Document Type

Article

Publication Date

8-4-2024

Keywords

adrenal suppression, adrenal insufficiency, prednisone, vamorolone, Duchenne muscular dystrophy

Abstract

Context: Vamorolone, a novel “dissociative” steroid, demonstrated similar efficacy in muscle function relative to prednisone 0.75 mg/kg/day but improved linear growth and bone turnover markers in a randomized trial of pediatric Duchenne muscular dystrophy (DMD). Objectives: To determine the frequency of adrenal suppression (AS) induced by vamorolone and prednisone in pediatric DMD and to assess cortisol thresholds using a monoclonal antibody immunoassay. Methods: Post hoc analysis of cortisol levels was performed on data from a randomized, double-blind, placebo- and prednisone-controlled 24- week trial of vamorolone with a 24-week crossover extension. Morning and ACTH-stimulated cortisol levels were measured using the Elecsys II immunoassay, with AS defined as a stimulated cortisol of /L (“historical threshold”) and /L (“revised threshold”). Results: Mean age at enrolment was 5.41 ± 0.86 years (n = 118). At week 24, the proportion of participants with AS using the historical and revised cortisol thresholds, respectively, were as follows: prednisone 0.75 mg/kg/day = 100% (25/25) and 92.0% (23/25); vamorolone 6 mg/ kg/day = 95.2% (20/21) and 90.5% (19/21); vamorolone 2 mg/kg/day = 84.2% (16/19) and 47.5% (9/19); and placebo = 20.0% (4/20) and 0% (0/20). Morning and peak ACTH-stimulated cortisol were strongly correlated in steroid-treated boys (Spearman correlation week 48 = 0.83). Conclusion: AS after vamorolone and prednisone was frequent and vamorolone-associated AS appeared dose-dependent. A lower stimulated cortisol threshold may be appropriate when using a monoclonal assay. We recommend hydrocortisone for glucocorticoid stress dosing in patients receiving vamorolone.

Comments

10.1210/clinem/dgae521

Research on behalf of the CINRG Vamorolone 004 Investigators

Publisher Attribution

© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.

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