Teprotumumab: How Effective Is the First Drug Approved for Thyroid Eye Disease?

Swollen, red eye

[This post was originally published on the Harvard Medical School Trends in Medicine blog and has been republished here with permission.]

By Rohit Jain, B. Pharmacy, MBA, PGDBM, LL.B, DCR
November 24, 2020

Thyroid eye disease (TED) is also termed as ophthalmopathy or Grave’s orbitopathy. TED is an autoimmune condition whereby the lacrimal glands, eyelids, and periorbital muscles become inflamed. The condition is present in almost 2% of patients with thyroiditis and 25–50% of patients suffering from Grave’s Disease. Approximately 80–90% of patients with thyroid eye disease have hyperthyroidism while the rest have hypothyroidism or euthyroidism. TED leads to a constellation of symptoms and signs including conjunctival injection, lid retraction, periorbital edema, and the characteristic appearance of exophthalmos. Severe exophthalmos can cause incomplete eyelid closure with corneal exposure, resulting in dryness, and abrasions. In advanced cases of TED, enlargement of periorbital tissues may compress the optic nerve leading to partial or complete vision loss.

Disease Pathophysiology

The exact pathogenesis of thyroid eye disease is not clearly understood. It is believed that autoantibodies to thyroid-stimulating hormone receptor (TSHR) have an important role in thyroid eye disease. However, this theory does not explain the development of diseases in patients who are hypothyroid or with a normal functioning thyroid gland. Additional studies suggest that another receptor, the insulin-like growth factor 1 receptor (IGF-1R), may be responsible for the development of disease in such patients. Anti-IGF-1R antibodies can activate the insulin-like growth factor receptor, which turns on signaling pathways and target gene expression.  This results in the production of hyaluronan and other glycosaminoglycans resulting in fibrosis, swelling and expansion of orbital tissue, with resulting complications. Fat in the orbital area may also increase due to adipogenesis.

Teprotumumab: An introduction

In January 2020, the FDA approved teprotumumab for the treatment of TED. The drug has been granted fast-track status, orphan drug designation, and a breakthrough therapy designation. Teprotumumab is a fully human IgG1 monoclonal antibody that inhibits the IGF1 receptor (IGR1-R), blocking its activation and downstream signaling. It is an intravenous medication, with an initial dose of the drug 10 mg/kg, followed by 20 mg/kg every 3 weeks for 7 additional infusions.

Efficacy of Teprotumumab

The efficacy of teprotumumab was determined through two randomized, double-blinded, placebo-controlled studies. In study 1 (NCT01868997), 42 patients were randomized to teprotumumab and 45 patients were randomized to placebo. Almost 69% of patients receiving teprotumumab showed improvement in proptosis and continued to improve through week 24 as compared to only 20% in the placebo group. In respect to diplopia, the response rate in teprotumumab was higher as compared to placebo group.

Study 2 (NCT03298867) also had 41 patients treated with teprotumumab, versus 42 in the placebo arm. 83% of patients treated with teprotumumab showed an improvement in proptosis. Secondary outcomes assessed included overall response, mean change in proptosis, clinical activity score of 0 or 1, diplopia response, and mean change in GO-QOL overall score. All secondary outcomes were significantly better in the teprotumumab group as compared to placebo.

In study 2, the drug was generally well tolerated with a similar side effect profile to placebo. Two patients had an infusion reaction due to teprotumumab; which led to one patient discontinuing the drug. Hearing impairment was reported in five patients in the treatment group, but none in the placebo group; there also were patients with weight loss in the treatment vs placebo arm.


These early studies demonstrated that treatment with teprotumumab was effective for management of TED and led to improvements in proptosis, diplopia, clinical activity score, and overall quality of life as compared to placebo. With the approval of teprotumumab, doctors now have at least one drug to manage TED, and this may be a viable alternative to surgical management.


Rohit Jain

Rohit Jain is a medical writing expert, medico-marketing trainer, and patent specialist who has written various medical articles covering different therapeutic areas. He is a registered patent agent in India and is currently pursuing a Masters in Pharmacy. He has more than a decade of experience in the pharmaceutical industry and as an avid reader, his interests include reading about the latest research in the medical and pharmaceutical arenas.

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