Neurocrine Biosciences, Inc. announced the publication of the first peer-reviewed expert recommendations to guide glucocorticoid dose reduction in patients with classic congenital adrenal hyperplasia treated with CRENESSITY (crinecerfont). The recommendations for clinicians treating classic congenital adrenal hyperplasia (CAH) patients with CRENESSITY are presented in two complementary manuscripts ? one focused on pediatric patients aged four to 17 years and one focused on adults.
The publications include the first structured, expert-driven algorithms for reducing supraphysiologic glucocorticoid (GC) dosing after initiating CRENESSITY in real-world clinical practice. CRENESSITY is approved as an adjunct treatment to GC replacement to control androgens in adult and pediatric patients four years of age and older with classic CAH. In addition to the protocols used in the CAHtalyst Pediatric and Adult Phase 3 clinical trials, clinicians now have expert-developed systematic approaches to adjusting GC doses in pediatric and adult patients treated with CRENESSITY.
These recommendations, grounded in both clinical trial and real-world clinical experience, recognize that treatment goals and clinical considerations differ meaningfully between children and adults and provide two distinct algorithms tailored to each population: Pediatric patients: The expert recommendations center on support to achieve normal growth and normalize bone age maturation and pubertal development while reducing long-term complications of excess GCs. GC reductions are targeted toward the upper portion of the physiologic range (8-11 mg/m2/day in hydrocortisone equivalents; full range 4-11 mg/m2/day) and are guided primarily by androgen concentrations, with close monitoring for GC withdrawal symptoms and adequate cortisol and mineralocorticoid replacement. Adult patients: The recommendations focus on minimizing GC-related metabolic, cardiovascular and skeletal complications while maintaining androgen control.
GC reductions are targeted toward the physiologic range of 2-14 mg/m2/day in hydrocortisone equivalents and are paced according to current dose to manage any GC withdrawal symptoms and monitor for adequate cortisol replacement. GC reduction can offer important benefits for many patients and is therefore a common treatment goal with CRENESSITY. However, for some patients already taking a physiologic GC dose, CRENESSITY may be initiated to better manage androgens without increasing the GC dose.
Key considerations outlined in both manuscripts include: Dose reductions should be gradual and clinically supervised, with ongoing assessment for symptoms of GC withdrawal, adrenal insufficiency and mineralocorticoid imbalance. Healthcare providers should consider monitoring key biomarkers, which may include androstenedione, 17-hydroxyprogesterone, adrenocorticotropic hormone (ACTH), testosterone and markers of mineralocorticoid status, such as renin and electrolytes. GC dose reduction is not a universal goal; for some patients, the focus is androgens.
The expert recommendation highlights that some individuals may already be receiving a physiologic GC dose and may initiate treatment with CRENESSITY solely for androgen control. Dose reduction should be considered only when appropriate, including when androgens are at or below goal and when clinical goals support reducing supraphysiologic GC exposure.
