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Switching Patients With Congenital Adrenal Hyperplasia to Modified-Release Hydrocortisone Capsules: Relative
Richard John M Ross1, Wiebke Arlt2,3, Aude Brac de la Perriere4
1University of Sheffield, Sheffield, UK.
Clinical Endocrinology
|May 16, 2025
Summary
Modified-release hydrocortisone capsules (MRHC) offer comparable bioavailability to immediate-release hydrocortisone (IRHC) for congenital adrenal hyperplasia (CAH) treatment. Switching to MRHC twice daily is an effective protocol for managing CAH patients.
Area of Science:
- Pharmacokinetics and pharmacodynamics
- Endocrinology
- Drug development
Background:
- Modified-release hydrocortisone capsules (MRHC) are utilized for hormone replacement therapy in congenital adrenal hyperplasia (CAH).
- MRHC aims to mimic the physiological circadian cortisol rhythm, crucial for managing CAH.
- Standard therapy often involves immediate-release hydrocortisone (IRHC), which may not fully replicate natural cortisol patterns.
Purpose of the Study:
- To assess the relative bioavailability of MRHC compared to IRHC in healthy individuals.
- To establish an optimal protocol for transitioning CAH patients from IRHC to MRHC therapy.
- To evaluate the efficacy of MRHC in improving hormonal control in CAH patients.
Main Methods:
- A crossover study was conducted in healthy participants to compare the bioavailability of MRHC and IRHC.
- A post hoc analysis of a Phase 3 clinical trial data was performed on CAH patients switched to MRHC.
- Hormonal levels (17-hydroxyprogesterone and androstenedione) were measured to assess treatment effectiveness.
Main Results:
- Twenty-four healthy males demonstrated comparable bioavailability between 20 mg MRHC and 20 mg IRHC tablets (AUC ratio 108%).
- In CAH patients, switching to MRHC twice daily at the same total daily dose resulted in significant reductions in 17-hydroxyprogesterone and androstenedione levels after 4 weeks compared to continuing IRHC.
- The observed hormonal improvements in the MRHC group were statistically significant (p < 0.001 and p = 0.01).
Conclusions:
- MRHC exhibits comparable bioavailability to IRHC, supporting its use in hydrocortisone replacement therapy.
- A twice-daily MRHC regimen, initiated at the same total daily dose as IRHC, is an effective strategy for managing CAH.
- This optimized dosing protocol facilitates the transition to MRHC, potentially improving circadian cortisol rhythm restoration in CAH patients.
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