Tepezza offers a way to treat its root cause.

Until recently, physicians had to stand by while their patients with thyroid eye disease (TED) suffered through a series of debilitating symptoms before the disease stabilized enough for surgical intervention. Fortunately, with the January 2020 FDA approval of Tepezza (teprotumumab-trbw, Horizon Therapeutics), that waiting game has come to an end.

“I would say to patients all the time, ‘The hardest thing about this disease is for us to sit on our hands and watch and wait and let you go through this while we’re waiting for your disease stabilize,’” says Andrew R. Harrison, MD, associate professor of ophthalmology and otolaryngology at the University of Minnesota Medical School, Minneapolis, and codirector for the Center of Thyroid Eye Disease. “Now we have a drug to treat the inflammation and the disease process at its root cause. We’re not waiting for the disease to burn out and then treat the patient. With Tepezza, we can basically stop the autoimmune process that’s going on in the orbit at its cause.”

PHYSICAL AND MENTAL DISTRESS

With a prevalence of about 19 out of 100,000 individuals, TED affects women more than men but tends to be more severe in men, says Dr. Harrison.^1,2 As an autoimmune response to the tissue behind the globe, the most common sign (seen in 90% of patients) is eyelid retraction. Some 60% of patients with TED will also have bulging (proptosis), and 50% will have double vision (diplopia), he notes.³

But the impacts of the disease don’t stop there. “It really affects your appearance to the point that you don’t look like yourself anymore,” says Dr. Harrison, who has 23 years of clinical experience treating TED patients. He notes that patients with TED score on anxiety and depression scales at levels equal to patients with breast cancer.

“So, it’s not only a physical disorder, but it affects their mental health,” he explains. “The quality of life is really poor for these folks.^4,5 It really affects all facets of a patient’s life.”

Paul Phelps, MD, FACS, founder of Chicago Oculofacial Plastic Surgery, Chicago, agrees. “Almost as much as the double vision bothers them, their physical appearance bothers them.”

UNDERSTANDING THE COURSE OF TED

In general, patients experience an acute phase that can last 18 months to 3 years followed by a chronic phase in which the disease stabilizes, says Dr. Harrison. At that point, the patient could start a series of surgeries on the eye socket, eye muscles and eyelids to attempt to restore function and have them appear as they did before the disease, he explains. Steroids could be used to quell the inflammation in the acute phase.

“But in general, it was watch and wait, and then perform surgical procedures,” says Dr. Harrison.

TEPEZZA IN THE PRACTICE

An insulin-like growth factor-1 receptor (IGF-1R) inhibitor, Tepezza is administered via infusion. It blocks IGF-1R and lessens proptosis by reducing inflammation and preventing muscle and fat-tissue remodeling as well as tissue expansion behind the eye.

Dosing is initiated with 10 mg/kg for first infusion followed by 20 mg/kg every 3 weeks for seven additional infusions, according to the prescribing information. Tepezza is the only FDA-approved treatment for TED.

In two studies completed before FDA approval, researchers found that 90% of the patients had a 2-mm or more improvement in proptosis and 60% had improvement in diplopia, with 50% having complete resolution of diplopia, according to Dr. Harrison. Some two-thirds of patients showed significantly decreased inflammation.^6,7

“The treatments for TED before Tepezza were not nearly as good,” says Dr. Phelps. Ultimately, almost all TED patients with proptosis or diplopia required surgery, and “now many of them don’t require surgery. I typically recommend Tepezza as a first-line treatment for patients with moderate to severe proptosis and diplopia. This drug is great for patients who otherwise didn’t have a good option before.”

In general, notes Dr. Phelps, in measuring the clinical activity score and how active TED is, “it’s almost always fully resolved with the treatment of Tepezza.” If proptosis and eyelid retraction don’t fully resolve, “the surgery to fix what remains is much easier than it would have been without treatment,” he notes.

The drug can be effective in chronic patients as well. In two studies of chronic patients, 90% had improvement in proptosis and significant improvement of 3-4 mm in bulging, notes Dr. Harrison.^8,9 “These patients are having responses equal to surgery with this drug,” he says. In addition, he says that evidence is mounting that Tepezza can be used for patients with compressive optic neuropathy.

LOOK SHARP

Dr. Harrison urges ophthalmologists to be mindful of TED. If treating a patient with red, irritated, scratchy eyes, the cause might not be dry eyes or conjunctivitis. “Look closely at their eyelids and their muscle movement. Perhaps they have underlying TED. It can present fairly insidiously. The most important thing is recognizing the disease.” OM

Disclosures: Dr. Harrison is a consultant and speaker for Horizon Therapeutics. Dr. Phelps is a speaker for Horizon Therapeutics.

REFERENCES

1. Lazarus JH. Epidemiology of Graves’ orbitopathy (GO) and relationship with thyroid disease. Best Pract Res Clin Endocrinol Metab. 2012;26:273-279. doi: 10.1016/j.beem.2011.10.005. https://www.sciencedirect.com/science/article/abs/pii/S1521690X11001321 . Accessed June 30, 2022.
2. Perros P, Crombie AL, Matthews JN, Kendall-Taylor P. Age and gender influence the severity of thyroid-associated ophthalmopathy: a study of 101 patients attending a combined thyroid-eye clinic. Clin Endocrinol (Oxf). 1993;38:367-372.
3. Bothun ED, Scheurer RA, Harrison AR, Lee MS. Update on thyroid eye disease and management. Clin Ophthalmol. 2009;3:543-51. doi: 10.2147/opth.s5228. Epub 2009 Oct 19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2770865 . Accessed June 30, 2022.
4. Cockerham KP, Padnick-Silver L, Stuertz N, et al. Quality of Life in Patients with Chronic Thyroid Eye Disease in the United States. Ophthalmol Ther. 2021 Dec;10:975-987. doi: 10.1007/s40123-021-00385-8. Epub 2021 Sep 3.PMID: 3447812.6
5. Farid M, Roch-Levecq AC, Levi L, et al. Psychological disturbance in graves ophthalmopathy. Arch Ophthalmol 2005 Apr;123:491-496.
6. Douglas RS, Kahaly GJ, Patel A, Sile S, et al. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020 Jan 23;382:341-352. doi: 10.1056/NEJMoa1910434.PMID: 31971679 Clinical Trial. https://www.nejm.org/doi/full/10.1056/NEJMoa1910434 . Accessed June 30, 2022.
7. Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, et al. Teprotumumab for thyroid-associated ophthalmopathy. .N Engl J Med. 2017 May 4;376(18):1748-1761. doi: 10.1056/NEJMoa1614949. https://www.nejm.org/doi/full/10.1056/NEJMoa1614949 . Accessed June 30, 2022.
8. Ugradar S, Kang J, Kossler AL,et al. Teprotumumab for the treatment of chronic thyroid eye disease. Eye (Lond). 2021 Jul 9. doi: 10.1038/s41433-021-01593-z. Online ahead of print. https://www.nature.com/articles/s41433-021-01593-z . Accessed June 30, 2022.
9. Teprotumumab for chronic thyroid eye disease. Ozzello DJ, Dallalzadeh LO, Liu CY. Orbit. 2021 Jun 1:1-8. doi: 10.1080/01676830.2021.1933081. Online ahead of print. PMID: 34060414.