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<p>The primary treatment for active Cushing’s Syndrome (CS) is the surgical removal of the causative tumor. Alternative therapeutic strategies, particularly pharmaceutical approaches, are required when surgery is not feasible, unsuccessful, or in cases of recurrence. Osilodrostat, an adrenal steroidogenesis inhibitor, is approved in Europe and USA for adult patients with CS. The recommended strategy involves gradual titration to achieve eucortisolism, but this approach has limitations. Delayed disease control can be harmful in severe cases, and frequent clinical and laboratory monitoring may be challenging for some patients or during global health crises. To address these challenges, experts have introduced the block-and-replace (B&amp;R) strategy which they consider suitable for selected patients. Due to limited guidance on patient selection and safe implementation, a group of French experts (the authors) who had the opportunity to use osilodrostat outside of clinical trials developed a position statement on B&amp;R. They highlight that osilodrostat B&amp;R strategy is effective and safe, especially when other treatment options are less beneficial. This position paper, while offering a valuable clinical framework, is expert-driven rather than evidence-based, emphasizing the need for further studies, particularly randomized controlled trials, comparing B&amp;R and titration strategies across diverse populations.</p>

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Use of osilodrostat in a block-and-replace and titration strategy for cushing’s syndrome: a position paper by French experts

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月28日

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  • Frédéric Castinetti,
  • Jérôme Bertherat,
  • Philippe Chanson,
  • Gerald Raverot,
  • Jacques Young,
  • Antoine Tabarin

摘要

The primary treatment for active Cushing’s Syndrome (CS) is the surgical removal of the causative tumor. Alternative therapeutic strategies, particularly pharmaceutical approaches, are required when surgery is not feasible, unsuccessful, or in cases of recurrence. Osilodrostat, an adrenal steroidogenesis inhibitor, is approved in Europe and USA for adult patients with CS. The recommended strategy involves gradual titration to achieve eucortisolism, but this approach has limitations. Delayed disease control can be harmful in severe cases, and frequent clinical and laboratory monitoring may be challenging for some patients or during global health crises. To address these challenges, experts have introduced the block-and-replace (B&R) strategy which they consider suitable for selected patients. Due to limited guidance on patient selection and safe implementation, a group of French experts (the authors) who had the opportunity to use osilodrostat outside of clinical trials developed a position statement on B&R. They highlight that osilodrostat B&R strategy is effective and safe, especially when other treatment options are less beneficial. This position paper, while offering a valuable clinical framework, is expert-driven rather than evidence-based, emphasizing the need for further studies, particularly randomized controlled trials, comparing B&R and titration strategies across diverse populations.