LBSAT238 Teprotumumab Reduces Orbital Fat And Muscle Volume In Patients With Thyroid Eye Disease

Teprotumumab, a novel IGF-1R antibody has been shown to reduce proptosis in patients with thyroid eye disease (TED) in 2 randomized controlled trials. At present, it is unclear whether the reduction in proptosis is related to a decrease in extraocular muscle or orbital fat tissue. In this prospective longitudinal study, we reviewed the changes to orbital fat and muscle, and compared them, in consecutive patients with TED, who had completed treatment with teprotumumab (8 infusions). The primary outcome was change in orbital fat and muscle volume within 6 weeks of starting and completing therapy. Secondary outcome measures included change in proptosis and the clinical activity score (CAS). All patients had either CT or MRI with ≤ 1 mm slice thickness. Three-dimensional volumetric analysis of the orbital fat and muscle volume was performed using the previously validated 3D image analysis software, MIMICS (Materialise, Leuven, Belgium). Hounsfield units of fat and muscle were defined manually. All extraocular muscle tissue and fat between the orbital septum (eyelid) and the orbital outlet of the optic canal was included. A 3D model created by voxel addition was expressed in millimeters cubed. Segmentation and measurements were performed independently by two graders to review repeatability and observer variability. In line with previous clinical trials, the orbit with the most proptosis was defined as the study orbit and the contralateral orbit was designated the fellow orbit. Twenty-one patients (15 females and 6 males) met the inclusion criteria. Mean (SD) age was 55 (16), while mean (SD) duration of TED was 71 (46) months. There was a reduction of 3 mm in both; study and fellow orbits following treatment (p < 0. 01 for both). Compared to baseline, there was a mean (SD) CAS reduction of 4 (1) in the study orbit and 2.4 (1.1) in the fellow orbit (p < 0. 01 for both). Following therapy, mean (SD) reduction in muscle tissue was 1691 mm3 (1358) in the study orbit and 1714 mm3 (1927) in the fellow orbit (p < 0. 01 when compared to baseline for each). The mean (SD) reduction of fat volume was 1382 mm3 (1318) in the study orbit and 933 mm3 (1699) in the fellow orbit (p < 0. 01 when compared to baseline for each). There was no difference between fat and muscle reduction for the study orbit (p = 0.4) or fellow orbit (p = 0.2). There was a significant correlation between a reduction in proptosis and reduction in orbital soft tissue (fat and muscle) volume. The results of this study suggest that following treatment with teprotumumab, there is a significant decrease in orbital fat and muscle volume. This reduction in soft tissue volume likely drives the reduction in proptosis. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.