Real-world data on the efficacy and safety of osilodrostat in patients with Cushing's disease in Spain

Abstract

[Abstract] Objective: To evaluate the efficacy and safety of osilodrostat in patients with Cushing's disease (CD). Methods: A retrospective, multicenter, real-world study of patients with CD. The main efficacy endpoint was the proportion of patients who were complete responders (urinary free cortisol [UFC] < the upper limit of normal and/or with adrenal insufficiency development). Results: Thirty-seven CD patients were enrolled. There were 33 patients who initially received osilodrostat in monotherapy and 4 in combination. However, 3 patients of the monotherapy group were switched to combination therapy. The median duration of osilodrostat treatment was 5 months (range 1-93). All the patients were classified as responders: 33 (89.2%) had complete response and 4 partial response. A positive correlation was detected between the percentage of UFC decrease and the maximum (r = 0.481, p = 0.006) and the maintenance doses (r = 0.440, p = 0.011). The initial doses of osilodrostat were a predictor of complete response (vs. partial) (Odds ratio [OR] 2.82, p = 0.030). The median time to UFC normalization in the group of complete responders was 4 weeks (range 1-20) and UFC normalized before or at month 1 in 67% (n = 20/30) of the patients. Osilodrostat led to a significant decrease in systolic and diastolic blood pressure in parallel with a reduction of antihypertensive medications. Conclusions: Osilodrostat leads to a complete UFC normalization in up to 90% of the patients with CD, in parallel with an improvement in the cardiometabolic profile. A proper titration of osilodrostat is important to achieve a complete response since a positive correlation between the doses and the UFC reduction was observed.