A New Era in the Treatment of Thyroid Eye Disease

Improved understanding of thyroid eye disease (TED) pathogenesis has facilitated identification of a targeted molecular approach for TED treatment offering the potential to halt or slow disease progression in a nonsurgical manner. Herein, we provide a summary of the current knowledge of TED manageme...

Full description

Saved in:
Bibliographic Details
Published in:American journal of ophthalmology 2019-12, Vol.208, p.281-288
Main Authors: Patel, Amy, Yang, Huasheng, Douglas, Raymond S.
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal, Humanized - therapeutic use
Autoimmune diseases
Binding sites
Cytokines
Deformities
Drug therapy
Edema
Exophthalmos - physiopathology
Extracellular matrix
Eye diseases
Fibroblasts
Financial disclosure
Graves Ophthalmopathy - drug therapy
Graves Ophthalmopathy - metabolism
Humans
Immunoglobulins
Inflammation
Insulin-like growth factors
Kinases
Lymphocytes
Ophthalmology
Pathogenesis
Patients
Quality of life
Randomized Controlled Trials as Topic
Receptor, IGF Type 1 - antagonists & inhibitors
Receptor, IGF Type 1 - metabolism
Thyroid gland
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Improved understanding of thyroid eye disease (TED) pathogenesis has facilitated identification of a targeted molecular approach for TED treatment offering the potential to halt or slow disease progression in a nonsurgical manner. Herein, we provide a summary of the current knowledge of TED management, followed by discussion of a novel insulin-like growth factor-1 receptor (IGF-1R) antagonist antibody and its potential to change the course of the disease. Perspective. Review of the literature and authors' experience. Many publications demonstrate IGF-1R overexpression in TED, and its activation as an autoantigen as a critical factor in TED pathogenesis. Several in vitro studies demonstrate that IGF-1R inhibition attenuates downstream molecular events including cytokine and hyaluronan production, and cellular differentiation. These observations led to the hypothesis that blocking IGF-1R may abrogate the clinical progression of TED. The recent completion of phase 2 and 3 randomized, placebo-controlled trials demonstrate the efficacy and safety of teprotumumab, a fully human monoclonal IGF-1R antagonist antibody, in patients with moderate-to-severe, active TED. Both the phase 2 and the recent phase 3 study results demonstrate that more patients with active TED receiving teprotumumab experienced a meaningful improvement in proptosis. Current TED treatment strategies target inflammation and symptoms, but do not modify the disease course. Therefore, proptosis as well as strabismus and its resulting diplopia often remain, impacting patient well-being and quality of life over the long term. Targeted molecular therapy using teprotumumab demonstrates disease-modifying benefits with the potential to shift the paradigm for TED treatment.
ISSN:0002-9394
1879-1891
DOI:10.1016/j.ajo.2019.07.021