The Impact of Glucocorticoid (GC) Dose on Clinical Outcomes in Congenital Adrenal Hyperplasia (CAH): A Systematic Literature Review (SLR)
Author(s)
Hyunwoo Kim, PharmD, MS1, Henry Cheng, MA, MS, PhD1, Brian Leinwand, PhD2, Mary Mulrooney, PharmD, MBA2, Vivian H. Lin, MD1, Sonia Acosta Luis, MSc2, Conor Maher, MBiochem2, Irina Bancos, MD, MSc3.
1Neurocrine Biosciences, Inc, San Diego, CA, USA, 2Trinity Life Sciences, Waltham, MA, USA, 3Mayo Clinic, Rochester, MN, USA.
1Neurocrine Biosciences, Inc, San Diego, CA, USA, 2Trinity Life Sciences, Waltham, MA, USA, 3Mayo Clinic, Rochester, MN, USA.
Presentation Documents
OBJECTIVES: CAH is a rare condition associated with hyperandrogenism and cortisol deficiency, historically requiring reliance on lifelong supraphysiologic GCs to address both hyperandrogenism and cortisol deficiency. Consequently, patients with CAH are at higher risk of GC-associated complications across cardiometabolic, bone, growth, and other domains. However, as the relationship between GC dose and adverse clinical outcomes in CAH has not been fully synthesized in prior literature, the purpose of this SLR was to comprehensively characterize the relationship between GC dose and clinical outcomes.
METHODS: An SLR was conducted using PubMed and Embase, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Since CAH is a rare condition, we included additional endocrine and other disorders with GC exposures of similar magnitude as CAH (ie, Addison’s disease, adrenal insufficiency, hypopituitarism, polymyalgia rheumatica, and mild autonomous cortisol secretion) to ensure ample evidence was reviewed.
RESULTS: Of 2,077 unique publications identified, 106 met inclusion criteria. Of these, most (63%) included patients with CAH. Across these 106 publications, 547 clinical outcomes were reported (354 in adults, 161 in children, 32 in both): 34% related to bone health, 27% cardiometabolic, and 13% height/growth. 62% of publications (n=66/106) reported statistically significant relationships between clinical outcomes and GC dose; 95% of those (n=63/66) concluded higher GC dose was statistically significantly associated with adverse clinical outcomes, including decreased bone mineral density, increased insulin resistance, and higher body mass index. The remaining 38% of publications (n=40/106) reported relationships between GC dose and clinical outcomes that did not reach statistical significance.
CONCLUSIONS: This SLR underscores the profound clinical burden patients with CAH face due to long-term use of supraphysiologic GC doses and challenges faced by clinicians to optimize treatment. Novel non-glucocorticoid treatment options for CAH, the first of which was approved 12/2024, support reduced GC doses, which may reduce the incidence of associated complications.
METHODS: An SLR was conducted using PubMed and Embase, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Since CAH is a rare condition, we included additional endocrine and other disorders with GC exposures of similar magnitude as CAH (ie, Addison’s disease, adrenal insufficiency, hypopituitarism, polymyalgia rheumatica, and mild autonomous cortisol secretion) to ensure ample evidence was reviewed.
RESULTS: Of 2,077 unique publications identified, 106 met inclusion criteria. Of these, most (63%) included patients with CAH. Across these 106 publications, 547 clinical outcomes were reported (354 in adults, 161 in children, 32 in both): 34% related to bone health, 27% cardiometabolic, and 13% height/growth. 62% of publications (n=66/106) reported statistically significant relationships between clinical outcomes and GC dose; 95% of those (n=63/66) concluded higher GC dose was statistically significantly associated with adverse clinical outcomes, including decreased bone mineral density, increased insulin resistance, and higher body mass index. The remaining 38% of publications (n=40/106) reported relationships between GC dose and clinical outcomes that did not reach statistical significance.
CONCLUSIONS: This SLR underscores the profound clinical burden patients with CAH face due to long-term use of supraphysiologic GC doses and challenges faced by clinicians to optimize treatment. Novel non-glucocorticoid treatment options for CAH, the first of which was approved 12/2024, support reduced GC doses, which may reduce the incidence of associated complications.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO16
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Diabetes/Endocrine/Metabolic Disorders (including obesity)