Comparison of modified-release hydrocortisone capsules versus prednisolone in the treatment of congenital adrenal hyperplasia

• Published in: Endocrine Connections 2024-08, Vol.13 (8), p.1-8
• Main Authors: Rees, Dafydd Aled, Merke, Deborah P, Arlt, Wiebke, Brac De La Perriere, Aude, Hirschberg, Angelica Linden, Juul, Anders, Newell-Price, John, Prete, Alessandro, Reisch, Nicole, Stikkelbroeck, Nike M, Touraine, Philippe A, Lewis, Alex, Porter, John, Coope, Helen, Ross, Richard J
• Format: Article
• Language: English
• Subjects: adrenal insufficiency; cah; congenital adrenal hyperplasia; cortisol; hydrocortisone; prednisolone; prednisone
• ISSN: 2049-3614; 2049-3614
• DOI: 10.1530/EC-24-0150

Prednisolone and prednisone are recommended treatment options for adults with congenital adrenal hyperplasia (CAH); however, there is no randomised comparison of prednis(ol)one with hydrocortisone. Six-month open-label randomised phase 3 study and interim analysis of a single-arm extension study was the design of the study. The method of the study was hydrocortisone dose equivalent and 09:00-h 17-hydroxyprogesterone (17OHP) from 48 patients taking prednis(ol)one at baseline. At baseline, the median hydrocortisone dose equivalent was 30 mg/day and 17OHP was < 36 nmol/L (3× upper limit of normal) in 56% of patients. Patients were randomised to continue prednis(ol)one or switch to modified-release hydrocortisone capsule (MRHC) at the same hydrocortisone-equivalent dose. At 4 weeks, 94% on MRHC and 71% on prednis(ol)one had 17OHP < 36 nmol/L. At 18 months in the extension study of MRHC, the median MRHC dose was 20 mg/day and 82% had 17OHP < 36 nmol/L. The per cent of patients with 17OHP < 36 nmol/L on a hydrocortisone dose equivalent ≤ 25 mg/day was greater at 18 months in the extension study on MRHC than while on prednis(ol)one at baseline: 57% vs 27%, P = 0.04. In the randomised study, no patients had an adrenal crisis on MRHC and one on prednisolone. In the extension study (221 patient years), there were 12 adrenal crises in 5 patients (5.4/100 patient years). MRHC reduces 17OHP at 09:00 h compared to prednis(ol)one and the dose of MRHC can be down-titrated over time in the majority of patients.