Modified-Release Hydrocortisone in Congenital Adrenal Hyperplasia.

Autor: Merke DP; National Institutes of Health Clinical Center, Bethesda, Maryland, USA.; The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA., Mallappa A; National Institutes of Health Clinical Center, Bethesda, Maryland, USA., Arlt W; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.; Department of Endocrinology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK., Brac de la Perriere A; Hospices Civils de Lyon, Fédération d'Endocrinologie, Groupement hospitalier Est, Bron Cedex, France., Lindén Hirschberg A; Department of Women's and Children's Health, Karolinska Institutet and Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden., Juul A; Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Newell-Price J; University of Sheffield, Sheffield, UK., Perry CG; Queen Elizabeth University Hospital, Glasgow, UK., Prete A; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.; Department of Endocrinology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK., Rees DA; Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK., Reisch N; Medizinische Klinik IV, Klinikum der Universität München, Munich, Germany., Stikkelbroeck N; Radboud University Medical Centre, GA Nijmegen, the Netherlands., Touraine P; Department of Endocrinology and Reproductive Medicine, Pitie Salpêtriere Hospital, France.; Sorbonne University, Center for Rare Endocrine and Gynecological Disorders, Paris, France., Maltby K; Diurnal Ltd, Cardiff, UK., Treasure FP; Peter Treasure Statistical Services Ltd, Kings Lynn, UK., Porter J; Diurnal Ltd, Cardiff, UK., Ross RJ; University of Sheffield, Sheffield, UK.; Diurnal Ltd, Cardiff, UK.
Jazyk: angličtina
Zdroj: The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2021 Apr 23; Vol. 106 (5), pp. e2063-e2077.
DOI: 10.1210/clinem/dgab051
Abstrakt: 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.
(© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)
Databáze: MEDLINE