An overactive thyroid can lead to serious secondary consequences. Individuals with hyperthyroidism and Graves’ disease can experience a multitude of ophthalmic conditions, including, bulging eyes, redness, and irritation. Some patients develop more devastating eye conditions that could even result in blindness. Research published January 2020 in the New England Journal of Medicine, however, sparks new hope for those who now may soon have access to a new drug, teprotumumab (Tepezza), which has been given a fast track to market as an orphan drug to treat the rare disease.  

According to the American Thyroid Association, the ophthalmic complication from Graves’ disease is called Graves’ ophthalmopathy or thyroid eye disease, which results from thyroid overactivity caused by Graves’ disease.

Lead author Raymond S. Douglas, MD, PhD, professor of surgery in the division of ophthalmology at Cedars-Sinai Medical Center in Los Angeles, and his team conducted a phase III multicenter, randomized, double-masked, placebo-controlled trial with 83 patients who had active thyroid disease. Patients were assigned to receive either IV infusions of the IGF-IR inhibitor teprotumumab (41 patients) or a placebo (42 patients) every 3 weeks for 21 weeks. Improvement was measured with the primary outcome of a decrease in the abnormal protrusion (a reduction in proptosis of ≥2 mm considered proptosis response) at Week 24 and clinical activity scores that translated into reduced or absent inflammation. Subjects were also given a Graves’ ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire to complete at clinical trial visits with a pre-established mean change of 6 points or greater considered clinically meaningful.

The investigators reported that the teprotumumab group had a proptosis response rate higher than the placebo group (83% [34 patients] vs. 10% [4 patients], P <.001), as well as significantly improved secondary outcomes, including overall response (78% of patients [32] vs. 7% [3]). The team also reported mean change in GO-QOL overall score (13.79 points vs. 4.43 points) (P ≤.001 for all). 

According to Dr. Douglas, who commented that this new discovery “may be a drug that offers a new approach and a paradigm shift.” Dr. Douglas added, “Teprotumumab was extraordinarily effective. We hope that people with thyroid eye disease won't have to suffer as they have in the past. With treatment, they’re not going to be blind. They’re not going to be disfigured. They can even watch their kids playing soccer when it’s windy.” 

The investigators wrote that most adverse events were mild or moderate in severity, with only two serious events, including one infusion reaction that required treatment discontinuation occurring in the teprotumumab group.

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