Thyroid Eye Disease Treatment Shows Long-Term Effectiveness

Raymond Douglas, MD, PhD, director of the orbital and thyroid eye disease program, Cedars-Sinai Medical Center, discusses the treatment efficacy of Tepezza (teprotumumab) in a variety of patients with thyroid eye disease, including how this treatment has shown long-term improvement in symptoms such as double vision and eye bulging. 

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Welcome back to PopHealth Perspectives, a conversation with the Population Health Learning Network where we combine expert commentary and exclusive insight into key issues in population health management and more.

Today, we are joined by Dr Raymond Douglas, director of the Orbital and Thyroid Eye Disease Program at Cedars-Sinai Medical Center. He discusses the treatment efficacy of teprotumumab in a variety of patients with thyroid eye disease, including how this treatment has shown long-term improvement in symptoms such as double vision and eye bulging. Dr Douglas?

Hi, I'm Dr Raymond Douglas, and I'm the director of the Orbital and Thyroid Eye Disease Program at Cedars-Sinai Medical Center here in Los Angeles. I also have a private practice here in Beverly Hills. Most of my practice is devoted to the care of patients with thyroid eye disease.

We have about a 15-year history in both the basic science and clinical research, both for the mechanisms that underlie thyroid eye disease and novel treatments for patients. My pleasure to contribute today and to this research.

What existing data led you and your coinvestigators to conduct this research?

We've known that Tepezza, or teprotumumab, is an IGF-1 receptor-blocking agent and had shown significant success in publications for the treatment of thyroid eye disease.

In fact, in those early studies that were published in the New England Journal, it demonstrated that at 24-week periods, that this could reverse the disease quite significantly, and the eye bulging, especially, that's associated with this disease.

Based upon that data, we wanted to pull the overall data for the treatment effect across studies, and also to look at the long-term improvement for these patients. We wanted to determine various things, such as, is there any differential response? How long does the treatment seem to be effective? Etc. That was the impetus for the treatment.

Teprotumumab has changed the landscape, how thyroid eye disease is being treated. It's very timely research to expand our knowledge in this area.

Please briefly describe your study and its findings. Were any of the outcomes particularly surprising?

The study was a pooled analysis from two large studies looking at 84 patients who had received teprotumumab and 87 patients who had received placebo. These patients were given teprotumumab early in their disease course.

It demonstrated, quite strikingly, that there was an improvement in the proptosis and in the various outcome measures for thyroid eye disease at the conclusion of therapy. In fact, the vast majority of patients achieved at least two millimeters of proptosis reduction.

About 77% of those patients in the teprotumumab group compared to just 15% in the placebo group. A dramatic and striking difference. These differences also held true for the improvement of double vision that was also strikingly improved, and overall response.

These were incredibly powerful conclusions. This appeared to work whether patients were older or whether they were tobacco users, which has sometimes confounded data, but the treatment was effective.

The most surprising outcome, and reassuring also, was that when we look at patients who had completed treatment, either after seven weeks of treatment or even almost a year, 51 weeks after treatment, these patients had a long-term improvement.

The vast majority, 87% of the patients, had an improvement in their proptosis at seven weeks and 67% that maintained out nearly a year after treatment. The results for double vision were also equally encouraging that this is leading to a long-term improvement for patients.

Reassuringly, there were no new adverse events presented in this data and that it appears that each of the adverse events or side effects were mild to moderate and were well-controlled throughout the study.

What are the possible real-world applications of these findings in clinical practice?

This is the largest, now, compilation of data using teprotumumab as a treatment. As I said, there was already great enthusiasm that teprotumumab was becoming a first-line treatment. It is the only FDA-approved treatment for thyroid eye disease.

This, in my terms, throws gasoline onto the fire, in that it gives us great data. A, that there is a significant effect of teprotumumab in the reduction of proptosis and improvement in double vision, things that were impossible to improve before.

Secondly, it gives us great reassurance that this is a long-term result and that there are no new safety findings that are being uncovered, that this appears to be a safe and effective therapy for the treatment of thyroid eye disease. The Lancet was wonderful in helping to spread the word that this is a quite pivotal therapy in the treatment of this disease and moving forward.

Do you and your coinvestigators intend to expand upon this research?

Yes. There's certainly areas in which this can be expanded. For example, one of the things that is important and was part of the trials is that these were primarily patients who were treated in the early stages of disease.

We're now compiling evidence and we've even recently published a paper that even in later stages of the disease, that teprotumumab can be quite effective at reducing the proptosis and the double vision caused by this disease.

I think that that will warrant and is going to warrant a formal study to looking that there's broad implication, not just for early disease, but also in later-phase disease. In addition, how this impacts patients' quality of life in various ways will also be examined. There was quite a significant improvement in quality of life noted in this study.

That speaks to the profound effect that this drug is having for patients, but I think that could warrant further exploration as we move along. Also, discerning if there were any patients who did not respond. Could they require a longer treatment period? Etc. That question will also be addressed in the future.

There are some questions, but this certainly is the sword that is leading the way and pushing forward this unique mechanism and hopefully, a wonderful treatment for our patients who have been left without much in the past for thyroid eye disease.

Is there anything else pertaining to your research and findings that you would like to add?

The biggest question that this moved forward was that teprotumumab appears to work in all patient subgroups in these trials in the largest theories that we've put together and that they maintain these results in the long term. That is key and critical.

Hopefully, we're going to see that this translates into not having patients undergo deformative surgeries, where we drill out the bone behind their brain, but can offer them a medical therapy that transforms their disease.

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