On this episode of Interventional Mindset, Preeya K. Gupta, MD, sits down with Prem Subramanian, MD, PhD, to discuss recent advancements in the treatment of thyroid eye disease (TED).
Dr. Subramanian is a professor of ophthalmology, neurology, and neurosurgery and vice chair for academic affairs in ophthalmology at the Sue Anschutz-Rodgers University of Colorado Eye Center and School of Medicine as well as the Clifford R. and Janice N. Merrill Endowed Chair in Ophthalmology.
Interventional Mindset is an educational series that gives eye physicians the needed knowledge, edge, and confidence in mastering new technology to grow their practices and provide the highest level of patient care. Our focus is to reduce frustrations associated with adopting new technology by building confidence in your skills to drive transformation.
Browse through our videos on a variety of topics within cataract and refractive surgery, glaucoma, and ocular surface disease to learn practical insights into adopting a variety of new surgical techniques and technology.
Encountering thyroid eye disease in the clinic
Thyroid eye disease is a rare autoimmune condition caused by the activation of orbital fibroblasts by autoantibodies directed against thyroid receptors that can result in enlargement of the extraocular muscles and fatty and connective tissue volume.1 Of note, TED has a broad spectrum of presentations that can include inflammatory ocular surface disease with dry eye symptomatology.2
As such, Dr. Subramanian explained that it is important for all ophthalmologists to understand which symptoms to consider potentially suspicious for TED, such as:3
- Chronic red or dry eye that is unresponsive to standard therapies
- Palpebral fissure
- Proptosis
- Difficulty with or incomplete lid closure (ex., lagophthalmos)
- Diplopia
He explained that many ophthalmologists are in a position to make a TED diagnosis in patients who have no history of an autoimmune thyroid disorder. In fact, “at least 20% of people with TED won’t have an autoimmune thyroid disorder, and 40% of those who develop an autoimmune disorder may present with ocular symptoms first,” added Dr. Subramanian.4,5,6
Watch the full interview to hear an in-depth conversation about the pathophysiology of TED!
Treatments for thyroid eye disease
As TED can be a debilitating condition for patients, it is critical for them to have available treatments to ease the disease burden. Until recently, the main treatment approach for TED was intravenous corticosteroids and/or orbital radiation to address the acute inflammatory phase and subsequent surgical correction, such as orbital decompression, strabismus surgery, or eyelid retraction repair, during static or quiescent phases of the disease.1
Enter TEPEZZA
However, in January 2020, TEPEZZA (teprotumumab-trbw, Amgen) became the first drug approved by the FDA for the treatment of TED.7 Teprotumumab is a monoclonal antibody directed against the insulin-like growth factor-1 receptor (IGF-1R) to block its activation and signaling.1
This aids in “preventing the cascade of inflammatory mediators that result in the deposition of glycosaminoglycans, hyaluronic acid, and other substances that lead to tissue edema and the persistent changes seen in TED,” remarked Dr. Subramanian. TEPEZZA is an infused therapy typically given every 3 weeks over a total treatment course of eight infusions.
Combined analyses of phase 2 (NCT01868997) and phase 3 (OPTIC, NCT03298867) clinical trials for TEPEZZA demonstrated significant improvements in:8
- Proptosis
- 77% of patients in the teprotumumab group (compared to 15% in the placebo group) achieved a reduction in proptosis of 2mm or more
- Clinical activity score (CAS)
- Diplopia
- Quality of life (QOL) in patients with active TED
Of note, patients in these clinical trials had a relatively short duration of disease (i.e., onset of active TED symptoms within 9 months prior to baseline) and an active status as measured by inflammatory signs and symptoms. TEPEZZA was the first intervention for TED to not only reduce inflammatory signs and symptoms (which steroids could do), but also effectively reduce proptosis, noted Dr. Subramanian.
Long-term durability of TEPEZZA
After the phase 3 clinical trial, an open-label extension study (OPTIC-X, NCT03461211) was created to evaluate the efficacy and safety of a second course of TEPEZZA. Patients from OPTIC who did not have a therapeutic response in proptosis, had a recurrence of proptosis during the follow-up period, or had previously received a placebo were enrolled.9
In total, 33 of 37 (89.2%) placebo-treated OPTIC patients became proptosis responders when treated with teprotumumab in OPTIC-X, with equivalent responses to the OPTIC study. Of the five OPTIC teprotumumab nonresponders that were retreated in OPTIC-X, two responded, one showed a proptosis reduction of 1.5mm from the OPTIC baseline, and two discontinued treatments. Further, of the OPTIC teprotumumab responders who experienced TED flares, five of eight (62.5%) patients responded when retreated.9
A further study found that the long-term response as observed 51 weeks after teprotumumab therapy was similar to week 24 results, and 82% of patients did not require further TED treatment for over 99 weeks following their final teprotumumab dose.10
To learn more about the risk of regression and which patients may benefit from retreatment, watch the full interview!
When to refer TED patients
TED is a team sport, noted Dr. Subramanian, and taking care of these patients requires collaborative and interdisciplinary care to ensure that both TED and systemic thyroid dysfunction are properly managed. He added that some TED patients can be successfully managed with conservative measures to control the disease; however, for those with warning signs, such as a rapidly progressing disease, a consultation with a TED specialist is warranted.
Some signs of fast-progressing TED include:
- Significant increase in proptosis over a short period of time
- Periorbital edema
- Eyelid retraction
- Diplopia
As a cornea specialist, Dr. Gupta highlighted that when she sees patients with superior limbic keratoconjunctivitis and other inflammatory signs, she begins to suspect that they may have thyroid dysfunction.
Conclusion
Early referral and coordinated care are key to managing thyroid eye disease. Fortunately, with the approval and implementation of TEPEZZA, there is yet another intervention available to ophthalmologists to tailor the treatment approach for TED patients to optimize outcomes.
