Impact of Osilodrostat on Health-Related Quality of Life in Cushing's Disease: Analysis of Patient-Reported Outcomes From the Phase III LINC 3 and LINC 4 Clinical Trials.

OBJECTIVE

Evaluate the effects of osilodrostat short- and long-term treatment on health-related quality of life (HRQoL) in Cushing's disease.

DESIGN

LINC 3 and LINC 4 studies (pooled analysis).

PATIENTS: 185 patients (mean baseline total scores: Cushing's Quality of Life [CushingQoL], 44.0; Beck Depression Inventory II [BDI-II], 15.6; EuroQol Five Dimensions Five Levels [EQ--5D-5L], 0.7).

MEASUREMENTS: Changes from baseline in CushingQoL, BDI--II and EQ-5D-5L scores. CushingQoL and EuroQol Five Dimensions Three Levels (EQ-5D-3L) scores were assessed in analyses of hypocortisolism-related adverse events (HAEs).

RESULTS

Mean CushingQoL score improved (all p < 0.001) by +7.72 (Week [W]12), +11.45 (W26; achieving minimal clinically important difference [MCID]) and +15.32 (W72). Mean BDI-II score improved (all p < 0.001) by -19.0% (W12; achieving MCID) and -41.2% (W72). EQ-5D-5L utility score improved over W26-72 (p < 0.01), reaching the MCID range at W26. All items/domains in the HRQoL questionnaires significantly improved over time (p < 0.001; ordinal mixed-effects regression), except one BDI-II item (past failure) and one EQ-5D-5L domain (self-care). CushingQoL total score improved in patients with mild (mean urinary free cortisol [mUFC] ≤ 2x upper limit of normal [ULN]), moderate (mUFC > 2-5 × ULN) and severe (mUFC > 5 × ULN) hypercortisolism. BDI-II and EQ-5D-5L total scores improved in patients with moderate and severe hypercortisolism. Grade 3 HAEs temporarily reduced CushingQoL and EQ-5D-3L scores during event weeks. In the multivariable models, longer treatment duration was associated with CushingQoL improvements; higher mUFC, higher body mass index, and occurrence of HAEs were associated with lower CushingQoL scores.

CONCLUSIONS

Osilodrostat improved HRQoL, with clinically meaningful, consistent improvements across HRQoL assessments.