Disclosures: Smith reports being issued patents in the U.S. for teprotumumab in the treatment of thyroid eye disease. The patents are held by the Lundquist Institute at Harbor-University of California Los Angeles Medical Center. Smith serves as a consultant for Horizon Therapeutics.
September 20, 2021
3 min read
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Should teprotumumab become first-line therapy for thyroid eye disease?

Disclosures: Smith reports being issued patents in the U.S. for teprotumumab in the treatment of thyroid eye disease. The patents are held by the Lundquist Institute at Harbor-University of California Los Angeles Medical Center. Smith serves as a consultant for Horizon Therapeutics.
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POINT

With the development and FDA approval of teprotumumab, it is likely that drug will become first-line therapy.

Terry Smith

Traditionally, many experts in the field have advocated steroids. More recently, EUGOGO and others have advocated high-dose pulse steroid therapy in TED as that route of administration appears to be less associated with side effects.

However, with the development and the FDA approval of teprotumumab, it is likely that teprotumumab will become first-line therapy where available. The drug dramatically improved not only the activity of the disease, but severity of the disease in a large fraction of patients who were treated.

This is the first and only drug to be approved for the treatment of TED. Steroids and other drugs like rituximab are used off-label. Those other drugs don’t reduce disease severity. Steroids, for instance, seem to calm some of the inflammatory manifestations in about half of the patients who are treated. But they do not reduce the proptosis and they do not reduce the double vision reliably. Teprotumumab does both and reduces inflammatory manifestations.

In my view, the side effect profile of teprotumumab is also superior to that of steroids. In 51-week data, after the final dose of teprotumumab, 67% of patient-responders continued to have proptosis response.

Teprotumumab is approved only in the U.S. thus far, but we suspect that it will get approved and become available elsewhere. Yes, it’s far more expensive than steroids, but teprotumumab appears to give about the same level of benefit as the best published data on rehabilitative ocular surgeries. We therefore think that ultimately, many patients will find the need for surgical rehabilitation obviated by treatment with this drug.

Terry Smith, MD, is the Frederick G.L. Huetwell Professor of Ophthalmology and Visual Sciences and professor of internal medicine at the University of Michigan Medical School.

COUNTER

Teprotumumab works, but we don’t know what the efficacy and cost are in the long run.

In Europe, this question is difficult to discuss for two reasons. One, teprotumumab is simply not yet registered here, so it cannot be the first-line therapy since we do not have access to it. The second issue is whether we would use teprotumumab if we had access.

Laszlo Hegedüs

Here, I’m a bit more hesitant than the American continent for two reasons. One is, in this context, considerable expense. We do not have studies showing whether using teprotumumab is financially sound. Is a buck well spent using teprotumumab in relation to other therapies? We do lack randomized studies comparing teprotumumab with other drugs, which I think is a huge issue. Looking at this from a socioeconomic standpoint, it may well be that teprotumumab in the long run is the cheapest therapy, but we do not know because such data are lacking. The other problem is that the studies of the alternative drugs for TED are very poor too. Few of them have been tested compared with placebo or offering no intervention. The first-line treatment in Europe currently is IV steroids, according to an algorithm that we have known for a couple of decades. We know that this has some effect, but we also know that many patients have residual complaints or recurrence. A direct comparison between steroids and teprotumumab would be a wonderful study to do. Analyzing efficacy, side-effects and socioeconomic variables would allow for comparing current European first-line therapy with the suggested American first-line option.We know that teprotumumab works. The pathophysiology of TED is acceptably characterized. Importantly, from a mechanistic point of view, the target for teprotumumab is characterized, which is not the case for most of the other drugs. Lacking long-term recurrence rate and cost-effectiveness leaves questions open to which answers are needed before offering a treatment. Finally, a major concern is the lack of defining the phenotype, in this context severity of TED, which merits treatment with teprotumumab. We need to acknowledge that this opens an avenue toward abuse, that is, the possibility of offering the treatment to those not needy. From a European perspective, this is a major concern.

Laszlo Hegedüs, MD, is a consultant physician and professor in the department of endocrinology at the University of Southern Denmark and president of the European Thyroid Association.