Smokers, women experience proptosis reduction with teprotumumab in thyroid eye disease
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High-risk adults with active thyroid eye disease, such as smokers, women and older adults, experienced a reduction in outward bulging of the eye at 24 weeks that was similar to adults at lower risk for the disease, according to findings accepted for presentation at the Endocrine Society Annual Meeting.
“We conducted this analysis to provide further evidence for physicians to consider when determining the type of patient to treat with Tepezza,” George J. Kahaly, MD, PhD, professor of medicine, endocrinology and metabolism at Johannes Gutenberg University Medical Center in Mainz, Germany, told Healio. “We were particularly interested in understanding whether patients who fall in higher-risk populations — including advanced age, women and smokers — have the same reduction in proptosis as those who are less at risk for developing thyroid eye disease. For instance, smoking is a risk factor for thyroid eye disease and can make it more serious and difficult to manage. It’s exciting to see in this analysis that 70% of smokers were proptosis responders, with a mean reduction of almost 3 mm. This is comparable to results seen in nonsmokers.”
Teprotumumab (Tepezza, Horizon Therapeutics), an insulin-like growth factor I receptor inhibitor, is a fully human monoclonal antibody developed to address a substantial unmet need for patients with thyroid eye disease. The drug blocks the inflammatory/autoimmune pathophysiology that underlies thyroid eye disease.
Kahaly and colleagues analyzed data from two 24-week randomized, double-blind, placebo-controlled, parallel-group studies enrolling 171 adults with active thyroid eye disease associated with Graves’ disease. Researchers randomly assigned participants to infusions of teprotumumab (n = 84; mean age, 51.5 years; 69% women; 24% smokers) or placebo (n = 87; mean age, 51.4 years; 77% women; 30% smokers) every 3 weeks (eight infusions). The study eye designated at baseline manifested more severe thyroid eye disease and a clinical activity score of at least 4. Researchers stratified participants by sex, smoking status and baseline age (younger or older than 65 years). Researchers examined percentage of proptosis responders ( 2 mm) and proptosis change from baseline.
“In thyroid eye disease, smoking is one of the core contributors that turns thyroid eye disease from a relatively moderate disease into something much more severe,” Raymond Douglas, MD, PhD, director of the Orbital and Thyroid Eye Disease Program at Cedars-Sinai Medical Center, told Healio after a presentation to the press this week. “Smoking has been associated with worse disease outcomes, worse optic neuropathy and worse response to anti-inflammatory treatment. One of the first things we advise patients is to avoid smoking of any type with this disease.”
At week 24, researchers found that more adults in the teprotumumab group were responders vs. placebo in analyses stratified by sex (men, 73.1% vs. 5%; women, 79.3% vs. 17.9%), smoking status (smokers, 70% vs. 23.1%; nonsmokers, 79.7% vs. 11.5%) and age (younger, 76.1% vs. 16.2%; older, 84.6% vs. 7.7%; P < .001 for all).
In continuous variable analyses, the mean proptosis reduction from baseline was also greater at week 24 among adults in the teprotumumab group vs. placebo. Mean proptosis reduction was –3.34 mm vs. –0.07 mm for men, –3.1 mm vs. –0.42 mm for women, –2.99 mm vs. –0.72 mm for smokers, –3.2 mm vs. –0.31 mm for nonsmokers, –3.1 mm vs. –0.39 mm for younger participants and –3.55 mm vs. –0.22 mm for older participants (P < .001 for all).
“The key takeaway is that Tepezza significantly reduces proptosis in patients with thyroid eye disease regardless of age, gender and smoking status,” Kahaly said. “Until the recent FDA approval of Tepezza, patients have not had a medicine that addresses the underlying biology of the disease and has been shown to significantly improve proptosis and diplopia, which patients often say are the most debilitating aspects of the disease. These data are additional important considerations for physicians when making treatment decisions.”
As Healio previously reported, the FDA approved teprotumumab for the treatment of adults with thyroid eye disease in January, making it the first drug approved for the condition. – by Regina Schaffer
Reference:
Kahaly GJ, et al. OR18-01. The Endocrine Society Annual Meeting; 2020 (conference canceled/virtual meeting).
Disclosures: Horizon Therapeutics sponsored the trials. Douglas reports he serves as a consultant for Horizon Therapeutics. Kahaly reports Johannes Gutenberg University Medical Center has received research-associated funding from Horizon and River Vision.