Long-term outcomes of osilodrostat in Cushing's disease: LINC 3 study extension.

Autor:	Fleseriu M; Pituitary Center, Departments of Medicine and Neurological Surgery, Oregon Health & Science University, Portland, Oregon, USA., Newell-Price J; Department of Oncology and Metabolism, The Medical School, University of Sheffield, Sheffield, UK., Pivonello R; Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Naples, Italy., Shimatsu A; Advanced Medical Care Center, Omi Medical Center, Kusatsu, Japan., Auchus RJ; Division of Metabolism, Endocrinology and Diabetes, Departments of Internal Medicine and Pharmacology, University of Michigan, Ann Arbor, Michigan, USA., Scaroni C; Endocrinology Unit, Department of Medicine, University Hospital, Padova, Italy., Belaya Z; Department of Neuroendocrinology and Bone Disease, Endocrinology Research Centre, Moscow, Russia., Feelders RA; Department of Internal Medicine, Endocrine Section, Erasmus Medical Center, Rotterdam, The Netherlands., Vila G; Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria., Houde G; Division of Endocrinology, Department of Medicine, University of Sherbrooke, Sherbrooke, Canada., Walia R; Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India., Izquierdo M; Novartis Pharma AG, Basel, Switzerland., Roughton M; Novartis Pharma AG, Basel, Switzerland., Pedroncelli AM; Recordati AG, Basel, Switzerland., Biller BMK; Neuroendocrine and Pituitary Tumor Clinical Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Jazyk:	angličtina
Zdroj:	European journal of endocrinology [Eur J Endocrinol] 2022 Sep 16; Vol. 187 (4), pp. 531-541. Date of Electronic Publication: 2022 Sep 16 (Print Publication: 2022).
DOI:	10.1530/EJE-22-0317
Abstrakt:	Objective: To investigate the long-term efficacy and tolerability of osilodrostat, a potent oral 11β-hydroxylase inhibitor, for treating Cushing's disease (CD). Design/methods: A total of 137 adults with CD and mean 24-h urinary free cortisol (mUFC) > 1.5 × upper limit of normal (ULN) received osilodrostat (starting dose 2 mg bid; maximum 30 mg bid) during the prospective, Phase III, 48-week LINC 3 (NCT02180217) core study. Patients benefiting from osilodrostat at week 48 could enter the optional extension (ending when all patients had received ≥ 72 weeks of treatment or discontinued). Efficacy and safety were assessed for all enrolled patients from the core study baseline. Results: Median osilodrostat exposure from the core study baseline to study end was 130 weeks (range 1-245) and median average dose was 7.4 mg/day (range 0.8-46.6). The reduction in mean mUFC achieved during the core was maintained during the extension and remained ≤ ULN. Of 106 patients, 86 (81%) patients who entered the extension had mUFC ≤ ULN at week 72. Improvements in cardiovascular/metabolic-related parameters, physical manifestations of hypercortisolism (fat pads, central obesity, rubor, striae, and hirsutism in females), and quality of life in the core study were also maintained or improved further during the extension. No new safety signals were reported; 15/137 (10.9%) and 12/106 (11.3%) patients discontinued for adverse events during the core and extension, respectively. Mean testosterone in females decreased towards baseline levels during the extension. Conclusions: Data from this large, multicentre trial show that long-term treatment with osilodrostat sustains cortisol normalisation alongside clinical benefits in most patients with CD and is well tolerated.
Databáze:	MEDLINE
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