The mechanism of action of teprotumumab in patients with TED has not been fully characterized. Teprotumumab-trbw binds to IGF-1R and blocks its activation and signaling.

IGF-1R, insulin-like growth factor-1 receptor.

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TEPEZZA prevents disease progression by
treating a root cause of Thyroid Eye Disease (TED)1-5

TEPEZZA is designed to target and block IGF-1R, a key driver of TED pathophysiology throughout the course of the disease.1-5 By inhibiting IGF-1R, TEPEZZA prevents muscle and tissue expansion behind the eye to help reduce TED symptoms.2,4,5

Rendering of autoantibodies stimulating orbital fibroblasts by activating the IGF-1R/TSHR signaling complexRendering of autoantibodies stimulating orbital fibroblasts by activating the IGF-1R/TSHR signaling complex

In TED, autoantibodies activate the IGF-1R/TSHR signaling complex, which stimulates orbital fibroblasts.2,6,7

Rendering of activated orbital fibroblasts causing severe inflammation and tissue expansion in muscle and fat cells behind the eyeRendering of activated orbital fibroblasts causing severe inflammation and tissue expansion in muscle and fat cells behind the eye

Once activated, orbital fibroblasts proliferate and cause expansion of fat and muscle tissue behind the eye.3,6

Rendering showing how TEPEZZA works to target and block IGF-1R and inhibit fibroblast activation through the IGF-1R/TSHR signaling complexRendering showing how TEPEZZA works to target and block IGF-1R and inhibit fibroblast activation through the IGF-1R/TSHR signaling complex

TEPEZZA targets and blocks IGF-1R and inhibits fibroblast activation via the IGF-1R/TSHR signaling complex at a root cause of the disease.1,2,4

Rendering showing TEPEZZA's novel MOA targeting IGF-1R in Thyroid Eye Disease to decrease proptosisRendering showing TEPEZZA's novel MOA targeting IGF-1R to decrease proptosis

TEPEZZA targets IGF-1R and decreases proptosis by1,3-6,8

  • Preventing muscle and fat-tissue remodeling
  • Reducing tissue expansion behind the eye

Teprotumumab-trbw’s mechanism of action in patients with Thyroid Eye Disease has not been fully characterized. Teprotumumab-trbw binds to IGF-1R and blocks its activation and signaling.

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Preview of TEPEZZA (teprotumumab-trbw) mechanism of action video
Read transcript

Welcome, doctor.

You are here to learn how to identify and treat a rare and potentially debilitating disease affecting the human eye.

Although sometimes referred to as Graves’ orbitopathy, Thyroid Eye Disease, or T-E-D, is separate and distinct from Graves’ disease and has a unique underlying mechanism.Treating Graves’ may not lead to improvement in the clinical manifestations of T-E-D.

In Graves’ disease, autoantibodies target the thyroid-stimulating hormone receptor, triggering hyperthyroidism.

T-E-D is a potentially vision-threatening, chronic autoimmune disease with a heterogeneous presentation.

The reason for this difference lies deep within the human body.

Prepare to take a closer look.

In T-E-D, IGF-1R, a key mediator in the disease, and TSHR are colocalized and physically linked to form a functional signaling complex.

Central to the pathogenesis, autoantibodies activate the IGF-1R/TSHR signaling complex, which stimulates orbital fibroblasts, which can remain metabolically active throughout the course of the disease.

Once activated, these fibroblasts can cause potentially severe inflammation and expansion of muscle and fat behind the eye, leading to potentially debilitating downstream effects that are typical of T-E-D, such as proptosis, diplopia, and eyelid retraction.

Common inflammatory effects include, eyelid swelling and erythema, conjunctival redness, chemosis, and inflammation of the caruncle and plica.

Fortunately, you have a treatment option available with TEPEZZA, the first and only FDA-approved treatment for T-E-D.

Through its novel, breakthrough mechanism, TEPEZZA targets and blocks IGF-1R and inhibits fibroblast activation via the IGF-1R/TSHR signaling complex.

IGF-1R inhibition on the surface of the orbital fibroblast is thought to attenuate downstream molecular events such as hyaluronan production, adipogenesis, muscle expansion, and inflammatory cytokine production.

By blocking IGF-1R, treatment with TEPEZZA has been proven to improve proptosis, diplopia, and inflammatory effects in T-E-D patients.

Congratulations, doctor, you now have the information to accurately identify T-E-D and understand the role of TEPEZZA in treating Thyroid Eye Disease.

IGF-1R, insulin-like growth factor-1 receptor; TSHR, thyroid-stimulating hormone receptor.

