BACKGROUND
Thyroid eye disease (TED) is a complex disease that causes inflammation of the eyes, eye muscles and the surrounding tissues. TED is most often seen in patients with Graves’ disease but also can be seen with Hashimoto’s thyroiditis. TED can negatively affect patients’ quality of life, as it can be disfiguring, and, more rarely, threaten vision. TED has two distinct phases: an acute inflammatory phase where pain, eye bulging, double vision and vision loss predominate, followed by a chronic phase, characterized by fibrosis and potential permanent eye bulging and vision changes. The best time to treat TED and prevent long term complications is during the acute inflammatory phase. However until recently, treatment options for TED have been limited.

Recently, our understanding of the causes of TED have focused on inflammation affecting cells known as fibroblasts in the eye muscles. Targeted therapies are emerging, including teprotumumab, a monoclonal antibody that blocks inflammation of the eye fibroclasts. This study reviewed the results of 2 clinical trials of teprotumumab, representing one of the largest controlled study populations of patients with TED to date.

THE FULL ARTICLE TITLE
Kahaly GJ et al Teprotumumab for patients with active thyroid eye disease: a pooled data analysis, subgroup analyses, and off-treatment follow-up results from two randomized, double-masked, placebo-controlled, multicentre trials. Lancet Diabetes Endocrinol. 2021 Jun;9(6):360-372.

SUMMARY OF THE STUDY
This is an analysis of 2 multicenter trials performed at 28 specialized centers (thyroid eye and/or orbital clinics) in Europe and America. The scoring system used to evaluate patients with TED is the Clinical Activity Score (CAS) and is based on classical signs of inflammation (pain, redness, swelling and function) and that helps predict which patients will benefit from immunosuppressive treatment.

Participants were adults with Graves’ disease and recent onset (≤9 months) active moderate-to-severe TED, defined as having a CAS ≥4, who were randomized to receive eight infusions of intravenous teprotumumab or no drug every 3 weeks. Patients who received previous medical or surgical treatment for TED were excluded. Patients were evaluated for the difference from baseline to week 24 in the proportion of patients with a decrease in eye bulging measurements as well as reduction in CAS, improvement in symptoms and overall Graves’ Ophthalmopathy Quality of Life (GO-QOL) Questionnaire results. Additionally, teprotumumab responders were examined at 7 and 51 weeks following the final infusion to assess for acute disease recurrence and long-term responses.

More patients who received teprotumumab (77%) achieved improvement in eye bulging at week 24, compared with 15% of patients who received no drug. Additionally, those with greater baseline eye bulging achieved the biggest reductions. Patients who received teprotumumab had more improvements in visions (70% vs 31%), and a larger decrease in each CAS component. There did not appear to be any worsening of symptoms after the last dose of teprotumumab. The drug was well tolerated and only 3 patients were unable to complete the trial. No new safety concerns or serious adverse events related to teprotumumab were reported during follow-up.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
These data show that teprotumumab results in significant and clinically meaningful improvement in difficult-totreat TED outcomes, especially eye bulging and vision loss. There was no evidence of acute, rebound TED after treatment discontinuation and responses were maintained to 51 weeks after the final infusion of teprotumumab. This is a major step forward in the treatment of patients with TED.

— Alan P. Farwell, MD

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