Teprotumumab for thyroid eye disease

Teprotumumab for thyroid eye disease

the FDA approved teprotumumab (Tepezza) in 2020 for the treatment of adults with thyroid eye disease (TED). The drug is an insulin-like growth factor 1 receptor (IGF-1R) inhibitor, a fully humanized monoclonal antibody produced in Chinese hamster ovary cells (CHO-DG44), with a molecular weight of ~148 kilodaltons.1

Through scientific advances and important studies by many researchers around the world, there has been a better understanding of the pathophysiology of TED and autoimmune diseases. Biological therapies have changed the approach in the treatment of TED,3 making teprotumumab a novel and unique therapeutic approach in the treatment of TED.

Currently, it is the only FDA-approved medication available for TED and its symptoms. It shows promise compared to traditional approaches of giving supplements or vitamins, steroids, and surgery. These therapies stop the inflammation, but they are often not sustainable.3

Biologics, such as teprotumumab, have a better safety and efficacy profile because they have the advantage of targeted therapeutic options, leading to precise immune modulation. Therefore, this represents a better alternative treatment option for a niche group of people with SDD.

TED is a complex disease associated with a progressive autoimmune disease that occurs when the body’s immune system attacks the tissue behind the eyes, causing eye inflammation. The swollen tissues push forward and cause the eyes to bulge (proptosis).

This prevents the eyelids from closing completely, showing symptoms such as dry eyes, gritty eyes, watery eyes, blurred vision, eye pain, and double vision (diplopia). It is not only a visual impairment, but also a facial disfigurement, which has a negative and appreciable impact on the patient’s quality of life.

When TED is left untreated, it can increase the risk of irreversible nerve damage and vision loss. Therefore, it is critical to treat TED as soon as possible to prevent further eye damage and long-term negative effects on disease outcomes.4


Teprotumumab has been found to be safe and highly effective in reducing proptosis, diplopia, and improving quality of life after 24 weeks of treatment.

Mechanism of action

The mechanism of action of teprotumumab in patients with TED has not been fully characterized. IGF-1Rs are cellular receptors found on the surface of the tissue at the back of the eyes.

These receptors act like switches; in normal eyes, these switches are “off.” However, in TED patients, the switches are activated by the body’s own immune cells, and turning “on” causes local tissue swelling and inflammation, leading to proptosis, pain, and diplopia of the eyes.

In teprotumumab treatment, monoclonal antibody presentation binds to IGF-1R and blocks its activation and downstream signaling pathway.1 Therefore, it reduces inflammation, which translates into a reduction in signs and symptoms such as proptosis, pain and diplopia.

Dosage and administration

Teprotumumab is administered by systemic intravenous (IV) infusion, available as a 500-mg lyophilized powder in a single-dose vial for reconstitution for injection. The initial dose is an IV infusion of 10 mg/kg over 60 to 90 minutes followed by 20 mg/kg every 3 weeks for 7 additional infusions.1

Clinical studies

Teprotumumab, an IGF-1R inhibitor monoclonal antibody, has been studied in multicenter, double-blind, placebo-controlled clinical trials and has been shown to reduce eye bulging, improve double vision, relieve eye pain, redness, swelling, improve visual capacity, appearance and a better quality of life.two

Contraindications and warnings

Teprotumumab can cause infusion reactions; based on clinical studies, infusion reactions have been reported in approximately 4% of patients. Infusion reactions can occur during treatment or within 24 hours after treatment ends.

Signs and symptoms of the infusion are high blood pressure, fast heartbeat, facial flushing or feeling hot, shortness of breath, headache, and muscle pain.1

Precautions have been identified in patients with pre-existing inflammatory bowel disease (IBD) and diabetes. Teprotumumab can cause an exacerbation of pre-existing IBD. In clinical trials, 10% of patients with preexisting diabetes experienced hyperglycemia.1

Use in special population

Pregnant or lactating women: No well-controlled studies of teprotumumab have been conducted in pregnant women and there are insufficient data on the safety of teprotumumab use in this population. Exposure to teprotumumab in utero in cynomolgus monkeys resulted in external and skeletal abnormalities. Therefore, teprotumumab should not be used during pregnancy due to the risk of harm to the fetus. It is not known whether teprotumumab passes into breast milk and is therefore not recommended for nursing women.1

Pediatric: The safety and efficacy of teprotumumab in patients less than 18 years of age have not been evaluated.

geriatric: There is no difference in safety and efficacy in patients 65 years of age and older.

Adverse events (AEs)

Infusion reaction, exacerbation of pre-existing IBD, and hyperglycemia are clinically significant adverse events that have been described as warnings and precautions.1

In clinical trials, AEs in patients occurring in 5% or more who were treated with teprotumumab are muscle spasms, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing impairment, dysgeusia, headache, and dry skin.1

Lastly, all biologic therapies have the potential to cause immune reactivity.1

Nonclinical toxicology

Carcinogenicity, mutagenicity, and impairment of fertility have not been evaluated.1

Storage and handling

Store in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton until ready to use. Protect from light. Do not freeze.1

About the Author

Steffanie Ung is a PharmD candidate at Marshall B. Ketchum University School of Pharmacy, expected to graduate in spring 2023. She completed this article while on a pharmacy-focused virtual advanced pharmacy practice rotation specializing in STACK. For more information on STACK, or to inquire about APPE rotations, visit www.managewithstack.com.


  1. TEPEZZA® (package insert). Deerfield, IL: Horizon Therapeutics USA, Inc; 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3e6c54a1-cefd-4a5b-a855-ab9f268b6cce
  2. Horizon Pharma USA, Inc. Treatment of Graves’ orbitopathy (thyroid eye disease) to reduce proptosis with teprotumumab infusions in a randomized, placebo-controlled clinical trial (OPTIC). https://www.clinicaltrials.gov/ct2/show/study/NCT03298867?term=teprotumumab&draw=2&rank=3. Retrieved October 1, 2022
  3. Men CJ, Kossler AL, Wester ST. Updates on understanding and treating thyroid eye disease. Ther Adv Ophthalmol.2021 Jun 30;13:25158414211027760. PMID: 34263138; PMCID: PMC8252358
  4. Taylor PN, Zhang L, Lee RWJ, Muller I, Ezra DG, Dayan CM, Kahaly GJ, Ludgate M. New insights into the pathogenesis and nonsurgical management of Graves’ orbitopathy. Nat Rev Endocrinol. 2020 February; 16(2):104-116. Doi:10.1038/s41574-019-0305-4. Epub 2019 December 30. PMID: 31889140.

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