The Efficacy of Teprotumumab for Chronic, Progressive Thyroid Eye Disease Greater Than 9 Months

Abstract Purpose: To evaluate the efficacy of teprotumumab for the treatment of patients with chronic, progressive Thyroid Eye Disease (TED) who do not meet the inclusion and exclusion criteria used in prior clinical trials. Methods: This is a prospective case series of patients with chronic, progressive TED, defined as ocular symptoms of more than 9 months prior to treatment initiation with teprotumumab, an insulin-like growth factor I receptor inhibitor (10 mg/kg for the first infusion then 20 mg/kg for subsequent infusions, every three weeks for a total 8 infusions). This study included patients with a Clinical Activity Score (CAS) greater than or equal to 4. Data collected included patients’ age, sex, race, baseline thyroid status, thyroid stimulating immunoglobulin, CAS, smoking status, best corrected visual acuity, intraocular pressure, Schirmer’s, pupil exam, extraocular motility, Gorman diplopia score, and exophthalmometer measurements. Pre-infusion and post-infusion external photos in all 9 gazes, orbital imaging (CT or MRI), Humphrey visual fields and optical coherence tomography were obtained when possible. Results: Ten patients with chronic TED were treated with teprotumumab either as a primary treatment or following other interventions including oral prednisone, intravenous methylprednisolone, orbital radiation, orbital decompression and/or eyelid surgery. The age range was 55 to 79, with 5 female patients and 5 male patients. Four of the patients were African American and 6 of the patients were White/Non-Hispanic. The number of years the patients had been diagnosed with Graves’ disease ranged from 4 to 33 years, with ocular involvement spanning 4 to 15 years. Patients had CT scans of the orbits to document muscle size prior to initiation, and external photos were taken at each visit. All patients improved subjectively after the first infusion and objectively by the fourth infusion. We will report the long-term follow-up after 8 infusions at ENDO2021. Discussion: Teprotumumab is a fully human monoclonal IgG1 antibody that blocks the IGF-1 receptor, disrupting the cell-to-cell signaling of the immunologic cascade and is independent of the duration or severity of TED. At this time, FDA approval for teprotumumab is for the treatment of TED without any specific restrictions. However, our teprotumumab-treated patients included those who would have been excluded in the phase 2 and 3 clinical trials due to: (1) poor thyroid control, (2) previous orbital surgery, (3) previous therapeutic interventions including steroids and radiation, (4) visual loss due to compressive optic neuropathy or exposure keratopathy and (5) chronic TED greater than 9 months. In our series, we found that teprotumumab was as effective in a wider population of chronic TED patients than included in the clinical trials.