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See the efficacy of TEPEZZA for TED

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See how TEPEZZA demonstrated results in a variety of patients with TED

INDICATION

TEPEZZA is indicated for the treatment of Thyroid Eye Disease regardless of Thyroid Eye Disease activity or duration.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Infusion Reactions: TEPEZZA may cause infusion reactions. Infusion reactions have been reported in approximately 4% of patients treated with TEPEZZA. Reported infusion reactions have usually been mild or moderate in severity. Signs and symptoms may include transient increases in blood pressure, feeling hot, tachycardia, dyspnea, headache, and muscular pain. Infusion reactions may occur during an infusion or within 1.5 hours after an infusion. In patients who experience an infusion reaction, consideration should be given to premedicating with an antihistamine, antipyretic, or corticosteroid and/or administering all subsequent infusions at a slower infusion rate.

Preexisting Inflammatory Bowel Disease: TEPEZZA may cause an exacerbation of preexisting inflammatory bowel disease (IBD). Monitor patients with IBD for flare of disease. If IBD exacerbation is suspected, consider discontinuation of TEPEZZA.

Hyperglycemia: Increased blood glucose or hyperglycemia may occur in patients treated with TEPEZZA. In clinical trials, 10% of patients (two-thirds of whom had preexisting diabetes or impaired glucose tolerance) experienced hyperglycemia. Hyperglycemic events should be controlled with medications for glycemic control, if necessary. Assess patients for elevated blood glucose and symptoms of hyperglycemia prior to infusion and continue to monitor while on treatment with TEPEZZA. Ensure patients with hyperglycemia or preexisting diabetes are under appropriate glycemic control before and while receiving TEPEZZA.

Hearing Impairment Including Hearing Loss: TEPEZZA may cause severe hearing impairment including hearing loss, which in some cases may be permanent. Assess patients’ hearing before, during, and after treatment with TEPEZZA and consider the benefit-risk of treatment with patients.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥5% and greater than placebo) are muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing impairment, dysgeusia, headache, dry skin, weight decreased, nail disorders, and menstrual disorders.

Please see Full Prescribing Information for more information.

INDICATION

TEPEZZA is indicated for the treatment of Thyroid Eye Disease regardless of Thyroid Eye Disease activity or duration.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Infusion Reactions: TEPEZZA may cause infusion reactions. Infusion reactions have been reported in approximately 4% of patients treated with TEPEZZA. Reported infusion reactions have usually been mild or moderate in severity. Signs and symptoms may include transient increases in blood pressure, feeling hot, tachycardia, dyspnea, headache, and muscular pain. Infusion reactions may occur during an infusion or within 1.5 hours after an infusion. In patients who experience an infusion reaction, consideration should be given to premedicating with an antihistamine, antipyretic, or corticosteroid and/or administering all subsequent infusions at a slower infusion rate.

Preexisting Inflammatory Bowel Disease: TEPEZZA may cause an exacerbation of preexisting inflammatory bowel disease (IBD). Monitor patients with IBD for flare of disease. If IBD exacerbation is suspected, consider discontinuation of TEPEZZA.

Hyperglycemia: Increased blood glucose or hyperglycemia may occur in patients treated with TEPEZZA. In clinical trials, 10% of patients (two-thirds of whom had preexisting diabetes or impaired glucose tolerance) experienced hyperglycemia. Hyperglycemic events should be controlled with medications for glycemic control, if necessary. Assess patients for elevated blood glucose and symptoms of hyperglycemia prior to infusion and continue to monitor while on treatment with TEPEZZA. Ensure patients with hyperglycemia or preexisting diabetes are under appropriate glycemic control before and while receiving TEPEZZA.

Hearing Impairment Including Hearing Loss: TEPEZZA may cause severe hearing impairment including hearing loss, which in some cases may be permanent. Assess patients’ hearing before, during, and after treatment with TEPEZZA and consider the benefit-risk of treatment with patients.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥5% and greater than placebo) are muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing impairment, dysgeusia, headache, dry skin, weight decreased, nail disorders, and menstrual disorders.

Please see Full Prescribing Information for more information.

  1. TEPEZZA (teprotumumab-trbw) [prescribing information] Horizon.
  2. Patel A, Yang H, Douglas RS. A new era in the treatment of Thyroid Eye Disease. Am J Ophthalmol. 2019;208:281-288.
  3. Bahn RS. Graves’ ophthalmopathy. N Engl J Med. 2010;362(8):726-738.
  4. Douglas RS. Teprotumumab, an insulin-like growth factor-1 receptor antagonist antibody, in the treatment of active Thyroid Eye Disease: a focus on proptosis. Eye (Lond). 2019;33(2):183-190.
  5. Douglas RS, Kahaly GJ, Patel A, et al. Teprotumumab for the treatment of active Thyroid Eye Disease. N Engl J Med. 2020;382(4):341-352.
  6. Dik WA, Virakul S, van Steensel L. Current perspectives on the role of orbital fibroblasts in the pathogenesis of Graves’ ophthalmopathy. Exp Eye Res. 2016;142:83-91.
  7. Ugradar S, Kang J, Kossler AL, et al. Teprotumumab for the treatment of chronic Thyroid Eye Disease. Eye (Lond). 2022;36(8):1553-1559.
  8. Data on File. Horizon, November 2020.