Neurocrine Biosciences published the first peer-reviewed expert recommendations for glucocorticoid dose reduction in classic congenital adrenal hyperplasia patients treated with CRENESSITY, supported by findings from the Phase 3 CAHtalyst Adult (NCT04490915) and Pediatric (NCT04806451) studies.
Written By: Fariha Sameen, PharmD
Reviewed By: Pharmacally Editorial Team
Neurocrine Biosciences announced the publication of the first peer-reviewed expert recommendations for glucocorticoid (GC) dose reduction in patients with classic congenital adrenal hyperplasia (CAH) treated with CRENESSITY. Published in The Journal of Clinical Endocrinology & Metabolism, the recommendations provide clinicians with structured strategies to reduce supraphysiologic GC exposure while maintaining cortisol replacement and androgen control.
The publication includes separate treatment algorithms for pediatric patients aged 4–17 years and adults, representing the first structured approach for GC tapering after CRENESSITY initiation in real-world clinical practice. CRENESSITY received U.S. FDA approval in December 2024 as an adjunct to glucocorticoid replacement therapy for adults and children aged four years and older with classic CAH.
Classic CAH is a rare genetic disorder, most commonly caused by 21-hydroxylase deficiency, that disrupts cortisol and aldosterone production. Patients often require lifelong glucocorticoid therapy. Historically, supraphysiologic GC doses have been used to suppress excess adrenocorticotropic hormone (ACTH) and androgen production, but prolonged exposure has been associated with metabolic, cardiovascular, skeletal, psychological, and cognitive complications.
CRENESSITY is an oral corticotropin-releasing factor type 1 receptor (CRF1) antagonist that lowers ACTH and adrenal androgen production through a non-glucocorticoid mechanism, potentially allowing patients to transition toward more physiologic GC dosing.
Sanjay Keswani, Chief Medical Officer at Neurocrine Biosciences, said the recommendations reflect an important shift in CAH management by helping reduce androgen excess and long-term glucocorticoid burden while preserving essential cortisol replacement.
The pediatric recommendations target hydrocortisone-equivalent doses of 8–11 mg/m²/day to support normal growth, bone maturation, and pubertal development, with close monitoring of androgen levels, cortisol replacement, and withdrawal symptoms. Adult recommendations aim for 2–14 mg/m²/day equivalents and focus on reducing metabolic, cardiovascular, and skeletal complications while maintaining androgen control.
Mimi Kim of the Keck School of Medicine at the University of Southern California said the framework helps clinicians balance disease control with normal growth and development in pediatric patients. Oksana Hamidi of UT Southwestern Medical Center noted that CRENESSITY may help reduce dependence on high glucocorticoid doses for androgen control.
The recommendations emphasize that GC reduction may not be appropriate for all patients, as some may use CRENESSITY primarily for androgen control. Dose adjustments should remain gradual and clinically supervised, with monitoring of adrenal insufficiency, mineralocorticoid status, androstenedione, ACTH, testosterone, renin, and electrolytes.
The guidance builds on findings from the Phase 3 CAHtalyst Adult (NCT04490915) and CAHtalyst Pediatric (NCT04806451) studies, which enrolled a combined 285 patients with classic CAH. The trials showed that CRENESSITY improved androgen control while enabling glucocorticoid dose reductions, with ongoing open-label extension studies continuing to evaluate long-term outcomes.
References
Natalie J Nokoff et al, Glucocorticoid Reduction After Starting Crinecerfont in Pediatric Patients With Classic CAH: Practical Perspectives, The Journal of Clinical Endocrinology & Metabolism, 2026;, dgag192, https://doi.org/10.1210/clinem/dgag192
Oksana Hamidi et al, Glucocorticoid reduction after starting crinecerfont in adult patients with classic CAH: practical perspectives, The Journal of Clinical Endocrinology & Metabolism, 2026;, dgag147, https://doi.org/10.1210/clinem/dgag147
About the Writer
Fariha Sameen, PharmD, is a clinical pharmacy professional with hands-on experience in patient counselling, medication review, therapeutic monitoring, and clinical documentation across multiple departments. She has experience identifying and assessing drug-related problems and supporting medication safety practices. Her interests include pharmacovigilance, ADR reporting, clinical research, and medical writing focused on clear, evidence-based communication.