{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:55:47Z","timestamp":1791932147654,"version":"4.3.4"},"reference-count":31,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019637","name":"Horizon Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019637","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,21]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Context<\/jats:title><jats:p>Early inflammatory thyroid eye disease (TED) can lead to symptomatic chronic disease, including disabling proptosis. Teprotumumab, an insulin-like growth factor-1 receptor (IGF-1R) inhibitor, previously demonstrated efficacy in acute, high-inflammation TED trials.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We present data from the first placebo-controlled trial with teprotumumab in chronic\/low disease activity TED.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This randomized double-masked, placebo-controlled trial, conducted at 11 US centers, enrolled adult participants with TED duration of 2 to 10 years, Clinical Activity Score (CAS) \u2264 1 or no additional inflammation or progression in proptosis\/diplopia for \u22651 year, proptosis \u22653 mm from before TED and\/or from normal, euthyroid\/mildly hypo\/hyperthyroid, no prior teprotumumab, and no steroids within 3 weeks of baseline. Patients received (2:1) intravenous teprotumumab or placebo once every 3 weeks (total 8 infusions). The primary endpoint was proptosis (mm) improvement at Week 24. Adverse events (AEs) were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 62 (42 teprotumumab and 20 placebo) patients were randomized. At Week 24, least squares mean (SE) proptosis improvement was greater with teprotumumab (\u22122.41 [0.228]) than with placebo (\u22120.92 [0.323]), difference \u22121.48 (95% CI \u22122.28, \u22120.69; P = .0004). Proportions of patients with AEs were similar between groups. Hyperglycemia was reported in 6 (15%) vs 2 (10%) and hearing impairment in 9 (22%) vs 2 (10%) with teprotumumab and placebo, respectively. AEs led to discontinuation in 1 teprotumumab (left ear conductive hearing loss with congenital anomaly) and 1 placebo patient (infusion-related). There were no deaths.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Teprotumumab significantly improved proptosis vs placebo in longstanding\/low inflammation TED, demonstrating efficacy regardless of disease duration\/activity. The safety profile was comparable to that previously reported.<\/jats:p><\/jats:sec>","DOI":"10.1210\/clinem\/dgad637","type":"journal-article","created":{"date-parts":[[2023,11,5]],"date-time":"2023-11-05T15:04:46Z","timestamp":1699196686000},"page":"25-35","source":"Crossref","is-referenced-by-count":94,"title":["Efficacy and Safety of Teprotumumab in Patients With Thyroid Eye Disease of Long Duration and Low Disease Activity"],"prefix":"10.1210","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3435-8161","authenticated-orcid":false,"given":"Raymond S","family":"Douglas","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Cedars Sinai Medical Center , Los Angeles, CA 90048 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Couch","sequence":"additional","affiliation":[{"name":"John F. Hardesty MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine , St Louis, MO 63130 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara T","family":"Wester","sequence":"additional","affiliation":[{"name":"Bascom Palmer Eye Institute, University of Miami , Miami, FL 33136 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian T","family":"Fowler","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The University of Tennessee Health Science Center, Hamilton Eye Institute , Memphis, TN 38163 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine Y","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shiley Eye Institute, University of California San Diego , La Jolla, CA 92037 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prem S","family":"Subramanian","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology, Neurology, and Neurosurgery, UC Health Sue Anschutz-Rodgers Eye Center, University of Colorado School of Medicine , Aurora, CO 80045 , USA"},{"name":"Department of Surgery, Division of Ophthalmology, Uniformed Services University of the Health Sciences , Bethesda, MD 20814 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Tang","sequence":"additional","affiliation":[{"name":"Eye Wellness Center, Neuro-Eye Clinical Trials, Inc. , Houston, TX 77074 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quang T","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Touro University , Henderson, NV 89014 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robi N","family":"Maamari","sequence":"additional","affiliation":[{"name":"John F. Hardesty MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine , St Louis, MO 63130 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoaib","family":"Ugradar","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Cedars Sinai Medical Center , Los Angeles, CA 90048 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Hsu","sequence":"additional","affiliation":[{"name":"Clinical Development, Horizon Therapeutics plc , Deerfield, IL 60015 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6845-8152","authenticated-orcid":false,"given":"Michael","family":"Karon","sequence":"additional","affiliation":[{"name":"Clinical Development, Horizon Therapeutics plc , Deerfield, IL 60015 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius N","family":"Stan","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic , Rochester, MN 55905 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2023,10,31]]},"reference":[{"issue":"2","key":"2023122122192809900_dgad637-B1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1001\/jamaophthalmol.2022.3225","article-title":"Utility assessment of moderate to severe thyroid eye disease health states","volume":"141","author":"Smith","year":"2023","journal-title":"JAMA Ophthalmol"},{"issue":"4","key":"2023122122192809900_dgad637-B2","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1007\/s40123-021-00385-8","article-title":"Quality of life in patients with chronic thyroid eye disease in the United States","volume":"10","author":"Cockerham","year":"2021","journal-title":"Ophthalmol Ther"},{"issue":"9","key":"2023122122192809900_dgad637-B3","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.eprac.2022.06.003","article-title":"Inflammatory and noninflammatory thyroid eye disease: comparison of disease signs, symptoms, and quality of life in patients in the United States","volume":"28","author":"Wang","year":"2022","journal-title":"Endocr Pract"},{"key":"2023122122192809900_dgad637-B4","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.2147\/TCRM.S193018","article-title":"Thyroid eye disease: how a novel therapy may change the treatment paradigm","volume":"15","author":"Wang","year":"2019","journal-title":"Ther Clin Risk Manag"},{"issue":"5","key":"2023122122192809900_dgad637-B5","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1159\/000477803","article-title":"Does Graves\u2019 orbitopathy ever disappear? 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