Matching-Adjusted Indirect Comparison of Osilodrostat Versus Metyrapone for the Treatment of Cushing's Syndrome.

IF 3.4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2025-05-29 DOI:10.1007/s12325-025-03229-0

Conor Hickey, Beatrice Gueron, Fabian Schmidt, Emma Tyas, Grzegorz Binowski, Rosario Pivonello

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引用次数: 0

Abstract

Introduction: Cushing's syndrome (CS) is a rare, chronic condition caused by prolonged exposure to elevated levels of circulating cortisol, and characterized by high morbidity and mortality. The primary treatment option for CS is surgery; however, medical therapy may be useful when surgery is unsuitable, refused, or has not been curative, or a rapid control of hypercortisolism is required. While osilodrostat and metyrapone are two treatments for controlling cortisol levels, they have not been compared directly in a clinical trial. This study evaluated the comparative efficacy and tolerability of osilodrostat versus metyrapone for the treatment of CS using indirect treatment comparison methods.

Methods: Unanchored matching-adjusted indirect comparison was used to synthesize relative treatment effects by reweighting patient-level data from two clinical trials for osilodrostat to published aggregate data for metyrapone. Efficacy endpoints included complete response (CR), defined as mean urinary free cortisol ≤ 1.0 × the upper limit of normal, at Weeks 12, 24, and 36. Tolerability endpoints included all-cause treatment discontinuation and treatment discontinuation due to lack of efficacy (LoE) or adverse events (AEs).

Results: The base case analysis demonstrated that osilodrostat provides increased odds of CR versus metyrapone at Week 12 [odds ratio (OR) 2.75; 95% confidence interval (CI) 1.29, 5.88], Week 24 (OR 3.28; 95% CI 1.58, 6.84) and Week 36 (OR 10.50; 95% CI 1.84, 59.96), implying a greater proportion of patients experience normalized cortisol levels at these time-points. Although the base case analysis showed that the odds of all-cause discontinuation and discontinuation due to LoE or AEs were numerically lower for osilodrostat, the evidence was insufficient to show a statistically significant difference.

Conclusion: These analyses show that osilodrostat increases the odds of achieving CR at Weeks 12, 24, and 36 versus metyrapone, demonstrating that osilodrostat is a more efficacious treatment option for normalizing cortisol levels in CS patients.

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奥西洛司他与美吡酮治疗库欣综合征的匹配校正间接比较。

库欣综合征（CS）是一种罕见的慢性疾病，由长期暴露于循环皮质醇水平升高引起，以高发病率和高死亡率为特征。CS的主要治疗选择是手术；然而，当手术不合适、被拒绝或无法治愈，或需要快速控制高皮质醇血症时，药物治疗可能是有用的。虽然奥西洛司他和美替拉酮是控制皮质醇水平的两种治疗方法，但它们还没有在临床试验中直接进行比较。本研究采用间接治疗比较法评价奥西洛他与美吡酮治疗CS的比较疗效和耐受性。方法：采用非锚定匹配调整间接比较，通过将两项奥西洛他临床试验的患者水平数据重新加权到已发表的美吡酮总体数据，来综合相对治疗效果。疗效终点包括完全缓解（CR），定义为平均尿游离皮质醇≤1.0倍正常上限，在第12周，24周和36周。耐受性终点包括全因治疗停药和因缺乏疗效（LoE）或不良事件（ae）而停药。结果：基础病例分析表明，在第12周，奥西洛他与美吡酮相比，CR的发生率更高[比值比（OR） 2.75；95%可信区间（CI） 1.29, 5.88]，第24周(OR 3.28；95% CI 1.58, 6.84)和第36周(OR 10.50；95% CI 1.84, 59.96)，这意味着在这些时间点，更大比例的患者经历了正常化的皮质醇水平。虽然基本病例分析显示，奥西洛司他全因停药和因LoE或ae停药的几率在数值上较低，但证据不足以显示统计学上的显著差异。结论：这些分析表明，与美替拉酮相比，奥西洛他增加了在第12、24和36周达到CR的几率，表明奥西洛他是一种更有效的治疗选择，可以使CS患者的皮质醇水平正常化。

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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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

期刊介绍： Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.