Teprotumumab Effects on Thyroid Eye Disease in a Prospective Japanese Cohort: MRI-Based Comparison with Intravenous Glucocorticoid Therapy

Context. Teprotumumab (TEP) is an emerging treatment for thyroid eye disease (TED), but real-world evidence outside the United States remains limited, and detailed changes in orbital components have not been fully clarified. Objective. To evaluate the effectiveness of TEP based on clinical manifestations and magnetic resonance imaging (MRI) findings, and compare it with that of intravenous glucocorticoid (IVGC) therapy. Methods: The TEP cohort included all 18 patients who started TEP therapy at Kyoto University Hospital by July 31, 2025. A historical IVGC cohort included 20 patients matched to the TEP cohort. Results: During 24 weeks of TEP therapy, proptosis measured using a Hertel exophthalmometer improved from 22 (20-22) to 19 (16-21) mm (p = 0.025), and clinical activity score decreased from 4 (3-5) to 1 (0-1) point (p < 0.001). Among 15 patients with diplopia, a reduction of at least 1 point in Gorman score was observed in 9 patients (60.0%). Thyroid-stimulating antibody titers decreased from 1,180% (349-4,710) to 282% (132-504) (p = 0.013). MRI-based comparisons with the IVGC cohort showed that TEP reduced both extraocular muscle and orbital fat areas, whereas IVGC reduced extraocular muscle area but conversely increased orbital fat area. Inflamed extraocular muscles identified on MRI were enlarged at baseline and showed marked shrinkage after both therapies. Conclusion: TEP showed robust effectiveness in Japanese real-world patients with TED. MRI-based analyses revealed distinct effects of TEP and IVGC on orbital fat and identified inflamed extraocular muscles as treatment-responsive components.