Reviewed by Raymond S. Douglas, MD, PhD, and Sara T. Wester, MD, FACS
An investigational novel antigen-specific therapy that blocks insulin-like growth factor-1 receptor (IGF-1R)—teprotumumab (Horizon Therapeutics)—significantly reduced both diplopia by one grade and proptosis in patients with active thyroid eye disease (TED) in a phase III placebo-controlled trial.
These findings confirmed those of the phase III study in which more patients had a significant (p < 0.001) improvement in proptosis, the primary study endpoint, compared with placebo, i.e., 82.9% of treated patients compared with 9.5% of placebo patients) (Smith et al. New Engl J Med 2017;376:1748-1761).
TED is a debilitating, progressive ocular disease with many facets, according to Raymond Douglas, MD, PhD, a principal investigator of the Treatment of Graves’ Orbitopathy (Thyroid Eye Disease) to reduce proptosis with teprotumumab infusions in a randomly selected, placebo-controlled, clinical study (OPTIC) Study.
The disease causes an array of visual impairments, with diplopia developing in about 50% of patients, a complication that severely affects patient quality of life and the clinical activity score (CAS), which assesses the activity of TED.
Strabismus and blindness are other potential complications, said Dr. Douglas, professor of surgery, Division of Ophthalmology, and director, Orbital and Thyroid Eye Disease Center, Cedars Sinai Medical Center, Los Angeles. Given the severity of the disease, the need for a treatment is clear—specifically, a treatment that provides molecular targeting of the antigen, he explained.
Sara Tullis Wester, MD, FACS, noted that TED has become an area of interest for her because of the impact the disease has on patients’ lives physically, psychologically, and emotionally.
“It is exciting for me to see that we might have a treatment that could be disease-altering, considering the impact that the disease has on them,” said Dr. Wester, subinvestigator in the OPTIC study, and associate professor of clinical ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami.
TED has an initial active phase followed by a stable phase.
“The ideal treatment would alter that course by altering the disease in the active phase leading to less long-term sequelae,” Dr. Wester said.
Medical treatments used for TED, none of which is FDA approved, include steroids, radiation, tocilizumab, rituximab, and others, and are less than ideal, Dr. Wester noted.