Biochemical control with dose reduction in chronic glucocorticoid therapy over 4 years: A phase III extension study of Chronocort (Efmody) in the treatment of Congenital Adrenal Hyperplasia (CAH)

M. Ross Richard John; Deborah P. Merke; Wiebke Arlt; La Perriere Aude Brac De; Angelica Hirschberg; John D.C. Newell-Price; Alessandro Prete; Aled Rees; Nicole Reisch; Marcus Quinkler; Philippe A. Touraine; Kerry Maltby; Jo Quirke; Naila Aslam; Helen Coope; John Porter

doi:10.1530/endoabs.99.RC3.1

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Endocrine Abstracts (2024) 99 RC3.1 | DOI: 10.1530/endoabs.99.RC3.1

ECE2024 Rapid Communications Rapid Communications 3: Adrenal and Cardiovascular Endocrinology | Part I (7 abstracts)

Biochemical control with dose reduction in chronic glucocorticoid therapy over 4 years: A phase III extension study of Chronocort (Efmody) in the treatment of Congenital Adrenal Hyperplasia (CAH)

Richard John M. Ross ¹ , Deborah P. Merke ² , Wiebke Arlt ³ , Aude Brac De La Perriere ⁴ , Angelica Hirschberg ⁵ , John D.C. Newell-Price ¹ , Alessandro Prete ⁶ , Aled Rees ⁷ , Nicole Reisch ⁸ , Marcus Quinkler ⁹ , Philippe A. Touraine ¹⁰ , Kerry Maltby ¹¹ , Jo Quirke ¹¹ , Naila Aslam ¹¹ , Helen Coope ¹¹ & John Porter ¹¹

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Author affiliations

¹The University of Sheffield, United Kingdom; ²National Institutes of Health, Bethesda, United States; ³MRC Laboratory of Medical Sciences, United Kingdom; ⁴Louis Pradel Hospital, Bron, France; ⁵Karolinska Institute, Sweden; ⁶University of Birmingham, United Kingdom; ⁷Cardiff University, United Kingdom; ⁸Klinikum der Universität München, München, Germany; ⁹Charlottenburg, Berlin, Germany, ¹⁰University Hospitals Pitié Salpêtrière - Charles Foix, Paris, France, ¹¹Diurnal, United Kingdom

Background: Management of CAH involves replacing cortisol deficiency and reducing raised adrenal androgens, however the supraphysiological glucocorticoid doses often required to treat hyperandrogenism are associated with poor long-term health outcomes. Modified-release hydrocortisone (MRHC) capsules, Efmody, replicate cortisol diurnal rhythm and improve control of CAH compared to standard glucocorticoid therapy. Here we report changes in glucocorticoid daily dose and 9am 17-hydroxyprogesterone (17-OHP) and androstenedione (A4) in MRHC-treated patients after 48 months in the MRHC single-arm extension study.

Methods: Participants completing MRHC Ph2 and Ph3 studies were eligible to enter a single-arm, open-label extension study. Visits occurred at baseline, weeks 4, 12, 24 and 6-monthly thereafter. MRHC doses were adjusted on the basis of an adrenal insufficiency checklist, and measurement of A4 and 17-OHP at 9am and 1pm, targeting 17-OHP to <36 nmol/l and A4 into the reference range. Participants that completed 48 months in the extension study were reviewed. Participants were considered responders when 9am 17OHP ≤36 nmol/l or A4 ≤7nmol/l and hydrocortisone (HC) dose ≤25 mg/day.

Results: Data were available for 91 participants at baseline and 71 participants (61 with hormone blood results) at 48 months. The median daily HC dose (Inter-Quartile Range [IQR]) at baseline and 48 months were 30 mg (IQR 20–35) and 20 mg (IQR 15–25), respectively (nominal P<0.0001). Geomean (95% CI) 17-OHP was 15.84 (10.32–24.31) and 11.34 (7.048–18.23) nmol/l at baseline and 48 months, respectively. Geomean A4 (95% CI) was 2.242 (1.669–3.012) and 2.092 (1.604–2.727) nmol/l at baseline and 48 months, respectively. Quadrant analysis showed the following:


			Dose
		≤25 mg/day	>25 mg/day
Baseline	>36 nmol/l 17-OHP	14/91 (15%)	21/91 (23%)
	≤36nmol/l 17-OHP	29/91 (32%)	27/91 (30%)
48 months	>36 nmol/l 17-OHP	15/61 (24%)	3/61 (5%)
	≤36 nmol/l 17-OHP	31/61 (51%)	12/61 (20%)
Responder status 51% vs 32% at baseline, P=0.0274 by Fisher’s exact test.

Conclusions: After 48 months of MRHC treatment the median daily HC dose was reduced from a median of 30mg to 20mg and the number of patients achieving responder status based on 9am 17-OHP or A4 while receiving HC ≤25 mg/day increased.