Modified-Release Hydrocortisone in Congenital Adrenal Hyperplasia
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Modified-Release Hydrocortisone in Congenital Adrenal Hyperplasia. / Merke, Deborah P.; Mallappa, Ashwini; Arlt, Wiebke; Brac de la Perriere, Aude; Lindén Hirschberg, Angelica; 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; Ross, Richard J.
I: The Journal of clinical endocrinology and metabolism, Bind 106, Nr. 5, 23.04.2021, s. e2063-e2077.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Modified-Release Hydrocortisone in Congenital Adrenal Hyperplasia
AU - Merke, Deborah P.
AU - Mallappa, Ashwini
AU - Arlt, Wiebke
AU - Brac de la Perriere, Aude
AU - Lindén Hirschberg, Angelica
AU - Juul, Anders
AU - Newell-Price, John
AU - Perry, Colin G.
AU - Prete, Alessandro
AU - Rees, D. Aled
AU - Reisch, Nicole
AU - Stikkelbroeck, Nike
AU - Touraine, Philippe
AU - Maltby, Kerry
AU - Treasure, F. Peter
AU - Porter, John
AU - Ross, Richard J.
N1 - Publisher Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2021/4/23
Y1 - 2021/4/23
N2 - 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.
AB - 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.
KW - 21-hydroxylase deficiency
KW - adrenal insufficiency
KW - congenital adrenal hyperplasia
KW - glucocorticoid
KW - hydrocortisone
U2 - 10.1210/clinem/dgab051
DO - 10.1210/clinem/dgab051
M3 - Journal article
C2 - 33527139
AN - SCOPUS:85105760441
VL - 106
SP - e2063-e2077
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 5
ER -
ID: 282038522