Modified-Release Hydrocortisone in Congenital Adrenal Hyperplasia

Merke, Deborah P.; Mallappa, Ashwini; Arlt, Wiebke; Brac de la Perriere, Aude; Hirschberg, Angelica Linden; Juul, Anders; Newell-Price, John; Perry, Colin G.; Prete, Alessandro; Rees, D. Aled; Reisch, Nicole; Stikkelbroeck, Nike; Touraine, Philippe; Maltby, Kerry; Treasure, F. Peter; Porter, John und Ross, Richard J. (2021): Modified-Release Hydrocortisone in Congenital Adrenal Hyperplasia. In: Journal of Clinical Endocrinology & Metabolism, Bd. 106, Nr. 5, E2063-E2077

Abstract

Context: Standard glucocorticoid therapy in congenital adrenal hyperplasia (CAH) regularly fails to control androgen excess, causing glucocorticoid overexposure and poor health outcomes. Objective: We investigated whether modified-release hydrocortisone (MR-HC), which mimics physiologic cortisol secretion, could improve disease control. Methods: A 6-month, randomized, phase 3 study was conducted of MR-HC vs standard glucocorticoid, followed by a single-arm MR-HC extension study. Primary outcomes were change in 24-hour SD score (SDS) of androgen precursor 17-hydroxyprogesterone (17OHP) for phase 3, and efficacy, safety and tolerability of MR- HC for the extension study. Results: The phase 3 study recruited 122 adult CAH patients. Although the study failed its primary outcome at 6 months, there was evidence of better biochemical control on MR-HC, with lower 17OHP SDS at 4 (P =.007) and 12 (P =.019) weeks, and between 07:00h to 15:00h (P =.044) at 6 months. The percentage of patients with controlled 09:00h serum 17OHP (< 1200 ng/dL) was 52% at baseline, at 6 months 91% for MR-HC and 71% for standard therapy (P =.002), and 80% for MR-HC at 18 months' extension. The median daily hydrocortisone dose was 25 mg at baseline, at 6 months 31 mg for standard therapy, and 30 mg for MR-HC, and after 18 months 20 mg MR-HC. Three adrenal crises occurred in phase 3, none on MR-HC and 4 in the extension study. MR-HC resulted in patient-reported benefit including menses restoration in 8 patients (1 on standard therapy), and 3 patient and 4 partner pregnancies (none on standard therapy). Conclusion: MR-HC improved biochemical disease control in adults with reduction in steroid dose over time and patient-reported benefit.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0021-972X
• Sprache: Englisch