Fleseriu Maria, Auchus Richard J, Huang Wenyu, Spencer-Segal Joanna L, Yuen Kevin C J, Dacus Kelley C, Padgett Julianne, Babler Elizabeth K, Das Ashis K, Campos Cynthia, Broder Michael S, Ioachimescu Adriana G
Departments of Medicine and Neurological Surgery, Pituitary Center, Oregon Health & Science University, Portland, OR 97239, USA.
Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI 48109, USA.
J Endocr Soc. 2025 Mar 15;9(5):bvaf046. doi: 10.1210/jendso/bvaf046. eCollection 2025 May.
In clinical trials, osilodrostat (11β-hydroxylase inhibitor) effectively reduced cortisol levels in patients with endogenous Cushing syndrome (CS).
A real-world study (ILLUSTRATE) was conducted evaluating osilodrostat use in patients with various etiologies of CS in the United States.
A retrospective chart-review study was conducted of adults with CS treated with osilodrostat between May 1, 2020, and October 29, 2021.
A total of 42 patients (Cushing disease, n = 34; CS due to adrenal adenoma, n = 5; ectopic adrenocorticotropin syndrome [EAS], n = 3) were included. Starting doses were 2 mg twice daily in 27/42 patients (64.3%), maintenance doses were 2 mg twice daily in 6 of 9 patients (66.7%) attaining them. During osilodrostat treatment, urinary free cortisol (UFC) decreased below the upper limit of normal (ULN) in 14 of 20 patients (70.0%) with pretreatment UFC greater than the ULN. Osilodrostat response was observed across a range of doses (2-20 mg/day). In Cushing disease, median UFC and late-night salivary cortisol decreased from 3.03 and 2.39 × ULN, respectively, to 0.71 and 1.13 × ULN at last assessment in those with available data (n = 17 and 8, respectively). UFC decreased in all patients with adrenal CS or EAS with available data (n = 2 each). There were no unexpected safety signals; the most common adverse events (incidence ≥20%) were fatigue, nausea, and lower-extremity edema. Glucocorticoid withdrawal syndrome and/or adrenal insufficiency were reported in 12 of 42 patients (28.6%) after osilodrostat initiation, resulting in treatment discontinuation in 4.
In routine practice with dosing individualized according to clinical condition, response, and tolerability, osilodrostat was effective and well tolerated regardless of CS etiology and severity.
在临床试验中，奥西卓司他（11β-羟化酶抑制剂）可有效降低内源性库欣综合征（CS）患者的皮质醇水平。
开展一项真实世界研究（ILLUSTRATE），评估美国不同病因的CS患者使用奥西卓司他的情况。
对2020年5月1日至2021年10月29日期间接受奥西卓司他治疗的成年CS患者进行回顾性病历审查研究。
共纳入42例患者（库欣病，n = 34；肾上腺腺瘤所致CS，n = 5；异位促肾上腺皮质激素综合征[EAS]，n = 3）。42例患者中有27例（64.3%）起始剂量为每日两次，每次2mg；9例达到维持剂量的患者中有6例（66.7%）维持剂量为每日两次，每次2mg。在奥西卓司他治疗期间，20例治疗前尿游离皮质醇（UFC）高于正常上限（ULN）的患者中有14例（70.0%）UFC降至ULN以下。在2-20mg/天的一系列剂量中均观察到奥西卓司他的反应。在库欣病患者中，有可用数据的患者（分别为n = 17和8）在最后一次评估时，UFC中位数和午夜唾液皮质醇分别从3.03和2.39×ULN降至0.71和1.13×ULN。所有有可用数据的肾上腺CS或EAS患者（各n = 2）的UFC均下降。未发现意外的安全信号；最常见的不良事件（发生率≥20%）为疲劳、恶心和下肢水肿。42例患者中有12例（28.6%）在开始使用奥西卓司他后出现糖皮质激素戒断综合征和/或肾上腺功能不全，4例因此停药。
在根据临床情况、反应和耐受性进行个体化给药的常规实践中，无论CS的病因和严重程度如何，奥西卓司他均有效且耐受性良好。
