{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T01:44:01Z","timestamp":1794361441704,"version":"4.9.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008792","name":"Novartis Pharma","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":[[2025,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Evaluate how osilodrostat dose and baseline mean urinary free cortisol (mUFC) affect treatment outcomes and provide evidence-based guidance on personalized medical treatment for patients with Cushing's disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods\/design<\/jats:title>\n                    <jats:p>Individual-patient data from the Phase II LINC 2 and Phase III LINC 3 and LINC 4 core and extension periods were pooled, excluding periods when patients received placebo (LINC 3 and LINC 4). Outcomes were evaluated in patients with available data across common time points.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Two hundred and twenty-nine patients were treated: starting osilodrostat dose 2\u2005mg twice daily, median average dose per patient 6.8\u2005mg\/day for a mean of 113.7 weeks (standard deviation 73.1). mUFC control (not exceeding the upper limit of normal) was achieved within 4-12 weeks in most patients and sustained throughout. Median time to first mUFC control was 35 days, longer with increasing baseline mUFC. Most common dose for first mUFC control was 4\u2005mg\/day (33.2% of patients; median dose 10\u2005mg\/day [range 2-60]). Adverse events (AEs) generally occurred more often during dose titration (baseline to week 12) than long-term treatment (week &amp;gt;12), but could occur at any time. AEs were manageable in most patients; n = 37 (16.2%) discontinued because of AEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this analysis of the largest and longest prospective interventional studies of an adrenal steroidogenesis inhibitor to date, osilodrostat provided rapid and sustained mUFC control, with dose decreases possible over the long term. AE frequency generally decreased over time, with no relationship with osilodrostat dose. Personalized adjustment of osilodrostat dose is important to optimize outcomes for patients with Cushing's disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration numbers<\/jats:title>\n                    <jats:p>LINC 2 (NCT01331239); LINC 3 (NCT02180217); and LINC 4 (NCT02697734).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvaf207","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T11:53:09Z","timestamp":1759492389000},"page":"506-517","source":"Crossref","is-referenced-by-count":11,"title":["Osilodrostat dose impact on efficacy\/safety in Cushing's disease: large, pooled analysis of LINC 2, 3, and 4"],"prefix":"10.1093","volume":"193","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9284-6289","authenticated-orcid":false,"given":"Maria","family":"Fleseriu","sequence":"first","affiliation":[{"name":"Departments of Medicine and Neurological Surgery, Pituitary Center, Oregon Health & Science University , Portland, OR 97239 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9632-1348","authenticated-orcid":false,"given":"Rosario","family":"Pivonello","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Universit\u00e0 Federico II di Napoli , 80131 Naples ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Lacroix","sequence":"additional","affiliation":[{"name":"D\u00e9partement de M\u00e9decine, Service d'Endocrinologie et Centre de Recherche du CHUM, Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM) , Montreal, H2X 0C1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly M K","family":"Biller","sequence":"additional","affiliation":[{"name":"Neuroendocrine Clinical and Pituitary Tumor Clinical Center, Massachusetts General Hospital , Boston, MA 02114 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2319-391X","authenticated-orcid":false,"given":"Richard","family":"Feelders","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Endocrine Section, Erasmus Medical Center , 3015 GD Rotterdam ,","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f4nica","family":"Gadelha","sequence":"additional","affiliation":[{"name":"Neuroendocrinology Research Center, Endocrinology Section, Medical School and Hospital Universit\u00e1rio Clementino Fraga Filho, Universidade Federal do Rio de Janeiro , Rio de Janeiro, 21941-913 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2551-3008","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Bertherat","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Centre de R\u00e9f\u00e9rence des Maladies Rares de la Surr\u00e9nale, H\u00f4pital Cochin, AP-HP, and Universit\u00e9 de Paris Cit\u00e9 , F-75014, Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanna","family":"Belaya","sequence":"additional","affiliation":[{"name":"Department of Neuroendocrinology and Bone Disease, Endocrinology Research Centre , Moscow 117292 ,","place":["Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Piacentini","sequence":"additional","affiliation":[{"name":"Recordati SpA , Milan 20148 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto 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