Health-Related Quality of Life of Patients With Cushing’s Disease Treated With Osilodrostat: Mixed-Effects Regression Analysis

OBJECTIVES: Cushing’s disease (CD) is a rare endocrine disorder characterized by cortisol overproduction. According to the international clinical guidelines the primary treatment goal is to normalize cortisol concentrations (biochemical control), which may lead to improvements in Health-Related Quality of Life (HRQoL).

The objective is to estimate the Health Utility Values (HUV) in biochemically controlled and uncontrolled patients with possible use in a cost-effectiveness evaluation.

METHODS: EQ-5D values, which are the preferred utility measure of health states, were available in the phase III studies of osilodrostat, LINC-3 and LINC-4. Multiple linear mixed-effects regression models were fitted to assess patients’ HRQoL, considering the longitudinal cohort type of the data. Models considered various combinations of the potentially relevant covariates e.g. age, sex, BMI, hypocortisolism-related adverse events (AEs), duration of cortisol normalization and mean urinary free cortisol (mUFC) value. The final model was selected based on the Information Criterion.

RESULTS: 209 Cushing’s disease patients were available, with a maximum observation of 245 weeks. The regression model showed that BMI, mUFC, grade 3+ hypocortisolism-related AEs and the duration of cortisol normalization were prognostic factors of the utility values (p<0.05).

The estimated utility value for uncontrolled patients was 0.696. For controlled patients the utility value depended on the time spent in a controlled state and was estimated to be 0.762 and 0.825 respectively, at 96 and 204 weeks of treatment. As 97% of patients were controlled at least once during the studies’ duration, it was not possible to model utility value for the uncontrolled patients in time.

CONCLUSIONS: There is a significant difference in HUVs between biochemically controlled and uncontrolled CS patients. HRQoL improves with mUFC reduction and lower BMI and declines with hypocortisolism-related AEs. HRQoL also increases with the duration of cortisol normalization suggesting CS patients can recover with effective biochemical control.