SAT-206 - Crinecerfont Improved Biochemical Control in All Treated Patients with Congenital Adrenal Hyperplasia in Our Cohort, While the Possibility of Dose Reduction Depended on Baseline Control.

Background:
Many patients with classical congenital adrenal hyperplasia (CAH) fail to achieve adequate biochemical control despite high-dose glucocorticoid (GC) therapy. Crinecerfont, a CRF1 antagonist, suppresses ACTH-driven adrenal steroid production of 17-hydroxyprogesterone (17OHP), Androstenedione (A4), and testosterone, enabling improved disease control and reduced supraphysiologic GC dosing.

Methods:
We retrospectively reviewed the medical records of 15 patients with CAH (11 salt-wasting, 4 simple virilizing; 11 males, 4 females), aged 13 ± 4.8 years (range: 7–22 years), including one 48-year-old adult, who were treated with Crinecerfont. Patients were stratified by baseline biochemical control: good (17-OHP < 1000 ng/dL, A4 < 200 ng/dL; n=4), moderate (17-OHP 1000–4000 ng/dL, A4 < 450 ng/dL; n=5), and poor (17-OHP >8000 ng/dL, A4 >600 ng/dL; n=6). Hormonal profiles and GC dosing (mg/m²) were followed longitudinally.

Results:
All 4 patients in the good-control group achieved complete normalization of steroid profiles after Crinecerfont initiation and maintained good control after GC dose reduction. After Crinecerfont started 17 OHP decreased from 289.8 ± 222.2 to 102.3 ± 52.0, A4 from 45 ± 37.8 to 23.7 ± 16.7. After dose reduction by 26 ± 11%, 17 OHP was 452.5 ± 416.6, A4 43.25 ± 31.72.
All 5 patients in the moderate-control group achieved complete normalization of steroid profiles after Crinecerfont initiation, and four maintained good control after GC dose reduction. After Crinecerfont started, 17 OHP decreased from 2945 ± 1625 to 121 ± 164, A4 from 233 ± 247 to 99.8 ± 100. After dose reduction by 18 ± 2.2%, in 4 patients, 17 OHP was 397 ± 341, A4 62 ± 79.9. In one patient, a GC dose reduction from 12 to 10.5 mg/m2 led to biochemical deterioration, and the baseline dose was resumed
All 6 patients in the poor-control group improved their biochemical profiles after Crinecerfont initiation; 17 OHP decreased from 15079 ± 13949 to 2933 ± 2547, A4 from 857 ± 728 to 202 ± 168.6. Two achieved complete normalization, and 4 demonstrated marked biochemical improvement. In 1 case, reducing the GC dose from 13 to 12.5 mg/m² resulted in biochemical deterioration; in 2 other cases, the dose was not reduced, but the hormonal profile normalized after an additional 6 months of follow-up.

Conclusion:
Crinecerfont. improved biochemical control in all patients with classical CAH in our cohort. Crinecerfont enabled normalization of biochemical control and clinically meaningful glucocorticoid dose reductions in patients with good and moderate baseline disease control. Patients with poor baseline control demonstrated substantial biochemical improvement without a possibility of GC dose reduction. The therapy was well tolerated, with no complications observed.

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