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)
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四川大学华西医院[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
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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外文
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出版当年[2024]版:
无
最新[2023]版:
大类|4 区医学
小类|4 区内分泌学与代谢
第一作者:
第一作者机构:[1]Omi Medical Center, Kusatsu 525-8585, Japan[*1]Omi Medical Center, 1660 Yabase, Kusatsu 525-8585, Japan
通讯作者:
通讯机构:[1]Omi Medical Center, Kusatsu 525-8585, Japan[*1]Omi Medical Center, 1660 Yabase, Kusatsu 525-8585, Japan
推荐引用方式(GB/T 7714):
Shimatsu Akira,Biller Beverly Mk,Fleseriu Maria,et al.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)[J].Endocrine Journal.2024,doi:10.1507/endocrj.EJ24-0153.
APA:
Shimatsu Akira,Biller Beverly Mk,Fleseriu Maria,Pivonello Rosario,Lee Eun Jig...&Snyder Peter J.(2024).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).Endocrine Journal,,
MLA:
Shimatsu Akira,et al."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)".Endocrine Journal .(2024)