MON-481 Glucocorticoid (GC) Dosing Across Adults and Children with Congenital Adrenal Hyperplasia (CAH)

Abstract Disclosure: A. Khattab: Spruce Biosciences, Inc, Neurocrine Biosciences, Inc. R.J. Auchus: Neurocrine Biosciences, Inc, Neurocrine UK, LTD, Spruce Biosciences, Inc, Corcept Therapeutics, Crinetics Pharmaceuticals, Recordati Rare Diseases, Adrenas Therapeutics, Mineralys Pharmaceuticals, Quest Diagnostics, Xeris Pharmaceuticals, Novo Nordisk, H Lundbeck A/S, Sparrow Pharmaceuticals, Astellas Pharmaceuticals, Acerand Therapeutics. T.A. Bachega: Crinetics Pharmaceuticals, Novo Nordisk. J. Kim: None. M.E. Geffner: Adrenas Therapeutics, Diurnal, Neurocrine Biosciences, Inc, Novo Nordisk, Spruce Biosciences, Inc, AEterna Zentaris Inc, Ascendis Pharma, Eton Pharmaceuticals, Theratechnologies, Inc, Tolmar, Inc, McGraw-Hill, Up To Date. Background: CAH due to 21-hydroxylase deficiency (21OHD) is a chronic disorder requiring lifelong GC treatment. To provide GC replacement and suppress adrenal androgen production, GC doses higher than daily physiologic replacement (∼7 mg/m2 hydrocortisone or equivalent) are usually required. Using pooled data from three clinical trials in this form of CAH, we examined the relation between baseline GC dose and clinical characteristics. Methods: Phase 2 studies CAHmelia-203 (N=96; adults), CAHmelia-204 (N=100; adults), and CAHptain-205 (N=62; 2-65 yr) examined effectiveness of tildacerfont, an oral non-steroidal antagonist of the corticotropin-releasing factor type-1 receptor, in treating CAH. Using baseline data from these trials, we examined distribution of GC dose within baseline characteristics (CAH type, age, geographical region, sex, BMI, systolic/diastolic BP, LDL-C, HDL-C, triglycerides, HOMA-IR, and serum 17-hydroxyprogesterone [17-OHP] and androstenedione [A4]), as well as frequency of patients by GC dose categorized as ≤15 and >15 mg/m2/d and baseline characteristics. Mean differences in GC dose were calculated (along with 95% confidence intervals [CIs]). Results: In the pooled dataset (N=258; 143 females; 185 salt-wasting), mean (SD) age was 27 (14) yr; 30, 26, and 202 patients were in the 2-10 (pediatric), 11-17 (adolescent) and >17 yr (adult) groups, respectively. North America (NA), Europe (EU), and the rest of world (ROW) contributed 133, 74, and 51 patients, respectively. Mean BMI was 29.6 kg/m2 (8.3). Mean baseline 17-OHP and A4 were within normal limits in 4.7% and 27.9%, respectively, and mean HOMA-IR was 3.4 (2.7) in adults (N=188). Mean (SD) GC daily dose in all patients was 16.1 (5.0) mg/m2/day with equal numbers (122) of subjects on GC doses ≤ 15 and >15 mg/m2/day. Baseline characteristics where mean difference 95% CIs in GC dose (mg/m2/day) excluded 0 were: by age (yr) group: 13.4 (3.8) [pediatric], 14.9 (3.2) [adolescent], and 16.6 (5.2) [adult]; by region: 15.1 (NA), 16.8 (EU), and 17.7 (ROW); by 17-OHP normal 19.0 (3.4) and above upper limit of normal (ULN) 16.5 (5.0) and A4 normal 18.5 (4.9) and above ULN 15.1 (4.8). Discussion: In these clinical trials in CAH due to 21OHD, the mean daily GC dose was higher in adults than in both youth groups, in EU and ROW vs NA, and in patients with normal 17-OHP and A4 relative to those above the ULN. Presentation: Monday, July 14, 2025