Switching Patients With Congenital Adrenal Hyperplasia to Modified‐Release Hydrocortisone Capsules: Relative Bioavailability and Disease Control

作者：Richard John M. Ross, Wiebke Arlt, Aude Brac de la Perrière, Angelica Lindén Hirschberg, Anders Juul, Deborah P. Merke, John D C Newell-Price, Alessandro Prete, Aled Rees, Nicole Reisch, Monica Stikkelbroeck, Philippe A. Touraine, Kerry Maltby, J. F. Quirke, Helen Coope, John B. Porter · 发表于：Clinical Endocrinology · 年份：2025 · DOI：10.1111/cen.15275 · 被引用次数：3 · 研究领域：Sexual Differentiation and Disorders、Adrenal Hormones and Disorders、Hormonal and reproductive studies

BACKGROUND: Replacement therapy with modified-release hydrocortisone capsules (MRHC) restores the physiological circadian cortisol rhythm in congenital adrenal hyperplasia (CAH). AIMS: To determine the relative bioavailability of MRHC and evaluate an optimal protocol to switch CAH patients from standard therapy to MRHC. METHODS: (1): Crossover study in healthy participants comparing relative bioavailability of MRHC with immediate-release hydrocortisone (IRHC). (2): Post hoc analysis of first 4 weeks of phase 3 MRHC study when CAH patients were switched to MRHC. RESULTS: was 2650 versus 2450 h*nmol/L, ratio of 108% (90% confidence interval (CI) 103%-113%). In the phase 3 study, 122 CAH patients were recruited of which 63 patients were managed with IRHC alone at baseline; 31 of 63 were randomised to continue IRHC and 32 of 63 were randomised to switch to MRHC on the same daily dose but given twice daily. At 4 weeks, a greater reduction in both the 09:00 h 17-hydroxyprogesterone and androstenedione was observed in the MRHC group compared to the IRHC group; p < 0.001 and p = 0.01, respectively. CONCLUSIONS: MRHC showed comparable bioavailability to IRHC based on cortisol AUC after 20 mg administration. Switching patients treated with IRHC to a twice daily MRHC regimen on the same daily dose (giving approximately two thirds of the dose at night) is an effective protocol for starting MRHC treatment.