New treatment for Graves Opthalmopathy is a game changer and can prevent long standing proptosis and diplopia in patients with Grave disease.
Graves eye disease occurs because of autoimmune development of TSH receptor antibodies and IgF I receptor antibodies binding to both TSH receptor and IGF-1 receptors on orbital fibroblast. These orbital fibroblast then release signals or substances that activate growth of proliferation of orbital tissue, muscles and fat. As a result the eyes can bulge out more (proptosis) and the eye muscles work less well causing double vision (diplopia). When the pressure in the eye increases significantly, as a result of all this eye tissue enlargement, the optic nerve can be squished causing it to atrophy. Then loss of vision occurs. Patients at this late stage may need orbital (eye socket) decompression to save the vision in the eye. there is no grate therapy for this eye disease. steroids are used but without much effectiveness. The cosmetic effects of Graves opthalmopathy on a person\’s appearance are long standing and create long term and affect negatively quality of life.
IGF-I receptors are over-expressed by orbital fibroblasts and by T cells and B cells in persons with Graves’ disease, this is why this is a good therapy trial. Teprotumumab is a monoclonal antibody that blocks IGF-1 receptor binding by these antibodies in orbital tissue. The treatment consist of intravenous infusion given every 3 weeks (total 8 treatment) or 24 weeks. To monitor effectiveness of the drug Clinical score and diplopia (double vision) score was used.
The results are stunning: 73.8% responded with reduction of proptosis versus 13 % in placebo. Actual reduction of proptosis -3.14 millimeters. 60% had suppression of eye disease, and eye muscle mobility in proved in 70 % of people. The before and after pictures were very impressive. Quality of life markedly improved in those patients, and particularly in the sub scale of visual function. Thyroid function was not affected.
Most mild side effects resolved. These are the most common side effects in few patients: nausea, muscle spasm, diarrhea, hyperglycemia in few, mental confusion (1), dysgusia and dry skin. 7 in the trial had significant effects: Hashimots encephalopathy, optic compression requiring surgery detection of infection or colitis.
This very exciting therapy. I don’t know when it will be available in a wider scale. But now you are aware and can pass the word around to all those who need to know and I cannot reach or treat.
This was a featured oral presentation this morning at the American Thyroid Association meeting here in Chicago delivered by Dr. George J. Kahaly, one of the authors of the reference paper I include below. I am fortunate to be here at the ATA meeting this week.
References: Teprotumumab for Thyroid-Associated Ophthalmopathy. Terry J. Smith, M.D., George J. Kahaly, M.D., Ph.D., Daniel G. Ezra, M.D., .et al. N Engl J Med 2017; 376:1748-1761, DOI: 10.1056/NEJMoa1614949