The Young Ophthalmologist Symposium at the American Academy of Ophthalmology 2020 Virtual meeting detailed some of the technological advancements that have occurred in 2020 driving changes in the future of ophthalmologic treatment paradigms. During the session, Raymond S. Douglas, MD, PhD, director of the Thyroid Eye Disease Program at Cedars Sinai, was asked to tell young ophthalmologists what they need to know about teprotumumab – which was approved in January 2020 for the treatment of thyroid eye disease (TED) — in a three-minute presentation.
The inflammation and tissue remodeling associated with TED starts very early in the disease process and forms the basis of the clinical manifestations, Dr. Douglas explained. There is increased pressure in the fixed bony orbit from the short-term inflammation but also the long-term accumulation of hyaluronan and expansion of fibroblasts.
TED is driven by autoantibody activation of the IGF-1 receptor.
“We know that the IGF-1 receptor is overexpressed in TED orbital fibroblasts and activation of this receptor stimulates the release of cytokines and the production of hyaluronan,” Dr. Douglas said.
Teprotumumab is a fully human monoclonal antibody inhibitor of the IGF1- receptor. It binds to the IGF1-recpetor and TSHR signaling complex. It halts the IGF-1 receptor and TSHR signaling at the TED source, reducing inflammation and reversing retro-orbital tissue expansion and hyaluronan production.
Clinical studies of teprotumumab included a phase-2 and phase-3 study published in The New England Journal of Medicine. In these studies, teprotumumab demonstrated remarkable reduction on proptosis, reducing proptosis quickly, and, in most patients, achieving a reduction of greater than 2 mm proptosis at just two infusions. Eventually, the drug reduced proptosis by 3 mm compared with minimal change for placebo. The drug is administered over 8 infusions over 24 weeks with no further infusions unless there is a relapse.
Imaging from the studies demonstrates improvement in muscle volume and fat stranding. This is in contrast to steroids, Dr. Douglas said, which do not generate any change in proptosis.
Double vision was also greatly improved in patients receiving teprotumumab. Nearly 70% of patients had improvement of diplopia during this time period.
The overall safety profile was good. The majority of treatment-emergent adverse events were mild to moderate and none led to treatment discontinuation.
Finally, durability of teprotumumab was good. The majority of responders at 24 week retained response at week 72.