Modified-release hydrocortisone (Efmody®) in children with congenital adrenal hyperplasia: a retrospective registry study.

BACKGROUND

Replacement therapy for congenital adrenal hyperplasia (CAH) in childhood includes hydrocortisone and, in salt-wasting forms, addition of fludrocortisone. Immediate-release hydrocortisone often fails to adequately suppress early morning 17-hydroxyprogesterone (17OHP) levels. Hydrocortisone modified-release capsules (HMRC, Efmody®) were approved by the EMA in 2021 for the treatment of patients aged ≥12 years with CAH. This study evaluates the efficacy and safety of HMRC in children and adolescents based on real-world data collected from the I-CAH registry.

METHODS

A single-center retrospective analysis of children with CAH was conducted. Linear mixed models (LMMs) were used to calculate pre-post comparisons of 17OHP saliva profiles, growth rate, bone age, body mass index, hydrocortisone and fludrocortisone dosage, blood pressure, and safety parameters before and during HMRC therapy (study registration, https://drks.de/search/de, DRKS00038319).

FINDINGS: The median age of the 36 children with CAH at the time of treatment switching to HMRC was 10 years (interquartile range [IQR]: 8-14 years). Of these, 15 were prepubertal and 21 were (post)pubertal. HMRC therapy was associated with a deceleration of previously increased growth velocity (pre-switch: 0.1 SDS/year, 95% CI: 0.0 to 0.2; post-switch: -0.1 SDS/year, 95% CI: -0.2 to 0.1) and with a reduction of median difference of bone age and chronological age by 0.50 years (IQR -1.17-0.27, range -2.2-2.00). Mean hydrocortisone dose increased by 2.4 mg/m²/day during HMRC treatment. Mean morning 17OHP concentrations significantly decreased from 337 ng/L (95% CI: 240-437) to 214 ng/L (95% CI: 155-294) after switching to HMRC treatment. No adrenal crisis was observed.

INTERPRETATION: Twice-daily HMRC therapy can also improve CAH therapy in children and adolescents in terms of hormonal control and growth.