Teprotumumab for Moderate to Severe Thyroid Eye Disease

If thyroid eye disease (TED), an autoimmune disease that may affect the appearance and function of one or both eyes, is moderate to severe, eye drops and comfort measures may not be enough. It may be necessary to target the inflammation and swelling behind the eyes that can cause bulging, double vision, or vision-threatening pressure on the optic nerve.

What Is Teprotumumab?

Teprotumumab is a monoclonal antibody, a lab-made protein designed to target a specific pathway involved in TED.

“Teprotumumab can be very effective at reducing proptosis, the appearance of bulging eyes that occurs in TED,” says Nathan T. Tagg, MD, a neuro-ophthalmologist at Duke Eye Center in Durham, North Carolina. In some people, it can also help with strabismus, or eye misalignment, and can help relieve compression of the optic nerve in more severe cases, he says.

TED develops when inflammation and immune activity affect the tissues around the eyes. Certain cells in the eye socket, called fibroblasts, can become overactive and contribute to swelling, tissue expansion, and eye bulging.

Teprotumumab blocks the insulin-like growth factor 1 receptor, or IGF-1R, says Tagg. “Blocking that receptor decreases fibroblast activity, which is important in the development of TED,” he says.

When Is Teprotumumab Used to Treat TED?

For moderate to severe TED, teprotumumab may be one part of a multipronged approach to treatment.

Depending on your symptoms, Tagg says care may also include:

• Treatment for dry eyes, irritation, or exposure symptoms
• Smoking cessation, because smoking is linked with worse TED
• Prisms or surgery for strabismus, or eye misalignment
• Surgery if pressure on the optic nerve threatens vision
• Ongoing care from both an ophthalmologist and an endocrinologist

“We generally don’t select more than one medication-based treatment at a time,” says Tagg, meaning your doctor may weigh teprotumumab against other medication options instead of adding it on top of another systemic TED drug.

The decision depends on how active the disease is, how severe the symptoms are, whether vision is at risk, what treatments have already been tried, and which side effects are most concerning for you, he says.

When Tagg talks with patients about teprotumumab, he frames both the possible benefits and the risks.

Teprotumumab can be expected to calm the inflammatory response in the orbit and help shrink inflamed tissues, he says. “This leads to decreased proptosis, increased comfort, and in some cases decreased double vision or vision loss.”

The risks need careful discussion, especially hearing changes. “There is a real risk of hearing loss, probably on the order of 10 to 25 percent, and this hearing loss can sometimes be permanent.”

For that reason, Tagg says he is hesitant to use teprotumumab in someone who already has hearing loss. Teprotumumab can also make diabetes harder to treat and cause painful muscle cramping, he says.

Before starting treatment, ask what monitoring you need, especially if you have diabetes, prediabetes, hearing problems, inflammatory bowel disease, or could become pregnant.

Is Teprotumumab a Cure for TED?

Teprotumumab can make a meaningful difference for some people with TED, especially when eye bulging is a major concern, but it’s not considered a cure.

In clinical trials, teprotumumab improved several TED symptoms and measures, including eye bulging, double vision, inflammation, and quality of life. A follow-up analysis of three trials found that many patients still had benefits after treatment ended:

• About 68 percent still had improvement in eye bulging at week 72.
• About 73 percent still had improvement in double vision at week 72.
• About 66 percent still had an overall response, meaning they had improvement in both eye bulging and inflammation.
• About 82 percent did not report needing additional TED treatment through 99 weeks after therapy.

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If you are considering teprotumumab, ask your doctor what symptom the drug is meant to improve and how you will know if it is working.

Useful questions include:

• Am I being treated mainly for eye bulging, double vision, inflammation, or optic nerve pressure?
• How will you monitor my response during treatment?
• What hearing or blood sugar monitoring do I need?
• What side effects would make you stop treatment early?
• If my symptoms return, would retreatment, steroids, surgery, or another medication be considered?

What’s Ahead for TED Treatment?

TED treatment is changing quickly. Teprotumumab opened the door to targeted TED therapy, and new options may give doctors more ways to tailor treatment.

“Off-label drugs that target other parts of the inflammatory cascade have also been studied including rituximab, tocilizumab, and mycophenolate mofetil, for example,” says Tagg. These are sometimes prescribed when teprotumumab or corticosteroids are not effective or tolerated, he adds.