A Lacroix1, M D Bronstein2, J Schopohl3, T Delibasi4, R Salvatori5, Y Li6, A Barkan7, N Suzaki8, L Tauchmanova9, C-E Ortmann9, S Ravichandran10, S Petersenn11, R Pivonello12. 1. Centre hospitalier de l'Université de Montréal, 3840 Saint-Urbain, Montreal, H2W1T8, Canada. andre.lacroix@umontreal.ca. 2. University of São Paulo Medical School, São Paulo, Brazil. 3. Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany. 4. Hacettepe University, Ankara, Turkey. 5. Division of Endocrinology, Diabetes and Metabolism, and Pituitary Center, Johns Hopkins University, Baltimore, MD, USA. 6. Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China. 7. University of Michigan, Ann Arbor, MI, USA. 8. Nagoya Medical Center, National Hospital Organization, Nagoya, Japan. 9. Novartis Pharma AG, Basel, Switzerland. 10. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. 11. ENDOC Center for Endocrine Tumors, Hamburg, Germany. 12. Università Federico II di Napoli, Naples, Italy.
Abstract
PURPOSE:Cushing's disease (CD) is associated with significant clinical burden, increased mortality risk, and impaired health-related quality of life (HRQoL). This analysis explored the effect of long-acting pasireotide on clinical signs of hypercortisolism and HRQoL in a large subset of patients with CD. METHODS: In this phase III study (clinicaltrials.gov: NCT01374906), 150 adults with CD and a mean urinary free cortisol (mUFC) level between 1.5 and 5.0 times the upper limit of normal (ULN) started long-acting pasireotide 10 or 30 mg every 28 days with dose increases/decreases permitted based on mUFC levels/tolerability (minimum/maximum dose: 5/40 mg). Changes in clinical signs of hypercortisolism and HRQoL were assessed over 12 months of treatment and were stratified by degree of mUFC control for each patient. RESULTS:Patients with controlled mUFC at month 12 (n = 45) had the greatest improvements from baseline in mean systolic (- 8.4 mmHg [95% CI - 13.9, - 2.9]) and diastolic blood pressure (- 6.0 mmHg [- 10.0, - 2.0]). Mean BMI, weight, and waist circumference improved irrespective of mUFC control. Significant improvements in CushingQoL total score of 5.9-8.3 points were found at month 12 compared with baseline, irrespective of mUFC control; changes were driven by improvements in physical problem score, with smaller improvements in psychosocial score. CONCLUSIONS:Long-acting pasireotide provided significant improvements in clinical signs and HRQoL over 12 months of treatment, which, in some cases, occurred regardless of mUFC control. Long-acting pasireotide represents an effective treatment option and provides clinical benefit in patients with CD. CLINICAL TRIAL REGISTRATION NUMBER: NCT01374906.
RCT Entities:
PURPOSE:Cushing's disease (CD) is associated with significant clinical burden, increased mortality risk, and impaired health-related quality of life (HRQoL). This analysis explored the effect of long-acting pasireotide on clinical signs of hypercortisolism and HRQoL in a large subset of patients with CD. METHODS: In this phase III study (clinicaltrials.gov: NCT01374906), 150 adults with CD and a mean urinary free cortisol (mUFC) level between 1.5 and 5.0 times the upper limit of normal (ULN) started long-acting pasireotide 10 or 30 mg every 28 days with dose increases/decreases permitted based on mUFC levels/tolerability (minimum/maximum dose: 5/40 mg). Changes in clinical signs of hypercortisolism and HRQoL were assessed over 12 months of treatment and were stratified by degree of mUFC control for each patient. RESULTS:Patients with controlled mUFC at month 12 (n = 45) had the greatest improvements from baseline in mean systolic (- 8.4 mmHg [95% CI - 13.9, - 2.9]) and diastolic blood pressure (- 6.0 mmHg [- 10.0, - 2.0]). Mean BMI, weight, and waist circumference improved irrespective of mUFC control. Significant improvements in CushingQoL total score of 5.9-8.3 points were found at month 12 compared with baseline, irrespective of mUFC control; changes were driven by improvements in physical problem score, with smaller improvements in psychosocial score. CONCLUSIONS: Long-acting pasireotide provided significant improvements in clinical signs and HRQoL over 12 months of treatment, which, in some cases, occurred regardless of mUFC control. Long-acting pasireotide represents an effective treatment option and provides clinical benefit in patients with CD. CLINICAL TRIAL REGISTRATION NUMBER: NCT01374906.
Entities:
Keywords:
Cushing’s disease; Health-related quality of life; Hypercortisolism; Pasireotide
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