Individualized osilodrostat treatment for patients with ACTH-dependent Cushing's syndrome: real-world evidence

Osilodrostat is an 11β-hydroxylase inhibitor that has demonstrated high efficacy in Cushing's syndrome (CS) in clinical trials; however, real-world data remain limited.

To evaluate dosing patterns, effectiveness, and safety of osilodrostat in patients with adrenocorticotropic hormone (ACTH)-dependent CS.

This retrospective analysis included 26 adults with ACTH-dependent CS (15 with Cushing's disease [CD] and 11 with ectopic CS [ECS]) treated with osilodrostat between 2020 and 2025.

Osilodrostat was introduced as first-line therapy in 12 of 26 patients. A titration regimen was used in 21 patients, and a block-and-replace approach in five. A therapeutic effect was achieved in 92% at a median dose of 5 mg/day (4.5 mg/day in CD and 6.5 mg/day in ECS) within 14 days. Morning cortisol normalized in 92% of cases, and urinary free cortisol in 75%. The median clinical score decreased from 9 to 4, and muscle strength increased from 50% to 75% of normal. All 22 patients requiring potassium supplementation showed improvement, with a median time to dose reduction of 10 days. Systolic/diastolic blood pressure decreased from 142/87 to 124/70 mmHg, enabling reduction of antihypertensive therapy in 22 of 23 patients. Among 20 patients with diabetes, 18 reduced the number or dose of antidiabetic medications, including insulin. Adverse events were mild to moderate and included fatigue and nausea (34.6% each), adrenal insufficiency (30.8%), and dizziness (23.1%).

In real-world clinical practice, osilodrostat provided rapid and effective biochemical control and clinical improvement in ACTH-dependent CS, with a manageable safety profile and effective doses in the low-to-moderate range.