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After thyroid eye disease (TED) is diagnosed and patients are started on initial treatment options, clinicians next have to focus on long-term management of the condition.

"Long-term care for TED often requires a team of doctors," said Terry J. Smith, MD, of Kellogg Eye Center at the University of Michigan in Ann Arbor, noting that the disease is both serious and progressive.

Comprehensive Care Is Key

Because up to half of patients with Graves' disease typically go on to develop TED, long-term patient care should be co-managed by an endocrinologist and TED eye specialist, Smith told 麻豆传媒.

"Eye specialists managing TED can include oculoplastic surgeons, neuro-ophthalmologists, strabismus ophthalmologists, or optometrists who specialize in diagnosing and treating TED," he said. "I recommend that all patients with Graves' disease undergo a baseline comprehensive eye exam with an eye specialist and follow up with a specialist at the first sign of any eye symptoms."

Mark Krakauer, MD, MPhil, of the Lewis Katz School of Medicine at Temple University in Philadelphia, said that when he initially sees a patient with TED, the first thing he does is determine exactly what the disease is affecting.

"I try to determine if the disease process is affecting their orbital fat, their eye muscles, or the position of the eyelids, amongst other things, and whether they have signs of active inflammation," he told 麻豆传媒. "Their characteristics determine whether surgical treatment, including possibly orbital decompression, eye muscle, or eyelid surgery, is indicated."

"The most feared complication of thyroid eye disease is irreversible vision loss, which is caused by compression of the optic nerve," Krakauer pointed out. "Thankfully this can be detected and treated if the patient is seen promptly by an eye specialist."

"Patients may experience double vision, which can be treated with eye muscle surgery. Patients may also be bothered by the appearance of the eyes, and this can sometimes improve over time, or with surgery," he added.

It's important to watch for disease flare-ups over time as TED is a serious, progressive disease that can potentially lead to blindness if left untreated, Smith warned.

This long-term management approach often depends on whether TED is mild, moderate, or severe, Terry Davies, MD, of the Icahn School of Medicine at Mount Sinai in New York City, explained to 麻豆传媒.

Adding to this, Krakauer said: "On one end of the spectrum, the patient may only need to be managed with eye drops, or at the other end of the spectrum, they may need all three types of surgeries over the course of a few years."

But prior to undergoing surgical intervention, other treatment options like steroids, radiation therapy, or the monoclonal antibody teprotumumab (Tepezza) are available. Teprotumumab, which is the only non-surgical, FDA-approved treatment for TED is administered in eight doses: dosed as 10 mg/kg for the first infusion, followed by 20 mg/kg every 3 weeks for seven additional infusions.

Underpinning this approval were the positive phase II and phase III OPTIC findings, which found an average 2.82 mm reduction in proptosis after 24 weeks of teprotumumab infusions in patients with active TED.

Smith added that this new treatment option has single-handedly "changed how clinicians treat TED."

"Tepezza is the first drug available which can improve the eye bulging, and in some patients is remarkably effective," said Davies, who pointed out that persistence of bulging of the eyes, double vision, and swelling around the eyes are three of the most common long-term problems associated with TED.

"In the long term, the eyes may improve or remain a problem -- with obvious bulging, double vision, and cosmetic problems from edema around the eyes. Once the disease inflammation settles, then any corrective surgery can be planned," he said.

New Age of Non-Surgical Treatments

With the success of teprotumumab, there's been a big shift towards researching more about nonsurgical treatment options for TED.

"Currently, Tepezza is being evaluated for patients with long-term eye signs who have not been treated earlier, and it appears to be effective," noted Davies.

Since the drug's approval, some other post-marketing studies have continued to show long-term efficacy in managing TED. In the open-label extension clinical trial, patients who had TED for a longer median duration -- 12.9 months versus 6.3 months in the original trial -- also yielded significant benefit after infusion, with those who responded to treatment showing an average proptosis reduction of 3.5 mm. A total of 90.6% maintained this proptosis response by week 48, which was 27 weeks after their last dose.

More recently, developer Horizon announced that a is now underway, testing the agent in TED patients with a low baseline clinical activity score (CAS), a measure of inflammatory symptoms, with findings expected in mid-2023.

This is only the beginning of possible new treatment options for this chronic and complex condition, as there are several possible new treatment options being developed -- some already in phase III trials -- said Davies.

"These may work with Tepezza or may work alone, but only time will tell," he said. "Hopefully some will work for all patients with Graves' disease and not just those with bad eye involvement."

Echoing this sentiment, Smith added: "I am hopeful that these [new clinical trials] will result in additional treatment options for patients. This increasing understanding of TED and Tepezza has opened the door to new research."

One of these new investigational agents currently being investigated is the anti-IGF-1R antibody , developed by Viridian Therapeutics.

The investigational agent has already shown promise in a phase I/II trial using the same efficacy endpoints that were used in the teprotumumab trials. The initial data found a 2.4 mm mean reduction in proptosis from baseline at week 6 with an 83% proptosis responder rate, defined as a 2 mm or greater reduction in proptosis.

A CAS of 0 or 1 was also achieved by 83% of patients, marked by a mean reduction of 4.3 points from baseline.

The phase III THRIVE trial is expected to kick off at the end of this year in patients with both active and chronic TED.

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