Teprotumumab for the treatment of thyroid eye disease

ABSTRACT

Introduction

Thyroid eye disease (TED) is an autoimmune disease characterized by inflammation of orbital and extraocular muscles. It induces proptosis and diplopia, leading to a worsening of quality of life (QoL) because of its impact on physical appearance, and visual function. The natural history involves an ‘active TED,’ which is an autoimmune inflammatory response targeting orbital soft tissues, and ‘inactive TED,’ where there is tissue expansion remodeling. To date, glucocorticoids represent the main medical therapy, even if often ineffective and associated with side effects.

Areas covered

In TED, the autoimmune process leads to production of TSH-R and IGF-1 R autoantibodies. This induces inflammatory changes in the orbital tissue, and activation of fibroblasts with accumulation of glycosaminoglycans, leading to consequent proptosis, and diplopia. In two previous randomized, double-masked, placebo-controlled, parallel-group, multicenter trials, teprotumumab has been shown to be effective in improving proptosis, inflammation, diplopia, and QoL. More recently, it has been shown that teprotumumab is also effective in chronic-inactive TED. Teprotumumab was approved by the FDA on 21 January 2020 for the treatment of TED.

Expert opinion

For the above-mentioned reasons teprotumumab represents a potential first line therapy for TED that could replace the use of steroids in the next future.

KEYWORDS:

• Graves’ ophthalmopathy therapy
• graves’ disease
• IGF-1 R
• IGF-1 R autoantibodies
• teprotumumab
• thyroid eye disease

Article highlights

• In TED the autoimmune process leads to the production of TSH-R and IGF-1 R autoantibodies, that induce inflammatory changes in the orbital tissue.

• Teprotumumab is a fully human immunoglobulin G1 monoclonal inhibiting antibody directed against IGF-1 R that reduces the proinflammatory cytokines production, the hyaluronan secretion, and the OF activation in TED.

• Previous teprotumumab clinical trials for TED (2 independent, randomized, double-masked, placebo-controlled, parallel-group, multicenter trials) showed clinically relevant improvement of TED (proptosis, inflammation, diplopia and QoL).

• Teprotumumab was approved by the US FDA on 21 January 2020 for the treatment of TED under the name TEPEZZA (teprotumumab-trbw).

• TED patients of longer disease duration responded similarly to those treated earlier in the disease course; and those with an insufficient initial response or flare may benefit from additional teprotumumab therapy. More recently, it has been shown that teprotumumab is also effective in chronic-inactive TED.

• Consequently, a phase 4 clinical trial (NCT04583735) is actually in recruiting phase, to investigate safety and efficacy of teprotumumab in the management of patients with chronic-inactive TED.

• For the above-mentioned reasons, teprotumumab represents a potential first line therapy for TED that could replace the use of steroids in the next future.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are a consultant, advisor, researcher and lecturer for Horizon Therapeutics and have received research support from Viridian Pharmaceuticals. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Company review

Horizon Therapeutics provided a scientific accuracy review at the request of the journal editor.

Additional information

Funding

This paper was not funded.