Real-World Effectiveness and Safety of Osilodrostat in Cushing’s Syndrome: A Retrospective Phase IV Study

Context: Osilodrostat has demonstrated efficacy in clinical trials for Cushing's syndrome (CS). Real-world data remain limited. Objective: To assess real-world effectiveness and safety of osilodrostat in a large cohort of CS patients. Design&setting: Multicenter, retrospective, phase IV-study across 11 Italian endocrine referral centers. Patients: 100 CS patients [74% pituitary, 16% adrenal, 10% ectopic]. Main outcome measures: Primary endpoint was the percentage of patients with UFC≤ULN at their last observation. Secondary endpoints included biochemical and hormonal control, clinical outcomes, QoL, AEs. Results: 81% of patients had normal UFC levels at last observation, 92% at least once within study period. Excluding 12 patients with normal baseline UFC levels, 78.4% of patients had normal UFC levels at their last observation, whereas 90.9% at least once within the study period.The mean±SD (median,range) time to the first normalization of UFC levels, in the 80 patients who achieved normalization, was 92.1±86.3 (67.5,8-455) days, at a mean± SD (median,range) osilodrostat dose of 7.2±6.8 (5,1-40) mg/day.Significant reductions in late-night salivary cortisol and morning serum cortisol levels were observed. Improvements were noted in anthropometric parameters, blood pressure, glucose metabolism, clinical signs, and QoL. AEs occurred in 29% of patients, mostly mild-to-moderate; adrenal insufficiency was the most common AE reported in 20% of patients. Hormonal control and safety profiles were consistent across CS etiologies. Conclusions: Osilodrostat is effective, generally well tolerated in routine clinical practice, representing a valuable therapy for CS management, able to achieve rapid and sustained hormonal control, significant metabolic, cardiovascular, clinical and QoL improvements with a well-tolerated safety profile.