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Osilodrostat treatment in patients with Cushing's disease of Asian or non-Asian origin: a pooled analysis of two Phase III randomized trials (LINC 3 and LINC 4)

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机构: [1]Omi Medical Center, Kusatsu 525-8585, Japan [2]Neuroendocrine and Pituitary Tumor Clinical Center, Massachusetts General Hospital, Boston, MA 02114, USA [3]Pituitary Center, Departments of Medicine and Neurological Surgery, Oregon Health & Science University, Portland, OR 97239,USA [4]Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Naples 80131, Italy [5]Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, South Korea [6]Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand [7]Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, South Korea [8]Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India [9]Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China [10]Division of Endocrinology, Sun Yat-sen University, Guangzhou 510275, China [11]Recordati SpA, Milan 20148, Italy [12]Recordati AG, Basel 4057, Switzerland [13]Camurus AB, Lund 223 62, Sweden [14]Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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关键词: Cushing’s syndrome Clinical trial Efficacy Safety Race

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Cushing's disease is associated with increased morbidity and mortality. Osilodrostat, a potent oral 11β-hydroxylase inhibitor, provided rapid, sustained mean urinary free cortisol (mUFC) normalization in Cushing's disease patients in two Phase III studies (LINC 3, NCT02180217; LINC 4, NCT02697734). Here, we evaluate the efficacy and safety of osilodrostat in Cushing's disease in patients of Asian origin compared with patients of non-Asian origin. Pooled data from LINC 3 and LINC 4 were analyzed. Outcomes were evaluated separately for Asian and non-Asian patients. For the analysis, 210 patients were included; 56 (27%) were of Asian origin. Median (minimum-maximum) osilodrostat dose was 3.8 (1-25) and 7.3 (1-47) mg/day in Asian and non-Asian patients, respectively. mUFC control was achieved at weeks 48 and 72 in 64.3% and 68.1% of Asian and 68.2% and 75.8% of non-Asian patients. Improvements in cardiovascular and metabolic-related parameters, physical manifestations of hypercortisolism, and quality of life were similar in both groups. Most common adverse events (AEs) were adrenal insufficiency (44.6%) in Asian and nausea (45.5%) in non-Asian patients. AEs related to hypocortisolism and pituitary tumor enlargement occurred in more Asian (58.9% and 21.4%) than non-Asian patients (40.3% and 9.1%). Of Asian and non-Asian patients, 23.2% and 13.6%, respectively, discontinued because of AEs. Asian patients with Cushing's disease generally required numerically lower osilodrostat doses than non-Asian patients to achieve beneficial effects. Hypocortisolism-related AEs were reported in more Asian than non-Asian patients. Together, these findings suggest that Asian patients are more sensitive to osilodrostat than non-Asian patients.

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大类 | 4 区 医学
小类 | 4 区 内分泌学与代谢
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第一作者机构: [1]Omi Medical Center, Kusatsu 525-8585, Japan [*1]Omi Medical Center, 1660 Yabase, Kusatsu 525-8585, Japan
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通讯机构: [1]Omi Medical Center, Kusatsu 525-8585, Japan [*1]Omi Medical Center, 1660 Yabase, Kusatsu 525-8585, Japan
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