Osilodrostat Treatment of Cushing Syndrome in Real-World Clinical Practice: Findings From the ILLUSTRATE study

In clinical trials, osilodrostat (11β-hydroxylase inhibitor) effectively reduced cortisol levels in patients with endogenous Cushing syndrome (CS).

A real-world study (ILLUSTRATE) was conducted evaluating osilodrostat use in patients with various etiologies of CS in the United States.

A retrospective chart-review study was conducted of adults with CS treated with osilodrostat between May 1, 2020, and October 29, 2021.

A total of 42 patients (Cushing disease, n = 34; CS due to adrenal adenoma, n = 5; ectopic adrenocorticotropin syndrome [EAS], n = 3) were included. Starting doses were 2 mg twice daily in 27/42 patients (64.3%), maintenance doses were 2 mg twice daily in 6 of 9 patients (66.7%) attaining them. During osilodrostat treatment, urinary free cortisol (UFC) decreased below the upper limit of normal (ULN) in 14 of 20 patients (70.0%) with pretreatment UFC greater than the ULN. Osilodrostat response was observed across a range of doses (2-20 mg/day). In Cushing disease, median UFC and late-night salivary cortisol decreased from 3.03 and 2.39 × ULN, respectively, to 0.71 and 1.13 × ULN at last assessment in those with available data (n = 17 and 8, respectively). UFC decreased in all patients with adrenal CS or EAS with available data (n = 2 each). There were no unexpected safety signals; the most common adverse events (incidence ≥20%) were fatigue, nausea, and lower-extremity edema. Glucocorticoid withdrawal syndrome and/or adrenal insufficiency were reported in 12 of 42 patients (28.6%) after osilodrostat initiation, resulting in treatment discontinuation in 4.

In routine practice with dosing individualized according to clinical condition, response, and tolerability, osilodrostat was effective and well tolerated regardless of CS etiology and severity.