Newell-Price John, Fleseriu Maria, Pivonello Rosario, Feelders Richard A, Gadelha Mônica R, Lacroix André, Witek Przemysław, Heaney Anthony P, Piacentini Andrea, Pedroncelli Alberto M, Biller Beverly M K
The School of Medicine and Population Health, University of Sheffield, Sheffield S10 2RX, UK.
Pituitary Center, Departments of Medicine and Neurological Surgery, Oregon Health & Science University, Portland, OR 97239, USA.
J Endocr Soc. 2024 Nov 12;9(1):bvae201. doi: 10.1210/jendso/bvae201. eCollection 2024 Nov 26.
To assess whether simultaneous normalization of late-night salivary cortisol (LNSC) and mean urinary free cortisol (mUFC) in patients with Cushing disease treated with osilodrostat is associated with better clinical outcomes than control of mUFC or LNSC alone.
Pooled data from two phase III osilodrostat studies (LINC 3 and LINC 4) were analyzed. Both comprised a 48-week core phase and an optional open-label extension. Changes in cardiovascular/metabolic-related parameters, physical manifestations of hypercortisolism, and quality of life (QoL) were evaluated across the following patient subgroups: both LNSC and mUFC controlled, only mUFC controlled, only LNSC controlled, and neither controlled.
Of 160 patients included in the analysis, 85.0% had both LNSC and mUFC uncontrolled at baseline. At week 72, 48.6% of patients had both LNSC and mUFC controlled; these patients generally exhibited greater improvements in cardiovascular/metabolic-related parameters than those with only mUFC controlled or both LNSC and mUFC uncontrolled: systolic/diastolic blood pressure, -7.4%/-4.9%, -6.0%/-5.5%, and 2.3%/0.8%, respectively; fasting plasma glucose, -5.0%, -4.8%, and 1.9%; glycated hemoglobin, -5.1%, -4.8%, and -1.3%. Weight, waist circumference, and body mass index improved with control of LNSC and/or mUFC; physical manifestations of hypercortisolism generally improved regardless of LNSC/mUFC control. Patients with both LNSC and mUFC controlled or only mUFC controlled had the greatest improvement from baseline to week 72 in QoL.
In osilodrostat-treated patients with Cushing disease, normalization of LNSC and mUFC led to improvements in long-term outcomes, indicating that treatment should aim for normalization of both parameters for optimal patient outcomes.
NCT02180217 (LINC 3); NCT02697734 (LINC 4).
评估在接受奥西卓司他治疗的库欣病患者中，深夜唾液皮质醇（LNSC）和平均尿游离皮质醇（mUFC）同时恢复正常是否比仅控制mUFC或LNSC能带来更好的临床结局。
对两项III期奥西卓司他研究（LINC 3和LINC 4）的汇总数据进行分析。两项研究均包括一个48周的核心阶段和一个可选的开放标签扩展阶段。在以下患者亚组中评估心血管/代谢相关参数、皮质醇增多症的身体表现和生活质量（QoL）的变化：LNSC和mUFC均得到控制、仅mUFC得到控制、仅LNSC得到控制以及两者均未得到控制。
纳入分析的160例患者中，85.0%在基线时LNSC和mUFC均未得到控制。在第72周时，48.6%的患者LNSC和mUFC均得到控制；这些患者在心血管/代谢相关参数方面的改善通常比仅mUFC得到控制或LNSC和mUFC均未得到控制的患者更大：收缩压/舒张压分别为-7.4%/-4.9%、-6.0%/-5.5%和2.3%/0.8%；空腹血糖分别为-5. 0%、-4.8%和1.9%；糖化血红蛋白分别为-5.1%、-4.8%和-1.3%。体重、腰围和体重指数随着LNSC和/或mUFC的控制而改善；无论LNSC/mUFC是否得到控制，皮质醇增多症的身体表现总体上都有所改善。从基线到第72周，LNSC和mUFC均得到控制或仅mUFC得到控制的患者在生活质量方面的改善最大。
在接受奥西卓司他治疗的库欣病患者中，LNSC和mUFC恢复正常可带来长期结局的改善，这表明治疗应旨在使这两个参数均恢复正常，以实现最佳的患者结局。
NCT02180217（LINC 3）；NCT02697734（LINC 4）。
