SAT304 Improved Biochemical Control With Dose Reduction In Chronic Glucocorticoid Therapy: A Phase III Extension Study Of Chronocort (Efmody) In The Treatment Of Congenital Adrenal Hyperplasia (CAH)

Abstract

Abstract Disclosure: R.J. Ross: Employee; Self; Diurnal, A Neurocrine Biosciences Company. D.P. Merke: None. A. Mallappa: None. W. Arlt: None. A. Brac de la Perriere: None. A.L. Hirschberg: None. A. Juul: None. J.D. Newell-Price: None. C.G. Perry: None. A. Prete: None. A. Rees: None. N. Reisch: None. M. Stikkelbroeck: None. P.A. Touraine: None. N. Aslam: Employee; Self; Diurnal Ltd, a Neurocrine Biosciences company. H. Coope: Employee; Self; Diurnal Ltd, a Neurocrine Biosciences company. J. Porter: Employee; Self; Diurnal Ltd, a Neurocrine Biosciences Company. Background: Management of congenital adrenal hyperplasia (CAH) involves replacing cortisol deficiency and controlling raised adrenal androgens. Guidelines recommend a target daily hydrocortisone dose of ≤25mg to replace adrenal insufficiency; however, cohort studies show doses >25mg are used to control androgens in CAH patients. Modified-release hydrocortisone (MRHC) capsules, (Efmody, UK), replicate the cortisol diurnal rhythm and improve the control of CAH compared to standard glucocorticoid therapy1. This post-hoc analysis examines total glucocorticoid daily dose and 9am 17-hydroxyprogesterone (17-OHP) levels in MRHC treated patients after 24 months in an ongoing MRHC single-arm extension study. Methods: All patients (n=71) that completed 24 months in the extension study at the time of the interim data cut were reviewed. Patients were recruited predominantly from the 6-month randomised phase III study comparing MRHC to standard glucocorticoid with blind titration of MRHC doses. In this extension phase the dose was titrated by the investigator on the 17-OHP and androstenedione levels at 4, 12, 24 weeks and 6 monthly. Androgen control was defined as 17-OHP <36 nmol/L (<1190 ng/dL). After 24 months, 64 of the patients had 9am 17-OHP data. A Wilcoxon-signed ranks test was performed to assess the change in total MRHC daily dose from baseline to 24 months. A Fisher’s exact test was performed to determine if the number of patients that achieved androgen control on a hydrocortisone (HC) dose ≤25 mg showed a statistically significant increase. Results: The median daily HC dose at baseline was 30mg (Inter-quartile range (IQR) 25-40) and at 24 months had reduced to 20mg (IQR 15-25), p<0.0001.Quadrant analysis revealed the following data: Baseline: &gt 36nmol/L 17-OHP & &lt 25mg/day 9/71 (13%). &gt 36nmol/L 17-OHP & &gt 25mg/day18/71 (25%). &lt 36nmol/L 17-OHP & &lt 25mg/day 22/71 (31%). &lt 36nmol/L 17-OHP & &gt 25mg/day 22/71 (31%). 24 months: &gt 36nmol/L 17-OHP & &lt 25mg/day 16/64 (25%). &gt 36nmol/L 17-OHP & &gt 25mg/day 2/64 (3%). &lt 36nmol/L 17-OHP & &lt 25mg/day 31/64 (48%). &lt 36nmol/L 17-OHP & &gt 25mg/day 15/64 (23%). 48% of subjects achieved androgen control based on 9am 17-OHP level at a HC dose ≤ 25 mg following 24 months of MRHC treatment compared with 31% at baseline (31% vs 48%, p= 0.03 by Fisher’s exact test). Conclusions: After 24 months of MRHC treatment the median daily HC dose was reduced from a median of 30mg to 20mg and the number of patients achieving androgen control based on 9am 17-OHP while receiving HC ≤25mg/day increased significantly.