Teprotumumab has shown great efficacy in treating thyroid eye disease in both clinical trials and real-world settings, but more data are needed on adverse events, said Shoaib Ugradar, MD, UCLA Stein Eye Center Santa Monica.
Teprotumumab has shown great efficacy in treating thyroid eye disease in both clinical trials and real-world settings, but more data is needed on the adverse events of the therapy, said Shoaib Ugradar, MD, UCLA Stein Eye Center Santa Monica.
Teprotumumab is the first approved therapy for thyroid eye disease (TED). What is the impact it has had on TED and patients with the disease?
That's an excellent question, and it concerns most of the research that I've been involved in over the past few years. Now, the backstory for teprotumumab goes over the last 3 decades, wherein researchers found that there was an increase in the IGF-1 [insulin-like growth factor type 1] receptor pathway in patients with a thyroid eye disease. This led to some work that showed that this pathway directly results in increased inflammation and soft tissue expansion in these patients and causes many of the signs and symptoms that we see in terms of lid changes or proptosis and double vision.
Now, teprotumumab is a monoclonal antibody that was developed to directly target this pathway. And in the trials, in phase 2 and 3 trials over the past 5 years, it has shown great efficacy in reducing soft tissue swelling, especially behind the eyes, and in some of the work that I presented earlier this week [at the November 2021 American Society of Ophthalmic Plastic & Reconstructive Surgery meeting], across the entire face. It also reduces the disabling features of double vision and also the annoying features of inflammation.
Now, the reason teprotumumab works so well is it's a specific target of the pathogenesis of thyroiditis—ie, the IGF-1 receptor pathway. And it's very exciting for us because it also provides a key insight into the tissues that are affected by thyroid eye disease. So, I envision that in the future, much of the thyroid eye disease treatment paradigm will focus around IGF-1 blockade.
The pivotal trials for teprotumumab have small patient populations. Are larger studies needed? Would they offer additional insights?
If you look at the initial phase 2 and phase 3 trials, the combined numbers come up to I'd say about 60 or 70 patients. And you know, let's remember that the phase 3 trial was a very powerful randomized control study with compelling results and robust statistics. The fruits of that are that in the real world, when other centers have used teprotumumab once it's been released, they found similar features; for example, a similar efficacy or impact on the core aspects of thyroid eye disease. For example, a significant reduction in inflammation, proptosis, and diplopia. So, I wouldn't be too worried about the numbers in the initial sort of trials.
Now, one aspect of teprotumumab therapy that requires further numbers is related to adverse events. And I think with more people being treated with teprotumumab, we’ll learn more about the true incidence and prevalence of the adverse events. For example, hearing disturbance.