Modified-Release Hydrocortisone in Congenital Adrenal Hyperplasia
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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.
Originalsprog | Engelsk |
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Tidsskrift | The Journal of clinical endocrinology and metabolism |
Vol/bind | 106 |
Udgave nummer | 5 |
Sider (fra-til) | e2063-e2077 |
Antal sider | 15 |
ISSN | 0021-972X |
DOI | |
Status | Udgivet - 23 apr. 2021 |
Bibliografisk note
Publisher Copyright:
© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.
ID: 282038522