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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ABOUT TED

TED can have a debilitating impact on daily activities1-4

AUTOIMMUNE DISORDER

Thyroid Eye Disease and IGF-1R icon

IGF-1R drives pathophysiology throughout the disease course1-3,5

LIFELONG & PROGRESSIVE

Thyroid Eye Disease progression iconThyroid Eye Disease progression icon

Can potentially threaten vision and reactivate or flare over time1-3,6,7

HIGHLY VARIABLE

TED symptoms variability icon

Signs and symptoms differ from patient to patient3,8

Diagnose early and treat TED proactively

Early intervention can help improve patient outcomes
and avoid potentially permanent damage2,9

Evaluate patients for visible signs and symptoms9

Proptosis illustrationProptosis illustration

PROPTOSIS

Redness, swelling, and tearing illustrationRedness, swelling, and tearing illustration

REDNESS, SWELLING,
& TEARING

Eyelid retraction illustrationEyelid retraction illustration

EYELID
RETRACTION

Ask patients about non-visible signs and symptoms1,9,10

Dry eyes and grittiness illustrationdry eyes gettiness

DRY EYES &
GRITTINESS

Pressure and/or pain behind the eye illustrationpressure pain behind eyes

PRESSURE/PAIN
BEHIND EYES

Diplopia illustrationdiplopia

DIPLOPIA

Color-vision loss illustrationcolor vision loss

COLOR-VISION
LOSS

Not all signs of TED may be visible, so it’s important to ask your patients if they’re experiencing new or changing symptoms. If they are, consider a TED treatment that works at a root cause of the disease.3,9,11

Risk factors can include: smoking (past or present), radioactive iodine treatment, advanced age, female sex, poorly controlled hyper-/ hypothyroidism, and family history of TED or autoimmune diseases9,10,12

Different diseases can sometimes be misdiagnosed
due to similar symptoms1,2,13

American Thyroid AssociationAmerican Thyroid Association

ATA, American Thyroid Association; ETA, European Thyroid Association; TSH, thyroid-stimulating hormone.

DRY EYE DISEASE:Affects lacrimal glands and ocular surface causing
insufficient lubrication to aqueous tear-film layer

Warning icon

TED and Graves’ disease have different underlying mechanisms and require different treatments1,2

Hear how Dr Lisa Mihora uses a team approach to treat her
patients with
Thyroid Eye Disease, and learn about the importance of early diagnosis15,16

Preview of Lisa Dianne Mihora, MD video
Read transcript

Hi. My name is Dr. Lisa Mihora. And I am an oculoplastics surgeon in Phoenix, Arizona. Distinguishing Thyroid Eye Disease and Graves’ disease is important. They’re often linked, but they are two different entities. And Thyroid Eye Disease can actually present before, during, or after the diagnosis of Graves’ disease.

Thyroid Eye Disease can present in patients who are euthyroid, hyperthyroid, or even hypothyroid. And because Thyroid Eye Disease is a separate and distinct disease from Graves’, treating Graves’ does not address the pathophysiology or symptomatology of Thyroid Eye Disease.

In Graves’ disease auto-antibodies target the thyrotropin receptor, which thereby triggers hyperthyroidism. Whereas in Thyroid Eye Disease, we have additional auto antigens and antibodies that are involved.

The understanding of the mechanism of Thyroid Eye Disease has changed, now that insulin-like growth factor-1 receptor, or IGF-1 receptor, has been identified.

We now know that orbital fibroblasts, which are up-regulated in Thyroid Eye Disease, are key drivers of the pathophysiology of Thyroid Eye Disease. The T-cells and fibroblasts activate, and the inflammatory response and cascade has begun.

And the pathophysiology can translate into the signs and symptoms of Thyroid Eye Disease.

Once the fibroblasts are activated, they can cause severe inflammation and over-expansion of tissues, muscle, and the fat cells that are located behind the eye.

Because this is a fixed bony orbit, this can lead to different clinical manifestations.

Inflammation can occur, as well as foreign body sensation. A patient may have excessive tearing or dry eye. There can be conjunctival or eyelid redness, as well as swelling. A patient may have orbital pain, chemosis, proptosis, or bulging eye, and diplopia, or double vision.

Because there are so many different signs and symptoms that a patient can present with, educating patients, as well as our providers, means that we can hone in on the diagnosis earlier, and potentially treat earlier.

The goal of treating Thyroid Eye Disease early, in order to help combat the symptoms a patient may have, is a team approach. A team approach between endocrinology, and ophthalmology, or oculoplastics.

Endocrinology has a very unique role, in that they specialize in treating the autoimmune disorder and the endocrine dysfunctions, such as Graves’ disease and refer early to the ophthalmologist or oculoplastic surgeon, in order to monitor the eye symptomatology.

