Division of Clinical Sciences, Marian University College of Osteopathic Medicine, Indianapolis, IN, USA.
Expert Opin Pharmacother. 2021 Jun;22(9):1099-1106. doi: 10.1080/14656566.2021.1897106. Epub 2021 Mar 11.
The treatment of Cushing's disease (CD) has been advanced well with the introduction of treatment options like transsphenoidal surgery, radiosurgery, bilateral adrenalectomy, and various classes of medication; however, many patients still fail to achieve disease remission. Osilodrostat, an orally bioavailable adrenal steroidogenesis inhibitor, was approved in the USA and EU in 2020 for the treatment of CD.
This review provides an overview of Cushing's disease and the newly FDA approved 11β-hydroxylase inhibitor, osilodrostat, for CD with a focus on pharmacodynamics, pharmacokinetics, safety and efficacy data, and phase 2 and 3 clinical trials.
Osilodrostat has proven clinical efficacy and tolerability in phase 2 and 3 trials with CD patients who had an inadequate or reoccurring response to transsphenoidal surgery (TSS) and conventional first-line treatment. The phase 3 trial (LINC3) had 86% of the treatment group respond with normal urinary free cortisol (UFC) level compared to 29% in the placebo group ( < 0.001). Deemed as well-tolerated in all current pivotal trials, oral osilodrostat provides a noninvasive option for patients who cannot undergo surgery or patients who have reoccurring hypercortisolemia.
随着治疗选择（如经蝶窦手术、放射外科、双侧肾上腺切除术和各种类别的药物）的引入，库欣病（CD）的治疗已经取得了很大进展；然而，许多患者仍未达到疾病缓解。口服生物利用度的肾上腺类固醇生成抑制剂奥昔罗司他于 2020 年在美国和欧盟获批用于治疗 CD。
本文综述了库欣病以及新获得美国食品药品监督管理局批准的 11β-羟化酶抑制剂奥昔罗司他治疗 CD 的情况，重点介绍了药效学、药代动力学、安全性和疗效数据，以及 2 期和 3 期临床试验。
奥昔罗司他在 2 期和 3 期临床试验中对经蝶窦手术（TSS）和常规一线治疗无效或复发的 CD 患者具有临床疗效和耐受性。3 期试验（LINC3）中，治疗组有 86%的患者尿游离皮质醇（UFC）水平正常，而安慰剂组为 29%（<0.001）。在所有当前的关键试验中，口服奥昔罗司他被认为具有良好的耐受性，为不能手术或反复出现皮质醇增多症的患者提供了一种非侵入性的选择。
