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)
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)....
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The Japan Endocrine Society
2024-12-01
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| Series: | Endocrine Journal |
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| Online Access: | https://www.jstage.jst.go.jp/article/endocrj/71/12/71_EJ24-0153/_html/-char/en |
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| author | Akira Shimatsu Beverly MK Biller Maria Fleseriu Rosario Pivonello Eun Jig Lee Rattana Leelawattana Jung Hee Kim Rama Walia Yerong Yu Zhihong Liao Andrea Piacentini Alberto M Pedroncelli Peter J Snyder |
| author_facet | Akira Shimatsu Beverly MK Biller Maria Fleseriu Rosario Pivonello Eun Jig Lee Rattana Leelawattana Jung Hee Kim Rama Walia Yerong Yu Zhihong Liao Andrea Piacentini Alberto M Pedroncelli Peter J Snyder |
| author_sort | Akira Shimatsu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-84a2c66b16f74d00920be9d203bbcd98 |
| institution | Kabale University |
| issn | 1348-4540 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | The Japan Endocrine Society |
| record_format | Article |
| series | Endocrine Journal |
| spelling | doaj-art-84a2c66b16f74d00920be9d203bbcd982025-01-22T05:34:07ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402024-12-0171121103112310.1507/endocrj.EJ24-0153endocrjOsilodrostat 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)Akira Shimatsu0Beverly MK Biller1Maria Fleseriu2Rosario Pivonello3Eun Jig Lee4Rattana Leelawattana5Jung Hee Kim6Rama Walia7Yerong Yu8Zhihong Liao9Andrea Piacentini10Alberto M Pedroncelli11Peter J Snyder12Omi Medical Center, Kusatsu 525-8585, JapanNeuroendocrine and Pituitary Tumor Clinical Center, Massachusetts General Hospital, Boston, MA 02114, USAPituitary Center, Departments of Medicine and Neurological Surgery, Oregon Health & Science University, Portland, OR 97239, USADipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Naples 80131, ItalyDepartment of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, South KoreaDivision of Endocrinology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, ThailandDepartment of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, South KoreaDepartment of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, IndiaDepartment of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, ChinaDivision of Endocrinology, Sun Yat-sen University, Guangzhou 510275, ChinaRecordati SpA, Milan 20148, ItalyRecordati AG, Basel 4057, SwitzerlandPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USACushing’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.https://www.jstage.jst.go.jp/article/endocrj/71/12/71_EJ24-0153/_html/-char/encushing’s syndromeclinical trialefficacysafetyrace |
| spellingShingle | Akira Shimatsu Beverly MK Biller Maria Fleseriu Rosario Pivonello Eun Jig Lee Rattana Leelawattana Jung Hee Kim Rama Walia Yerong Yu Zhihong Liao Andrea Piacentini Alberto M Pedroncelli Peter J Snyder 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 cushing’s syndrome clinical trial efficacy safety race |
| title | 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) |
| title_full | 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) |
| title_fullStr | 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) |
| title_full_unstemmed | 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) |
| title_short | 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) |
| title_sort | 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 |
| topic | cushing’s syndrome clinical trial efficacy safety race |
| url | https://www.jstage.jst.go.jp/article/endocrj/71/12/71_EJ24-0153/_html/-char/en |
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