Researcher highlights new treatments for thyroid eye disease
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CHICAGO — Thyroid eye disease, a condition most commonly associated with Graves’ hyperthyroidism, typically comes with a range of symptoms that can make everyday tasks challenging and quickly reduce quality of life. Within 18 months of a diagnosis of Graves’ disease, approximately 25% of patients will develop thyroid eye disease, with symptoms including proptosis, the main cause or morbidity, as well as eyelid retraction, strabismus and, occasionally, compressive optic neuropathy.
In a presentation at the American Thyroid Association annual meeting, Marius N. Stan, MD, an endocrinologist with Mayo Clinic in Rochester, Minnesota, highlighted some of the latest developments in thyroid eye disease research, including an experimental human monoclonal antibody shown to dramatically reduce the most debilitating symptoms of Graves’ orbitopathy, namely proptosis and double vision.
Endocrine Today spoke with Stan about the signs and symptoms of thyroid eye disease, available treatments and new agents in the pipeline that may offer patients exciting new options.
Thyroid eye disease is most often associated with Graves’ disease. What do endocrinologists need to know?
Thyroid eye disease is associated most of the time with Graves’ disease, but it is also associated with Hashimoto’s thyroiditis, which most people know as hypothyroidism, and it also develops in people with, to their knowledge, no thyroid disease whatsoever. To link thyroid eye disease only with Graves’ disease excludes those smaller categories. Keep in mind that there may not be Graves’ disease, per se. If there is association with Graves’ disease, the thyroid eye disease tends to develop very soon after the diagnosis.
What are the most common symptoms a person with thyroid eye disease might experience?
Most patients will notice a little bit of eye irritation. They may complain of dry eye or a feeling of sand under the eyelid. The eyelids become red or swollen. The look of the eye may change, with the upper eyelid sort of pulled up, and that may be because of hyperthyroidism or the eye is slightly pushed forward. There may be discomfort behind the eye. Many times, patients start with the idea that this must be an allergic reaction. It is misdiagnosed many times as an allergy and treated as such for weeks to months at a time. Over time, the persistence of the disease, along with the associated thyroid findings, lead the physician to the correct diagnosis. This also has to do with the fact that not all physicians are familiar with this disease. It is relatively uncommon for the general practitioner. But as the ophthalmologist gets involved, the level of familiarity with the disorder is more likely to lead to the correct diagnosis. If there is known thyroid disease, it is more likely the patient will get the correct diagnosis from the beginning.
What is quality of life like for these patients?
Quality of life is affected from multiple angles. The most important aspect, I would say, is functional. Double vision is a prominent problem and it leads to many individuals having difficulty with using electronic equipment. Many have difficulty driving, and particularly all the symptoms are more difficult to handle at night. Even those able to drive initially have to give up evening driving because the lights are troublesome to handle. Some of these individuals use sunglasses all day long. There is a constant need to use lubrication for the eye. The other aspect is manipulating fine machinery, anything that needs precision.
At the other end is the social aspect. It is a very noticeable change for those around you. People report discomfort in social situations. They feel it’s a point of attention.
What have we used to treat so far and what is on the horizon now?
The disease has a few levels of severity. At the low end, fortunately, local treatment suffices. This can include artificial tears during the day and prolonged applications of gels or ointments at night. These can have a cooling or calming effect on the lining of the eye. Beyond that, people may use sunglasses or goggles, which help the eyes to retain moisture. These local treatments are helpful.
When double vision is present, an early therapy could be prisms inserted into the eyeglasses, but you can only go so far with this. Selenium is something touted as a helpful drug for patients with mild disease to decrease inflammation.
As the disease gets more severe, that is when IV steroids become the dominant player. This has been successful in clinical trials, but not very effective in the long run in practice. It leads a number of patients to feel there is a benefit, but it is a transient benefit for a significant percentage of them. IV steroids come with their own side effects, so they are not a desirable choice. That is why these days when we hear about thyroid eye disease, it is exciting because we finally have some new treatments on the horizon.
The top of the line agent is teprotumumab (Horizon Therapeutics). This drug is interacting with the IGF-I receptor and is able to not only decrease the inflammation but also significantly decrease the proptosis, and also improve quality of life and the double vision. From all angles, it seems to be a very effective agent.
You are giving a talk at ATA about treatments for thyroid eye disease. What might be most surprising to the audience?
Teprotumumab is just one of a number of drugs being considered. If attendees come to the session without a lot of knowledge on teprotumumab, they will be impressed with what this drug can achieve. We have to be careful: From case series to clinical trial and then to practice, there seems to be a decrease in the amplitude of the results for any therapy. So, this drug seems to achieve a lot, and we hope that it will remain at the same level of efficacy as we start to use it in practice. It has not been approved anywhere yet, but it is going through the FDA regulatory process as we speak. I expect we will have an answer from the FDA early next year.
There are also a number of drugs that have not made that big of a wave yet. Some are being tested for Graves’ disease. We will learn a lot more in the next few years about these other drugs, which can affect the antibodies that are very likely the reason for the thyroid eye disease itself. The immunosuppressive drug tocilizumab (Actemra, Genentech), for example, which is already approved in the U.S. for rheumatoid arthritis, is not as potent as teprotumumab, but we’ll have to see if there is a benefit for combining these two agents down the road. K1-70, a thyroid-stimulating hormone receptor antagonist, iscalimab, a CD-40 pathway inhibitor, ATX-GD-59, a tolerogenic "vaccine," as well as small molecule inhibitors to the TSH receptor as well as small molecule inhibitors like the novel, highly selective thyrotropin receptor inhibitor S37a, are other treatments in the pipeline that show promise for treating this disease. These developments will continue to change this field in a positive direction.
What else should endocrinologists keep in mind?
Treatment of thyroid eye disease has to include eliminating the known risk factors, namely, smoking and abnormal thyroid levels. For every case — be it mild or most severe — these have to be up front. Smoking is a tough one to handle, but it is clear that patients who remain smokers and are treated with the best tools today still fare less well vs. those who are nonsmokers. Similarly, hyperthyroidism and hypothyroidism have a negative impact on thyroid eye disease. These should be discussed and optimized. – by Regina Schaffer
Disclosure: Stan reports no relevant financial disclosures.