ECE2022 Rapid Communications Rapid Communications 2: Adrenal and Cardiovascular Endocrinology 1 (8 abstracts)
Modified release hydrocortisone capsules (MRHC, Efmody) improve control of congenital adrenal hyperplasia (CAH) on a lower glucocorticoid dose than standard treatment
Aled Rees 1 , Deborah P Merke 2 , Wiebke Arlt 3 , Aude Brac De La Periere 4 , Angelica Linden Hirschberg 5 , Anders Juul 6 , Ashwini Mallappa 7 , John D. C. Newell-Price 8 , Colin Graham Perry 9 , Alessandro Prete 3 , Nicole Reisch 10 , Monica Stikkelbroeck 11 , Philippe A Touraine 12 , Helen Coope 13 , John Porter 13 & Richard John M Ross 8
1Cardiff University, United Kingdom; 2NIH Clinical Center, Bethesda, United States; 3University of Birmingham, United Kingdom; 4Louis Pradel Hospital, Bron, France; 5Karolinska Institute, Sweden; 6Rigshospitalet, København, Denmark; 7AstraZeneca, Gaithersburg, United States; 8The University of Sheffield, United Kingdom; 9University of Glasgow, United Kingdom; 10Endokrinologie, Nephrologie und weitere Sektionen - Medizinische Klinik und Poliklinik IV - Campus Innenstadt, München, Germany; 11Radboud University Nijmegen, Nijmegen, Netherlands; 12University Hospitals Pitié Salpêtrière - Charles Foix, Paris, France; 13Diurnal Ltd, United Kingdom
Background: The therapeutic goal in CAH is androgen control on the lowest achievable glucocorticoid dose, preferably an adrenal replacement dose (15-25 mg hydrocortisone a day)1. However, the glucocorticoid dose required to control androgens frequently exceeds that required for adrenal replacement2. Modified-release hydrocortisone (MRHC) capsules, (Efmody, Diurnal Ltd, Cardiff, UK), replicate cortisol diurnal rhythm and improve CAH control compared to standard therapy3. We have examined whether MRHC can improve CAH control in patients receiving high dose standard treatment.
Methods: We reviewed the data of patients in the randomised study of standard treatment versus MRHC and selected those on >25 mg/day hydrocortisone dose equivalent (HDE=prednisolone dose 5 & dexamethasone 80)3 at study entry. Patients were assessed at 24 weeks after blinded dose titration aimed to bring 17OHP into the optimal range (<36 nmol/l) and A4 into the reference range. After 24 weeks, patients participated in an ongoing MHRC single arm extension study. Control of CAH was defined as 0900h 17OHP <36 nmol/l.
Results: At baseline 41% (n=43/105) of patients were on >25mg HDE/day standard treatment; 21/43 were female, mean baseline 0900h 17OHP was 106 nmol/l and 48% were uncontrolled. At 24 weeks 95% (n=21/22) of patients on MRHC were controlled on median 40 mg/day (mean 17OHP 10 nmol/l) and for standard treatment 81% were controlled on median 40 mg HDE/day (mean 17OHP 49 nmol/l). In the full cohort, there were no adrenal crises in the MRHC group and three in the standard treatment group (10.7/100 patient years). After 24 weeks 27 of the 43 patients entered the clinician-titrated, MRHC single-arm extension study. At the 18-month interim analysis 76% patients were in control with a median dose of 25 mg (52% ≤25 mg/day) and mean 17OHP 24 nmol/l. In the ongoing extension study of all patients on MRHC (221 patient years), there were 12 adrenal crises in 5 patients (5.4/100 patient years).
Conclusions: It is common in CAH patients for the glucocorticoid dose to exceed the recommended adrenal replacement dose and still ~50% of patients remain uncontrolled. MRHC controlled 17OHP in 95% patients who were previously on high dose standard therapy and over time it was possible to reduce the MRHC dose to an adrenal replacement dose in ~50% of patients and retain control in 75%.
References: 1. Speiser P., JCEM 2018 103 4043-4088.2. Prete A., EJE 2021 186 R1-R14.3. Merke DP., JCEM 2021 106 e2063-e2077.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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