Clinical Overview: Teprotumumab for Thyroid Eye Disease

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Teprotumumab is the first fully human IgG1 monoclonal antibody approved by the FDA for the treatment of thyroid eye disease at its source not just reducing the symptoms.

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 inhibitor (IGF-1R), fully humanized monoclonal antibody produced in Chinese hamster ovary (CHO-DG44) cells, with a molecular weight of ~148 kilodaltons.1

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

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

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

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

This prevents the eyelids from completely closing, exhibiting symptoms such as dry eyes, gritty eyes, watery eyes, blurry vision, eye pain, and double vision (diplopia). Not only is it visually impairing, but also facially disfiguring, which has a negative and appreciable impact on the quality of life for the patient.

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

Indications

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

Mechanism of action

Teprotumumab’s mechanism of action in patients with TED has not been fully characterized. IGF-1R are cell receptors found on the surface of the tissue on the back of the eyes.

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

In the treatment of teprotumumab, the presentation of the monoclonal antibodies binds to IGF-1R and blocks its activation and downstream signaling pathway.1 Therefore, it reduces inflammation, which results in the reduction of signs and symptoms such as proptosis, pains, and diplopia.

Dosing and administration

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

Clinical studies

Teprotumumab, a monoclonal antibody inhibitor of IGF-1R has been studied in multicenter, double-masked, placebo-controlled clinical trials demonstrated to reduce eye bulging, improve double vision, provide relief from eye pains, redness, swelling, improve visual ability, physical appearance, and better quality of life.2

Contraindications and warnings

Teprotumumab may cause infusion reactions, according to the clinical studies, infusion reactions have been reported in approximately 4% of patients. Infusion reactions can happen during the treatment, or within 24 hours after the treatment is completed.

Signs and symptoms of infusion are high blood pressure, fast heartbeat, redness of the face or feeling hot, difficulty breathing, headache, and muscle pain.1

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

Use in special population

Pregnant or Lactating women: Well-controlled studies of teprotumumab in pregnant women have not been conducted and there are insufficient data for the safety of the use of teprotumumab in this population. In-utero teprotumumab exposure of cynomolgus monkeys resulted in external and skeletal abnormalities. Therefore, teprotumumab should not be used in pregnancy due to the risk of harming the unborn baby. It is not known if teprotumumab passes into breast milk, therefore not recommended for lactating woman.1

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

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 AEs that has been described warning and precautions.1

In the clinical trials, the AEs of 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 therapeutics have the potential to cause immune reactivity.1

Nonclinical toxicology

Carcinogenesis, mutagenesis, and impairment of fertility have not been evaluated.1

Storage and handling

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

About the Author

Steffanie Ung is a PharmD candidate at Marshall B. Ketchum University College of Pharmacy, anticipated to graduate in spring 2023. She completed this article while on a specialty pharmacy-focused virtual Advanced Pharmacy Practice Rotation at STACK. For more information about STACK, or to inquire about APPE rotations, visit www.managewithstack.com.

References

  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 Study (OPTIC). https://www.clinicaltrials.gov/ct2/show/study/NCT03298867?term=teprotumumab&draw=2&rank=3. Accessed October 1, 2022
  3. Men CJ, Kossler AL, Wester ST. Updates on the understanding and management of 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 Feb; 16(2):104-116. Doi:10.1038/s41574-019-0305-4. Epub 2019 Dec 30. PMID: 31889140.