Merke, D.P., Mallappa, A., Arlt, W. et al. (14 more authors) (2021) Modified-release hydrocortisone in congenital adrenal hyperplasia. The Journal of Clinical Endocrinology & Metabolism, 106 (5). e2063-e2077. ISSN 0021-972X
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. |
Keywords: | congenital adrenal hyperplasia; 21-hydroxylase deficiency; glucocorticoid; hydrocortisone; adrenal insufficiency |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number DIURNAL LTD nan SHEFFIELD TEACHING HOSPITALS NHS FOUNDATION TRUST nan |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 08 Mar 2021 16:16 |
Last Modified: | 15 Feb 2022 14:11 |
Status: | Published |
Publisher: | The Endocrine Society |
Refereed: | Yes |
Identification Number: | 10.1210/clinem/dgab051 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:170974 |