BACKGROUND
Graves’ disease is an autoimmune condition in which patients produce antibodies (TSI or TRAb) that attack the thyroid, turning it on and causing an overactive thyroid gland. This condition can be associated with inflammation of the eyes and the muscles that move the eyes, known as Thyroid Eye Disease (TED). This inflammation can also lead to enlargement of the muscles that control eye movements and cause eye bulging (proptosis), eye swelling and double vision. Mild TED is common and does not require treatment. However, moderate to severe TED can be devastating. Fortunately, this is seen only in a few patients with Graves’ disease.

Until recently, treatment for TED was limited to radiation therapy to the eye sockets and surgery. The game-changer has been a drug known as Teprotumumab (TempezzaTM) which blocks receptors in the eye muscles that are associated with inflammation. This drug was FDA approved in 2020 for TED treatment. Initial studies demonstrated that Teprotumumab improved the eye symptoms of patients with severe, active TED. It was unknown whether Teprotumumab would be effective in chronic TED patients without evidence of active eye inflammation. This study sought to determine if Teprotumumab would be beneficial to patients with chronic TED without evidence of active ongoing inflammation.

THE FULL ARTICLE TITLE
Douglas RS, Couch S, Wester ST, et al. Efficacy and safety of teprotumumab in patients with thyroid eye disease of long duration and low disease activity. J Clin Endocrinol Metab 2023;109(1):25-35; doi: 10.1210/clinem/dgad637. PMID: 37925673.

SUMMARY OF THE STUDY
The study was conducted at 11 sites in the United States. Patients with stable or inactive TED were enrolled in the study and randomly assigned to receive 8 infusions of teprotumumab or placebo once every 3 weeks. Stable/ inactive disease was defined as a Clinical Activity Score (CAS) ≤ 1 in both eyes prior to screening for at least 1 year.

Patients with prior eye surgery, radiation or treatment with steroids in the prior 3 weeks were ineligible to be in the study. Patients were evaluated at baseline and every 3 weeks with the final assessment at week 24 for eye symptoms and adverse reactions. The main study outcome was to assess the effect of the drug or placebo on proptosis (eye bulging) at week 24. A total of 62 patients (42 teprotumumab group, 20 placebo group) were enrolled in the trial.

At week 24, patients treated with teprotumumab had significantly less proptosis compared to placebo (average reduction of -2.41 mm vs -0.92 mm). More patients with teprotumumab had a response to therapy compared to placebo (61.9% vs. 25%). A total of 6 patients treated with Teprotumumab also had eye MRI imaging at baseline and 24 weeks. MRI imaging demonstrated a reduction in eye muscle volume with Teprotumumab. Teprotumumab patients also experienced greater improvements in eye disease related quality of life compared to controls. There were no differences in improvement in double vision between groups. There were no unexpected adverse effects for teprotumumab treated patients compared to prior studies. Teprotumumab treated patients experienced significantly more muscle spasms, headaches, high blood pressure, elevated glucose and hearing impairments compared to placebo treated patients.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
Thyroid eye disease (TED) can cause chronic eye symptoms for patients with Graves’ disease, including patients with chronic mild and less active eye disease. This study demonstrated that teprotumumab treatment significantly improved proptosis in patients with long standing TED with low or no evidence of active inflammation. This suggests that medical therapy with Teprotumumab can be considered in patients with stable, less active but symptomatic chronic thyroid eye symptoms after full discussion of the potential risks and benefits.

— Whitney Woodmansee MD

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