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

BACKGROUND

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.

OBJECTIVE

To assess 17-hydroxyprogesterone (17OHP) levels and glucocorticoid dose in CAH comparing prednis(ol)one versus modified-release hydrocortisone (MRHC).

DESIGN

Six-month open-label randomised phase 3 study and interim analysis of a single-arm extension study.

METHODS

Hydrocortisone dose equivalent and 09:00h 17OHP from 48 patients taking prednis(ol)one at baseline.

RESULTS

At baseline, the median hydrocortisone dose equivalent was 30 mg /day and 17OHP was <36nmol/l (3X upper limit of normal) in 56% of patients. Patients were randomised to continue prednis(ol)one or switch to MRHC at the same hydrocortisone equivalent dose. At 4 weeks, 94% on MRHC and 71% on prednis(ol)one had 17OHP <36nmol/l. At 18 months in the extension study of MRHC, the median MRHC dose was 20 mg /day and 82% had 17OHP <36nmol/l. The percent of patients with 17OHP <36nmol/l on a hydrocortisone dose equivalent ≤25mg /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).

CONCLUSIONS

MRHC reduces 17OHP at 09:00h compared to prednis(ol)one and the dose of MRHC can be down-titrated over time in the majority of patients.