Ophthalmologists or oculoplastic surgeons can often be the first to diagnose Thyroid Eye Disease patients. A baseline eye exam is conducted. And the patient’s Thyroid Eye Disease is evaluated.

I do co-manage patients with endocrinologists. And I find it very helpful when the endocrinologist now refers a patient early. That way, we can potentially start treatment, and start exams, and start the discussion, as early as possible.

I think that this dual approach to a patient gives a patient the best information and the best team approach, so that both aspects of the Thyroid Eye Disease can be effectively treated and managed.

BURDEN OF TED

TED is a debilitating and potentially disfiguring disease1-3

Vision may also be threatened17,18

Proptosis iconProptosis icon

62% of patients

experienced Proptosis19*

Diplopia iconDiplopia icon

51% of patients

experienced Diplopia20†

Dysthyroid Optic Neuropathy iconDysthyroid Optic Neuropathy icon

6% to 9% of patients

experienced Dysthyroid
Optic Neuropathy18,21,22‡

TED may impact daily activities and emotional well-being4,23

Patient appearance iconPatient appearance icon

66% of patients

suffered a high impact on daily life4§

Anxiety and depression icon Anxiety and depression icon

42% of patients

experienced anxiety and/or depression23ll

Emotional side of Thyroid Eye Disease iconEmotional side of Thyroid Eye Disease icon

36% of patients

reported mental health issues4§

*Based on an incidence cohort of 120 patients with Graves’ orbitopathy in Olmsted County, Minnesota, who were diagnosed between 1976 and 1990.19,21

†Based on a cross-sectional follow-up study carried out from 1998 to 2000 of 168 patients with Graves’ orbitopathy who had started radiotherapy and/or prednisone treatment between 1982 and 1992.20

‡Based on a retrospective study of 1463 cases seen at the University of British Columbia Orbital Clinic between September 1976 and March 1986.22

§Based on retrospective chart review of 714 US patients by assessing physician-perceived impact of moderate-to-severe TED on patients’ quality of life (QOL). High overall QOL impact–score ≥4/7, where 1 meant “not at all impaired” and 7 meant “extremely impaired.4

‖Based on an online QOL assessment survey of 100 patients including all levels of TED severity.23

warning icon

Ask your patients about how the burden of TED effects them, including signs and symptoms, emotional well-being, and daily activity performance

DIAGNOSING TED

Diagnosing Thyroid Eye Disease (TED)

There are a number of diagnostic protocols and tools available to aid in a TED diagnosis. Radiographic imaging with CT or MRI can be helpful. Grading systems include the EUGOGO, VISA, and GO-QOL scales. The Clinical Activity Score (CAS) may be used to identify the signs and symptoms of inflammation characteristic of TED8,9,18
CAS

CAS measurements may be required
for treatment approval

  • The score at each efficacy assessment is the number of all items present24

Clinical Activity Score

  • CAS is a 7-point composite score measuring spontaneous orbital pain, gaze-evoked orbital pain, eyelid swelling, eyelid erythema, conjunctival redness, chemosis, and inflammation of caruncle or plica. A lower score indicates fewer symptoms but does not take symptom severity into account. The CAS is a composite score with equal weighting of a number of factors. However, the factors may not be of equal clinical weight to patients or to physicians treating these patients24,25

Ask your patients if they are currently experiencing or have
ever experienced the following:
  • Spontaneous orbital pain
  • Gaze-evoked orbital pain
  • Eyelid swelling
  • Eyelid erythema
  • Conjunctival redness
  • Chemosis
  • Inflammation of caruncle or plica

Symptoms may not always be noticeable during a baseline examination; at follow-up visits it is important to ask your patients if they are experiencing any new or changing symptoms.3,9,11

A multidisciplinary team is optimal to reduce the
burden of TED4,9,11,26,27

  • TED is best evaluated and co-managed by an endocrinologist, eye care provider, and TED Specialist. A TED Specialist can be an eye specialist provider or an endocrinologist, but this varies depending on each ecosystem and/or neighboring specialties9,28

CT, computerized tomography; EUGOGO, European Group on Graves’ Orbitopathy; GO-QOL, Graves’ ophthalmopathy quality of life; MRI, magnetic resonance imaging; VISA, vision, inflammation, strabismus, and appearance.

