Modified-Release Hydrocortisone in Congenital Adrenal Hyperplasia

Area of Science:

• Endocrinology
• Pharmacology
• Genetics

Background:

• Standard glucocorticoid therapy for congenital adrenal hyperplasia (CAH) often inadequately controls androgen excess.
• This can lead to glucocorticoid overexposure and adverse health outcomes in patients.

Purpose of the Study:

• To investigate the efficacy of modified-release hydrocortisone (MR-HC) in improving disease control in CAH patients.
• MR-HC aims to mimic physiologic cortisol secretion patterns.

Main Methods:

• A 6-month randomized phase 3 study comparing MR-HC to standard glucocorticoid therapy.
• Followed by a single-arm MR-HC extension study for long-term assessment.
• Primary outcomes included changes in 17-hydroxyprogesterone (17OHP) standard deviation scores (SDS) and assessment of MR-HC's efficacy, safety, and tolerability.

Main Results:

• While the primary outcome was not met at 6 months, MR-HC showed improved biochemical control, with lower 17OHP SDS at multiple time points.
• A significantly higher percentage of patients on MR-HC achieved controlled 09:00h serum 17OHP levels compared to standard therapy.
• MR-HC was associated with a reduction in daily hydrocortisone dose over 18 months and reported patient benefits like menses restoration and increased pregnancies.

Conclusions:

• Modified-release hydrocortisone (MR-HC) demonstrates potential for improved biochemical disease control in adult CAH patients.
• The therapy facilitated a reduction in steroid dosage over time.
• MR-HC provided significant patient-reported benefits, highlighting its clinical utility.