SFEBES2021 Early Careers and Plenary Orals Clinical Endocrinology Trust Best Abstract Clinical (1 abstracts)
Phase 3 and extension study of modified-release hydrocortisone in the treatment of congenital adrenal hyperplasia
Deborah P Merke 1 , Ashwini Mallappa 1 , Wiebke Arlt 2 , Aude Brac De La Perriere 3 , Angelica Linden Hirschberg 4 , Anders Juul 5 , John D C Newell-Price 6 , Colin Graham Perry 7 , Alessandro Prete 2 , Aled Rees 8 , Nicole Reisch 9 , Monica Stikkelbroeck 10 , Philippe A Touraine 11 , Alexander Lewis 12 , Kerry Maltby 12 , Peter Treasure 13 , John Porter 12 & Richard John M Ross 12,6
1NIH, Bethesda, USA. 2University of Birmingham, Birmingham, UK; 3Hopital Louis Pradel, Bron, France; 4Karolinska Institutet, Stockholm, Sweden; 5Rigshospitalet, Copenhagen, Denmark; 6University of Sheffield, Sheffield, UK; 7Queen Elizabeth University Hospital, Glasgow, UK; 8Cardiff University, Cardiff, UK; 9Klinikum der Universität München, München, Germany; 10Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; 11GH Pitie Salpetriere, Paris, France; 12Diurnal Ltd, Cardiff, UK; 13Statistical Services Ltd, Kings Lynn, UK
Background: Patients with congenital adrenal hyperplasia (CAH) due to classic 21-hydroxylase deficiency have poor health outcomes. We compared disease control in CAH adults treated with modified release hydrocortisone (MRHC, Chronocort®, Diurnal Ltd) versus standard glucocorticoid (GC).
Methods: 6-month, Phase 3 study in 122 patients randomised to either MRHC twice daily or standard GC followed by safety extension study on MRHC. Patients had 24-hr 17-hydroxyprogesterone (17-OHP) profiling at baseline 4, 12 & 24 weeks. The primary endpoint was change from baseline to 24 weeks in logarithm mean of 24-hr standard deviation score (SDS) 17-OHP profile.
Results: Both groups improved hormonal control on intensive monitoring; however, the mean 24-hour 17-OHP SDS was lower on MRHC compared to standard GC at 4 weeks (P = 0.007) and 12 weeks (P = 0.019), but not at 24 weeks. At 24 weeks, MRHC compared to standard GC showed greater reduction in: 17-OHP SDS morning & afternoon (P = 0.044), 24 h AUC (P = 0.025), and variability (P < 0.001). Good disease control (09:00h serum 17OHP <36.4 nmol/l) was 52% at baseline and at 6 months 91% for MRHC and 71% for standard GC (P = 0.002). There were no adrenal crisis on MRHC and 3 on standard GC. In the ongoing extension study (221 patient years), there were 12 adrenal crises in 5 patients (5.4 / 100 patient years). Geomean 9am 17-OHP was within optimal range on median MRHC dose of 20mg daily. In 27 women aged <50yrs not using oral contraceptives or IUD, 9 patients reported improved menstruation, 4 became pregnant and there have been 4 partner pregnancies.
Conclusions: Twice daily MRHC improved control of CAH with most patients showing good disease control on an adrenal replacement dose of hydrocortisone and this was associated with patient reported clinical benefit, including restoration of menstruation and pregnancies.
Volume 77
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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