Teprotumumab has been game changer in management of thyroid eye disease
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Thyroid eye disease is a debilitating, inflammatory autoimmune condition associated with Graves’ disease that is hard for patients, both physically and psychologically.
When you think about an acute disease such as bacterial pneumonia, patients have rapid onset of symptoms, are prescribed an antibiotic, and are usually on their way to being better after a 10-day course. Patients understand and tolerate these types of medical issues.
Thyroid eye disease, however, has its onset over the course of weeks and months, often with vague inflammatory signs in the beginning. The acute and chronic inflammation from this autoimmune process debilitates a patient’s function and appearance, some worse than others. The overexpression of various antibodies, including TSH receptor and insulin-like growth factor receptor, upregulates a whole inflammatory cascade. This results in fibroblast activation, adipogenesis, glycosaminoglycan deposition with an osmotic gradient and subsequent edema as well as the overlying inflammation from lymphocyte activation.
If we go back a few years before Tepezza (teprotumumab-trbw, Horizon Therapeutics), patients with mild disease would just be monitored, and we would try to maximize their endocrinology management for underlying thyroid issues. We also knew that smoking cessation was key to reducing periocular inflammation, and even selenium supplementation could help. If patients had more moderate or advanced disease, we would often put them on IV steroids at high doses, but that came with increased morbidity as well as the potential for increased mortality at these doses.
Steroids and other immunologic therapies worked transiently during the dosing, but they did not typically change the endpoint of the disease. If people had prominent eye issues such as proptosis, double vision, significant lid retraction or chronic swelling, the steroids may have made them feel better while they were on the medication, but it did not reverse the disease in most patients. It just calmed things down while on therapy. Then, when you stopped it, the disease still had the potential to smolder and flare before gradually burning out. Patients were left with permanent orbital remodeling, fibrosis, potential diplopia and disfigurement. From a psychological standpoint, patients were very much concerned about their loss of function and change in appearance as things progress.
It was always frustrating with thyroid eye disease because it seemed like we were just trying to keep it at bay, hoping it did not explode. Then, once the disease burned out and calmed down, we would go back and surgically rehabilitate the area and try to improve the proptosis, strabismus or lid position, often with several surgeries. You could certainly rehabilitate these patients, but it was a long road. You are waiting a year or two for things to calm down before you start doing surgeries unless there is an acute indication, such as compressive optic neuropathy, where you need to jump in and intervene sooner than later.
When teprotumumab came on the market, it was the first new medication in the world of oculoplastics that changed the way we manage a disease in decades. Now, we understand the biology of the inflammatory cascade within the orbit that leads to swelling, chronic inflammation and fibrosis within the orbital fat and extraocular muscles. We are all familiar with the proptosis, strabismus and disfigurement. By exploiting our knowledge of the inflammatory cascade and the receptors within the cells that get activated in this disease, physicians can utilize medications to turn off those processes and stop them cold.
Teprotumumab works as it is an insulin-like growth factor receptor inhibitor, an important part of the disease pathway. Not only does it turn off the inflammatory process, but it also reverses a lot of the findings. It is the one treatment that reverses proptosis and reduces strabismus. It can even relieve compressive optic neuropathy for patients with severe disease.
Of note, when the drug first went through clinical trials, the inclusion criteria were quite tight — new-onset disease within 9 months, thyroid function under control, active inflammation — and that was often used to determine who was eligible for the drug under insurance plans. It became a bit frustrating trying to get patients precertified because a lot of patients do not get their diagnosis until after month 9 or missed some other inclusion criteria as defined by the initial study. Fortunately, more and more data are coming out regularly that continue to prove the efficacy of this medication in multiple stages of the disease. Now that the drug has been out longer, we are starting to see that it has a place in reversing the disease in the acute setting, the chronic setting and even down the road after the disease has seemingly burned out. As with any medication, there is some potential for side effects that require ongoing monitoring. Finally, as the immunology and cellular processes continue to be studied, there are additional medications actively in clinical trials that may be added to the toolbox for this previously challenging problem.
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- Scott M. Goldstein, MD, is a pediatric and adult oculofacial plastic surgeon at Tri-Century Eye Care in Pennsylvania and an adjunct associate professor of ophthalmology at the University of Pennsylvania’s Scheie Eye Institute.
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