and preventing cell activation. IGF1 is a potent modulator of cell growth and inhibitor of programmed cell death, acting via the PI3K-AKT-mTOR pathway. The inhibition of IGF1 signaling decreases fibroblast proliferation and hypertrophy.
