The field of thyroid eye disease (TED) is finally beginning to evolve. According to Erin Shriver, MD, clinical professor in the Department of Ophthalmology and Visual Sciences at the University of Iowa Carver College of Medicine, traditional therapies, with their sometimes limited success, are giving way to new drugs that may deliver lasting benefits to patients. in Iowa City.
Teprotumumab (Tepezza; Horizon Therapeutics), a human monoclonal antibody against the IGF-1 receptor that received FDA approval in 2020, is effective in treating patients with moderate to severe PDD who have been diagnosed within 9 months following the planned start of treatment. Infusions of the drug are done every 3 weeks over 6 months for a total of 8 infusions.
Teprotumumab Clinical Trials
In the Phase 2 clinical trial of teprotumumab, researchers randomly assigned 42 patients to teprotumumab and 45 to placebo. In phase 3, they randomly assigned 41 patients to teprotumumab and 42 to placebo.
Results showed that at 24 weeks, proptosis improved by 2 mm or more in 20% of patients assigned to teprotumumab and 9.5% of those assigned to placebo. At the same time, proptosis decreased by 2.95 mm and 3.32 mm, respectively, in patients included in phase 2 and phase 3 trials.
Other benefits included a grade 1 improvement in diplopia, an improved quality of life score, and a final clinical activity score of 0 or 1. Adverse events included inflammatory bowel disease, diarrhea, hyperglycemia, spasms muscle aches, mild nausea, and infusion reaction.
The ability to treat patients with ASD and achieve better outcomes has been improved with the availability of teprotumumab.
Shriver, who also holds the Jim O’Brien Gross and Donnita Gross Chair in Ophthalmology at Iowa Carver, related the case of a 73-year-old woman who had suffered from PDD for almost 3 decades and suffered a plethora of treatments.
At last visit, she presented with new-onset binocular diplopia and orbital pain. Shriver started the treatment regimen with prednisone for 3 days to check for inflammation, to which the patient responded positively. Shriver continued treatment with 8 infusions of teprotumumab; adverse effects included diarrhea and gastrointestinal upset, tinnitus, and decreased hearing.
The proptosis decreased by 3 mm in the right eye and by 4 mm in the left eye. Left eye motility decreased from -2 to -1 supraduction. The patient had a sustained response 6 months after treatment ended, according to Shriver.
Three of his other patients who were also treated for PDD with teprotumumab experienced a reduction in proptosis of 2.5 to 4.5 mm.
Steps for ophthalmologists
Shriver outlined some practical steps ophthalmologists should follow in the clinic for their patients with ASD.
She recommended that they keep TED in mind and get thyroid dysfunction under control. They should also educate patients on the importance of quitting smoking and adopting a healthy lifestyle that includes taking a selenium supplement or consuming Brazil nuts and vitamin D supplementation. , she emphasized the importance of patient education; patients can receive unbiased information about TED in patient tutorials, such as those available at EyeRounds.org.
If ophthalmologists suspect PDD, they should refer or treat patients as soon as possible since insurance company criteria vary. For example, some companies stipulate that to be covered, patients cannot have Graves’ disease for 9 months.
Shriver also mentioned that while traditional therapies play a role in treatment, patients have the opportunity to benefit from newer treatments and trials.
The future of TED
Shriver said she sees the present as a very exciting time in TED with the advent of better treatments. Previously, progress in the treatment of the disease was very slow compared to the progress of various diseases in other ophthalmic subspecialties.
However, many questions around TED remain to be resolved. These include who will benefit from the therapy, whether they are patients with chronic conditions or those with low clinical activity scores; how many doses are needed; who is at risk for rebound and adverse events; and how to control costs.
Shriver also highlighted the need for investigator-initiated trials with critical analysis of results, head-to-head trials and the involvement of international colleagues to include more diverse patient populations.
“Other drugs are currently in the pipeline,” Shriver concluded. “The next few years should prove to be a very exciting time for ASD patients and the doctors who treat them.”
Erin Shriver, MD
Email: [email protected]
This article is adapted from Shriver’s presentation at the Real World Ophthalmology Virtual Meeting. She is an advisor and consultant for Horizon Therapeutics.