TEPEZZA mechanism of action iconTEPEZZA mechanism of action icon

See how TEPEZZA works to treat TED

Find a Thyroid Eye Disease specialist iconFind a Thyroid Eye Disease specialist icon

Find a TED Specialist

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. Bahn RS. Graves’ ophthalmopathy. N Engl J Med. 2010;362(8):726-738.
  2. Wang Y, Patel A, Douglas RS. Thyroid Eye Disease: how a novel therapy may change the treatment paradigm. Ther Clin Risk Manag. 2019;15:1305-1318.
  3. Patel A, Yang H, Douglas RS. A new era in the treatment of Thyroid Eye Disease. Am J Ophthalmol. 2019;208:281-288.
  4. Wang Y, Sharma A, Padnick-Silver L, et al. Physician-perceived impact of Thyroid Eye Disease on patient quality of life in the United States. Ophthalmol Ther. 2021;10(1):75-87. 
  5. 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.
  6. Patel P, Khandji J, Kazim M. Recurrent Thyroid Eye Disease. Ophthal Plast Reconstr Surg. 2015;31(6):445-448.
  7. Douglas RS, Kahaly GJ, Ugradar S, et al. Teprotumumab efficacy, safety and durability in longer-duration Thyroid Eye Disease and re-treatment: OPTIC-X study. Ophthalmology. 2022;129(4):438-449.
  8. Bothun ED, Scheurer RA, Harrison AR, Lee MS. Update on Thyroid Eye Disease and management. Clin Ophthalmol. 2009;3:543-551.
  9. Barrio-Barrio J, Sabater AL, Bonet-Farriol E, Velázquez-Villoria Á, Galofré JC. Graves’ ophthalmopathy: VISA versus EUGOGO classification, assessment, and management. J Ophthalmol. 2015;2015:249125.
  10. Thyroid Eye Disease. National Organization for Rare Disorders. 2020. Accessed December 8, 2022. https://rarediseases.org/rare-diseases/thyroid-eye-disease
  11. TEPEZZA (teprotumumab-trbw) [prescribing information] Horizon.
  12.  Risk factors for the development of Thyroid Eye Disease in patients with Graves’ disease. Clin Thyroidology for the Public. 2021;14(8):5-6.
  13. Verjee MA, Brissette AR, Starr CE. Dry eye disease: early recognition with guidance on management and treatment for primary care family physicians. Ophthalmol Ther. 2020;9:877-888.
  14. Burch HB, Perros P, Bednarczuk T, et al. Management of Thyroid Eye Disease: a consensus statement by the American Thyroid Association and the European Thyroid Association. Thyroid. 2022;32(12):1439-1470.
  15. Dolman PJ. Grading severity and activity in Thyroid Eye Disease. Ophthalmic Plast Reconstr Surg. 2018;34(4S supp 1):S34-S40.
  16. Ozzello DJ, Dallalzadeh LO, Liu CY. Teprotumumab for chronic Thyroid Eye Disease. Orbit. 2022;41(5):539-546.
  17. Ponto KA, Merkesdal S, Hommel G, Pitz S, Pfeiffer N, Kahaly GJ. Public health relevance of Graves’ orbitopathy. J Clin Endocrinol Metab. 2013;98(1):145-152.
  18. McAlinden C. An overview of Thyroid Eye Disease. Eye Vis (Lond). 2014;1:9.
  19.  Bartley GB, Fatourechi V, Kadrmas EF, et al. Clinical features of Graves’ ophthalmopathy in an incidence cohort. Am J Ophthalmol. 1996;121(3):284-290.
  20. Terwee C, Wakelkamp I, Tan S, Dekker F, Prummel MF, Wiersinga W. Long-term effects of Graves’ ophthalmopathy on health-related quality of life. Eur J Endocrinol. 2002;146(6):751-757.
  21. Bartley GB. The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota. Trans Am Ophthalmol Soc. 1994;92(1):477-588.
  22. Neigel JM, Rootman J, Belkin RI, et al. Dysthyroid optic neuropathy. The crowded orbital apex syndrome. Ophthalmol. 1988;95(11):1515-1521.
  23. Cockerham KP, Padnick-Silver L, Stuertz N, Francis-Sedlak M, Holt RJ. Quality of life in patients with chronic Thyroid Eye Disease in the United States. Ophthalmol Ther. 2021;10(4):975-987.
  24. Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376(18)(suppl):1748-1761.
  25. Wiersinga WM, Perros P, Kahaly GJ, et al. Clinical assessment of patients with Graves’ orbitopathy: the European Group on Graves’ Orbitopathy recommendations to generalists, specialists and clinical researchers. Eur J Endocrinol. 2006;155(3):387-389.
  26. Stan MN, Garrity JA, Bahn RS. The evaluation and treatment of Graves ophthalmopathy. Med Clin North Am. 2012;96(2):311-328.
  27. 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.
  28. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26(10):1343-1421.