A New Era in the Treatment of Thyroid Eye Disease - oneGRAVESvoice
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A New Era in the Treatment of Thyroid Eye Disease

key information

source: American Journal of Ophthalmology

year: 2019

authors: Amy Patel, Huasheng Yang, Raymond S. Douglas

summary/abstract:

Purpose:
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.

Design:
Perspective.

Methods:
Review of the literature and authors’ experience.

Results:
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 the 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.

Conclusions:
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.

organization: Cedars Sinai Medical Center, Los Angeles, CA; Sun Yat-sen University, Guangzhou, China

DOI: 10.1016/j.ajo.2019.07.021

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