Ahmet Alexandra, Tobin Rebecca, Dang Utkarsh J, Rooman Raoul, Guglieri Michela, Clemens Paula R, Hoffman Eric P, Ward Leanne M
Division of Endocrinology, Children's Hospital of Eastern Ontario and Department of Pediatrics, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada.
Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario K1H 8L1, Canada.
J Clin Endocrinol Metab. 2025 Jan 21;110(2):334-344. doi: 10.1210/clinem/dgae521.
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).
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.
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 <500 nmol/L ("historical threshold") and <400 nmol/L ("revised threshold").
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).
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.
新型“解离型”类固醇药物瓦莫洛龙在小儿杜氏肌营养不良症（DMD）的一项随机试验中，相对于泼尼松0.75 mg/kg/天，在肌肉功能方面显示出相似的疗效，但改善了线性生长和骨转换标志物。
确定小儿DMD中瓦莫洛龙和泼尼松引起肾上腺抑制（AS）的频率，并使用单克隆抗体免疫测定法评估皮质醇阈值。
对一项为期24周的瓦莫洛龙随机、双盲、安慰剂和泼尼松对照试验的数据进行皮质醇水平的事后分析，并进行为期24周的交叉延长。使用Elecsys II免疫测定法测量早晨和促肾上腺皮质激素（ACTH）刺激后的皮质醇水平，AS定义为刺激后的皮质醇<500 nmol/L（“历史阈值”）和<400 nmol/L（“修订阈值”）。
入组时的平均年龄为5.41±0.86岁（n = 118）。在第24周时，分别使用历史和修订皮质醇阈值时出现AS的参与者比例如下：泼尼松0.75 mg/kg/天=100%（25/25）和92.0%（23/25）；瓦莫洛龙6 mg/kg/天=95.2%（20/21）和90.5%（19/21）；瓦莫洛龙2 mg/kg/天=84.2%（16/19）和47.5%（9/19）；安慰剂=20.0%（4/20）和0%（0/20）。在接受类固醇治疗的男孩中，早晨和ACTH刺激后的皮质醇峰值密切相关（第48周Spearman相关性=0.83）。
瓦莫洛龙和泼尼松治疗后AS很常见，且与瓦莫洛龙相关的AS呈剂量依赖性。使用单克隆测定法时，较低的刺激皮质醇阈值可能是合适的。我们建议在接受瓦莫洛龙治疗的患者中使用氢化可的松进行糖皮质激素应激给药。
