Treatment effectiveness of pasireotide on health-related quality of life in patients with Cushing's disease
Webb, S., Ware, JE., Forsythe, A., Yang, M., Badia, X., Nelson, L., Signorovitch, JE., McLeod, L., Maldonado, M., Zgliczynski, W., De Block, C., Portocarrero-Ortiz, L., & Gadelha, MR. (2014). Treatment effectiveness of pasireotide on health-related quality of life in patients with Cushing's disease. European Journal of Endocrinology, 171(1), 89-98. https://doi.org/10.1530/EJE-13-1013
Cushing's disease (CD) can significantly impair patients' health-related quality of life (HRQOL). This study investigated treatment effectiveness of pasireotide on HRQOL of CD patients, and assessed the relationships between HRQOL and urinary free cortisol (UFC) and CD-related signs and symptoms.
In this phase III, randomized, double-blind study, patients with UFC?1.5xUpper Limit of Normal (ULN) received subcutaneous pasireotide 600?g or 900?g twice daily. The trial primary endpoint was UFC at or below ULN at Month 6 without dose titration. Open-label treatment continued through Month 12. HRQOL was measured using the CushingQoL instrument at baseline and follow-up visits until Month 12 during which clinical signs and features of CD, and the Beck Depression Inventory II (BDI-II) were also collected.
Pearson/Spearman correlations between changes in CushingQoL and changes in clinical signs and symptoms were assessed. Changes in CushingQoL, and the proportion of patients achieving a clinically meaningful improvement in CushingQoL, were also compared among patients stratified by mean UFC (mUFC) control status (controlled, partially controlled, uncontrolled) at Month 6. Analyses were also conducted at Month 12, with multivariable adjustment for baseline characteristics and CushingQoL.
Change in CushingQoL was significantly correlated with changes in mUFC (r=-0.40), BMI (r=-0.39), weight (r=-0.41), and BDI-II (r=-0.54) at Month 12 but not at Month 6. The percentage of CushingQoL responders at Month 12 based on Month 6 mUFC control status were: 63%, 58.8%, 37.9% in the controlled, partially controlled, and uncontrolled groups, respectively. Adjusted CushingQoL scores at Month 12 were 58.3 for controlled patients (?=11.5 vs. uncontrolled, p=0.012) and 54.5 for partially controlled patients (?=7.7 vs. uncontrolled, p=0.170).
Pasireotide treatment can result in a meaningful HRQOL improvement among those who complete a 12 month treatment period, most often among patients achieving biochemical control.