Teprotumumab as a Novel Therapy for Thyroid-Associated Ophthalmopathy

Terry J Smith

doi:10.3389/fendo.2020.610337

Abstract

Thyroid-associated ophthalmopathy (TAO) has remained a vexing and poorly managed autoimmune component of Graves’ disease where the tissues surrounding the eye and in the upper face become inflamed and undergo remodeling. This leads to substantial facial disfigurement while in its most severe forms, TAO can threaten eye sight. In this brief paper, I review some of the background investigation that has led to development of teprotumumab as the first and only US FDA approved medical therapy for TAO. This novel treatment was predicated on recognition that the insulin-like growth factor I receptor plays an important role in the pathogenesis of TAO. It is possible that a similar involvement of that receptor in other autoimmune disease may lead to additional indications for this and alternative insulin-like growth factor I receptor-inhibiting strategies.

Highlights

Thyroid-associated ophthalmopathy (TAO), known as thyroid eye disease or Graves’ orbitopathy, remains a vexing disease process most frequently occurring in individuals with Graves’ disease (GD) [1]
On the strength of two successful clinical trials involving patients with active, moderate to severe disease, teprotumumab has recently been approved by the Food and Drug Administration (FDA) for use in TAO [9]
With regard to the secondary outcomes, those patients receiving teprotumumab responded with a change in proptosis from baseline and clinical activity score (CAS) from baseline when compared to those receiving placebo

Summary

INTRODUCTION

Thyroid-associated ophthalmopathy (TAO), known as thyroid eye disease or Graves’ orbitopathy, remains a vexing disease process most frequently occurring in individuals with Graves’ disease (GD) [1]. TAO can present with a variety of physical signs and symptoms, many of which are shared with other more common diseases of the tissues surrounding the eye In this brief review, I attempt to provide the historical background underpinning efforts to identify an effective and safe medical therapy for TAO. On the strength of two successful clinical trials involving patients with active, moderate to severe disease, teprotumumab has recently been approved by the FDA for use in TAO [9]. This approval has ushered in to clinical practice a new era for medically managing this serious and historically underserved manifestation of thyroid autoimmunity

CURRENT UNDERSTANDING OF TAO PATHOGENESIS

Findings

WHAT MIGHT LAY AHEAD FOR TEPROTUMUMAB IN TAO AND BEYOND