Improved Clinical Outcomes During Long-term Osilodrostat Treatment of Cushing Disease With Normalization of Late-night Salivary Cortisol and Urinary Free Cortisol.

IF 3 Q2 ENDOCRINOLOGY & METABOLISM Journal of the Endocrine Society Pub Date : 2024-11-12 eCollection Date: 2024-11-26 DOI:10.1210/jendso/bvae201

John Newell-Price, Maria Fleseriu, Rosario Pivonello, Richard A Feelders, Mônica R Gadelha, André Lacroix, Przemysław Witek, Anthony P Heaney, Andrea Piacentini, Alberto M Pedroncelli, Beverly M K Biller

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Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Clinical trial identifiers: NCT02180217 (LINC 3); NCT02697734 (LINC 4).

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长期奥西洛他汀治疗库欣病与夜间唾液皮质醇和尿游离皮质醇正常化的改善临床结果

目的：评估接受奥西洛他汀治疗的库欣病患者夜间唾液皮质醇（LNSC）和平均尿游离皮质醇（mUFC）同时正常化是否与单独使用mUFC或LNSC的对照组更好的临床结果相关。方法：对两项III期研究（linc3和linc4）的汇总数据进行分析。两者都包括48周的核心期和可选的开放标签延长期。在以下患者亚组中评估心血管/代谢相关参数的变化、高皮质醇的生理表现和生活质量（QoL）： LNSC和mUFC均控制、仅mUFC控制、仅LNSC控制和均不控制。结果：在纳入分析的160例患者中，85.0%的患者在基线时同时患有LNSC和mUFC。在第72周，48.6%的患者同时控制了LNSC和mUFC；与仅控制mUFC或同时控制LNSC和mUFC的患者相比，这些患者在心血管/代谢相关参数方面通常表现出更大的改善：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，-5.0%,-4.8%和1.9%；糖化血红蛋白，-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控制与否，高皮质醇血症的生理表现普遍改善。从基线到第72周，同时控制LNSC和mUFC或仅控制mUFC的患者的生活质量改善最大。结论：在奥西洛司他治疗的库欣病患者中，LNSC和mUFC的正常化导致了长期预后的改善，表明治疗应以这两个参数的正常化为目标，以获得最佳的患者预后。临床试验标识符：NCT02180217 (LINC 3)；Nct02697734 （line 4）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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