Thyroid-associated ophthalmopathy: Emergence of teprotumumab as a promising medical therapy

Best Pract Res Clin Endocrinol Metab. 2020 Jan;34(1):101383. doi: 10.1016/j.beem.2020.101383. Epub 2020 Jan 31.

Abstract

Thyroid-associated ophthalmopathy (TAO) remains a vexing autoimmune component of Graves' disease that can diminish the quality of life as a consequence of its impact on visual function, physical appearance and emotional well-being. Because of its relative rarity and variable presentation, the development of highly effective and well-tolerated medical therapies for TAO has been slow relative to other autoimmune diseases. Contributing to the barriers of greater insight into TAO has been the historical absence of high-fidelity preclinical animal models. Despite these challenges, several agents, most developed for treatment of other diseases, have found their way into consideration for use in active TAO through repurposing. Among these, teprotumumab is a fully human inhibitory monoclonal antibody against the insulin-like growth factor I receptor. It has shown remarkable effectiveness in moderate to severe, active TAO in two completed multicenter, double masked, and placebo controlled clinical trials. The drug exhibits a favorable safety profile. Teprotumumab has recently been approved by the U.S. F.D.A, and may rapidly become the first line therapy for this disfiguring and potentially blinding condition.

Keywords: autoimmune; biological agents; graves' disease; insulin-like growth factor-I receptor; monoclonal antibodies; teprotumumab.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Graves Disease / drug therapy
  • Graves Disease / immunology
  • Graves Ophthalmopathy / drug therapy*
  • Graves Ophthalmopathy / immunology
  • Graves Ophthalmopathy / metabolism
  • Humans
  • Immunotherapy / methods
  • Immunotherapy / trends
  • Quality of Life
  • Receptor, IGF Type 1 / antagonists & inhibitors
  • Receptor, IGF Type 1 / immunology
  • Receptor, IGF Type 1 / metabolism
  • Therapies, Investigational / methods*
  • Therapies, Investigational / trends

Substances

  • Antibodies, Monoclonal, Humanized
  • Receptor, IGF Type 1
  • teprotumumab