Teprotumumab Improves Proptosis in Thyroid Eye Disease

Teprotumumab significantly improved proptosis versus placebo in longstanding/low inflammation thyroid eye disease (TED) according to data from the first placebo-controlled trial of the drug that was recently published in The Journal of Clinical Endocrinology & Metabolism. (Horizon Therapeutics funded the trial and is marketing the drug as TEPEZZA.)

Researchers led by Raymond S. Douglas, MD, PhD, of the Department of Ophthalmology at Cedars Sinai Medical Center in Los Angeles, point out that early TED can lead to symptomatic chronic disease, including proptosis, which can be debilitating. Teprotumumab, an insulin-like growth factor-1 receptor (IGF-1R) inhibitor, was the first drug approved for TED treatment, in 2020 in the United States, and has shown promise and has been recommended as the first-line treatment for a wide group of patients with moderate to severe TED presenting with active inflammation and significant proptosis and/or diplopia.

“Although several observational reports have been published indicating favorable effects of teprotumumab in a wide group of patients with chronic TED, there are no well-controlled study data with teprotumumab in patients with longer duration of TED without active inflammation,” the authors write. “We report results of the first randomized, double-masked, placebo-controlled trial in patients with TED with low clinical activity. The objective of this study was to investigate the efficacy, safety, and tolerability of teprotumumab in patients with long-duration TED and low disease activity as assessed by the [Clinical Activity Score (CAS)].”

For this study, the researchers randomized 62 adult participants who have had TED for two to 10 years. Forty-two patients received intravenous teprotumumab while 20 received placebo once every three weeks, for a total of eight infusions. At week 24, proptosis improvement was greater with teprotumumab than with placebo. “Patients in this trial had a statistically significant decrease, as assessed by [least squares] mean changes in mm of proptosis and a higher percentage of patients with a 2 mm reduction from baseline (62%) as compared with placebo,” the authors write. (Adverse effects like hyperglycemia and hearing impairment were also noted, as in previous teprotumumab trials.)

“The results from this randomized controlled study add to the increasing body of literature from real-world clinical practice on teprotumumab’s efficacy in treating TED,” the authors conclude. “These data demonstrate that teprotumumab significantly reduced proptosis from baseline with a higher rate of proptosis response compared with placebo in patients with longstanding TED and low clinical disease activity.”