ESPE Yearbook of Paediatric Endocrinology

J Clin Endocrinol Metab. 2025; 110(2):334-344. PMID: 39097643 doi: 10.1210/clinem/dgae521. https://pubmed.ncbi.nlm.nih.gov/39097643/

Brief summary: This paper presents a post-hoc analysis of data from a randomized, double-blind, placebo- and prednisone-controlled 24-week trial of vamorolone with a 24-week crossover extension.

Comment: This study assessed the frequency of adrenal suppression induced by vamorolone and prednisone in pediatric Duchenne’s muscular dystrophy (DMD) and cortisol concentrations thresholds using a monoclonal antibody immunoassay in patients with pediatric DMD. It was previously suggested that Vamorolone, with distinct chemical structure and differences in mechanism of action, may be a safer alternative to prednisone for treating DMD, offering similar anti-inflammatory efficacy (via the glucocorticoid receptor), with fewer side effects related to growth and bone health (1). Mechanistically, Vamorolone shows reduced positive gene transcriptional activity (transactivation) than corticosteroids but retains the inhibition of nuclear factor κB proinflammatory pathways (transrepression), while it has been suggested that the lack of effect of modulatory 11β-hydroxysteroid dehydrogenase enzymes, explains the fewer corticosteroid-associated bone morbidities (2). In addition, Vamorolone is a potent antagonist of the mineralocorticoid receptor, with the potential to reduce cardiomyocyte pathology frequently seen in DMD (3). Therefore, a thorough evaluation of adrenal function in these patients both with various stimulated cortisol concentrations cut-offs and various Vamorolone doses as compared to standard prednisone (0.75 mg/kg/day) in pediatric DMD, is of clinical importance.

Indeed, this study showed that adrenal insufficiency after Vamorolone and prednisone was frequent; when associated with Vamorolone adrenal insufficiency appeared dose dependent. The authors recommend hydrocortisone stress dosing in patients receiving Vamorolone.

References: 1. Guglieri M, Clemens PR, Perlman SJ, et al. Efficacy and Safety of Vamorolone vs Placebo and Prednisone Among Boys With Duchenne Muscular Dystrophy: A Randomized Clinical Trial. JAMA Neurol. 2022;79(10):1005–1014. doi: 10.1001/jamaneurol.2022.2480.2. Fenton, C.G., Doig, C.L., Fareed, S. et al. 11β-HSD1 plays a critical role in trabecular bone loss associated with systemic glucocorticoid therapy. Arthritis Res Ther 21, 188 (2019). https://doi.org/10.1186/s13075-019-1972-13. Heier RC, Yu Q, Fiorillo AA, Tully CB, Tucker A, Mazala DA, Uaesoontrachoon K, Srinivassane S, Damsker JM, Hoffman EP, Nagaraju K, Spurney CF. Life Science Alliance Feb 2019, 2 (1) e201800186; doi: 10.26508/lsa.201800186