BACKGROUND
Graves’ disease is the most common cause of hyperthyroidism in the United States. Graves’ disease can be associated with an eye complication called “Thyroid Eye Disease” (TED). TED is an autoimmune disorder caused by the same antibody that leads to Graves’ hyperthyroidism. This condition is characterized by growth of fat, muscle and other tissues behind the eyes and can manifest as bulging (proptosis) of the eyes, tearing, redness, lid swelling, double vision and in severe cases -loss of vision. While TED can occur in up to half of the patients with Graves’ disease, most of the time it is mild. For those patients with severe TED, steroids and/or radiation have been the standard medical treatment. However, the success of such treatments has been limited and short-lasting.

A new drug called Teprotumumab (Tepezza®) was recently developed to treat TED. This medication is an antibody that blocks a receptor (the insulin-like growth factor 1 receptor) located on fibroblast cells. By blocking this receptor, the growth of tissues behind the eyes is blunted. This drug is given as an intravenous infusion every three weeks for a total of eight infusions. The initial studies showed promising results: alleviation of symptoms and improvement of vision for patients with TED. Indeed, the American and European Thyroid Associations now recommend the use of teprotumumab for patients with moderate to severe TED. This study looks at patients with TED who were part of the original trials and examines the effects of the drug over a longer period.

THE FULL ARTICLE TITLE
Kahaly GJ et al. Long-term efficacy of teprotumumab in thyroid eye disease: follow-up outcomes in three clinical trials. Thyroid. Epub 2024 Jun 2; doi: 10.1089/ thy.2023.0656. PMID: 38824618.

SUMMARY OF THE STUDY
This study looks at 121 patients with TED who were part of the original three clinical trials performed in the US and Europe.

The patients were treated with either teprotumumab or placebo and followed over an extended period. The authors assessed the severity of the TED by using clinical scales called clinical activity scores (CAS). A decrease of 2 or more in CAS points was considered a good result. Authors also looked at the necessity for more treatments, such as steroids and surgery or repeat teprotumumab infusions due to either lack of effect or loss of initial response to the treatment. The authors also looked at the quality of life of the patients by administering a questionnaire.

CAS response to teprotumumab was high: 87% at week 24, 79% at week 48, 84% at week 60, and 91% at week 72. Quality of life, visual appearance and functional vision (ability to perform daily activities) were improved and stable over time. Of the patients who responded initially, 70-90% maintained the response at 72 weeks. Overall, 20% of the patients needed additional treatments for their TED, including eye surgery. There were some side effects on a few patients including high sugars and loss of hearing.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study shows: 1) that teprotumumab is very effective at treating TED, particularly in patients with proptosis and double vision, and 2) that the improvements are long lasting. Although, these studies did not directly compare the effects of the drug with that of steroids, it is fair to conclude based on previous data, that teprotumumab is superior to steroids. It is important to note that other smaller studies looking at this drug showed lower response rates. Longer follow up data is needed to better evaluate the overall effect of this drug in a wider variety of patients with TED.

— Susana Ebner MD

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