{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:44:54Z","timestamp":1790304294417,"version":"4.1.0"},"reference-count":40,"publisher":"The Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008792","name":"Novartis Pharma AG","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008792","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Interleukin (IL)-17, a key proinflammatory cytokine, drives inflammation and fibrosis in Graves orbitopathy (GO), and elevated IL-17 and Th17 cells correlate with disease activity and severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The ORBIT study aimed to evaluate the efficacy and safety of secukinumab, an IL-17A inhibitor, in individuals with active, moderate-to-severe GO.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A randomized, double-blind, placebo-controlled, parallel-group, multicenter trial was conducted. Adults with active, moderate-to-severe, non-sight\u2013threatening GO randomly (1:1) received secukinumab 300\u2005mg or placebo subcutaneously over a 16-week double-blind treatment period, followed by an additional 16-week open-label treatment phase for proptosis nonresponders. Safety parameters, thyroid-related hormones, and autoantibodies were also assessed. The primary end point was overall response of reduced Clinical Activity Score (CAS) of 2 or more points and a reduction of 2\u2005mm or greater in proptosis from baseline without worsening in the fellow eye at week 16.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-eight adult GO patients with a CAS of 4 or greater were enrolled (secukinumab, n = 14; placebo, n = 14). None in either the secukinumab or placebo group achieved an overall response at weeks 16 and 32, respectively, when all patients received open-label secukinumab. No clinically meaningful changes were observed in ophthalmic symptoms and signs, proptosis, lid aperture, eye muscle motility, CAS, and health-related quality of life either at week 16 or week 32. No meaningful effect on serum levels of thyroid-related hormones and antibodies was observed. Secukinumab was well tolerated, with mostly mild adverse events. Neither treatment-induced study discontinuation nor new safety signals were registered.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Secukinumab did not show clinical efficacy vs placebo when treating patients with active, moderate-to-severe GO.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf655","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T12:30:57Z","timestamp":1765197057000},"page":"1248-1257","source":"Crossref","is-referenced-by-count":3,"title":["Secukinumab in Moderate-to-Severe Graves Orbitopathy: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study"],"prefix":"10.1210","volume":"111","author":[{"given":"Jan","family":"Wolf","sequence":"first","affiliation":[{"name":"Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center , Mainz 55101 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