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Teprotumumab: The First Approved Biologic for Thyroid Eye Disease

Thyroid eye disease (TED) is a common orbital disease that occurs in parallel with systemic Graves disease (GD). Up to 50% of patients with GD may show signs of TED, which can also occur in euthyroid or hypothyroid states.1 In the last 2 decades, significant progress has been achieved in delineating the pathophysiology of TED. Researchers first determined that fibrocytes are a key cell in the inflammatory cascade leading to a complex auto-immune phenomenon targeting the orbital tissues. Clinical manifestations of TED often include soft tissue signs such as periorbital edema, eyelid retraction, and conjunctival injection while more severe signs include proptosis, diplopia, and extraocular muscle enlargement rarely leading to compressive optic neuropathy.2–4 The natural course of TED is frequently described as a curve with an early active inflammatory phase followed by a quiescent phase. Traditionally, surgical care has been directed toward correcting the often disfiguring sequelae during the quiescent phase except in severe cases where urgent intervention is necessary. Medical therapy has been limited to intravenous and oral steroids to blunt the inflammatory response, and off-label uses of anti-inflammatory medications including methotrexate, rituximab, and tocilizumab.5 Radiation therapy has also been used as a treatment modality for active-phase disease with limited conflicting clinical trial data on its efficacy.1 Recent research has highlighted the role of the insulin-like growth factor axis in the pathogenesis of TED. Insulin-like growth factors (IGF-I and IGF-II), their binding proteins (IGFBPs) and receptors (IGF-IR and IGF-IIR) play significant roles in normal development, metabolism, and regulation of immunity.6 Importantly, this pathway has also been implicated in the development of diseases including metabolic disorders, autoimmune disease, and tumorigenesis. As such, researchers have