SUN-423 Efficacy of Crinecerfont in Reducing Androgen Levels in Congenital Adrenal Hyperplasia: A Meta-Analysis of Randomized Trials

Abstract Disclosure: I. Ismail: None. T. Hodrob: None. A. Abusalameh: None. C.R. Andonie: None. H. Ayesh: None. Introduction: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency disrupts cortisol and aldosterone synthesis, leading to excess androgen production. Current treatment relies on glucocorticoids to suppress ACTH-driven androgen excess, often necessitating supraphysiologic doses that pose significant side effects. Crinecerfont, a non-steroidal CRF1 receptor antagonist, offers a novel approach to reducing 17-hydroxyprogesterone (17OHP) and androstenedione levels, potentially minimizing the need for high-dose glucocorticoid therapy. This meta-analysis evaluates Crinecerfont's efficacy and safety in managing androgen levels in CAH. Methods: A systematic review identified six randomized controlled trials, of which four met inclusion criteria. Random-effects meta-analysis was conducted to assess Crinecerfont's impact on 17OHP and androstenedione levels in pediatric and adult subgroups. Heterogeneity was evaluated using the I² statistic and subgroup analyses. Results: Crinecerfont significantly reduced 17OHP levels (MD: -5729.44 ng/dL, 95% CI: [-6627.85; -4831.03], p < 0.0001) with no evidence of heterogeneity (I² = 0%). Subgroup analysis showed consistent reductions in pediatrics (MD: -5828.39 ng/dL, 95% CI: [-7245.60; -4411.17]) and adults (MD: -5415.82 ng/dL, 95% CI: [-7423.30; -3408.34]). Androstenedione levels were also significantly decreased (MD: -211.33 ng/dL, 95% CI: [-295.49; -127.16], p < 0.0001) with moderate heterogeneity (I² = 44.6%). Reductions were greater in adults (MD: -273.68 ng/dL, 95% CI: [-365.63; -181.73]) than in pediatrics (MD: -155.13 ng/dL, 95% CI: [-244.93; -65.34]). Conclusion: Crinecerfont effectively reduces 17OHP and androstenedione levels in both pediatric and adult CAH populations, offering a promising therapeutic strategy to minimize reliance on high-dose glucocorticoids. Further trials are warranted to confirm long-term efficacy and safety. Presentation: Sunday, July 13, 2025