Treatment effectiveness of pasireotide on health-related quality of life in patients with Cushing's disease.
OBJECTIVE
Cushing's disease (CD) can significantly impair patients' health-related quality of life (HRQOL). This study investigated the 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.


METHODS
In this phase III, randomized, double-blind study, patients with UFC ≥1.5×upper limit of normal (ULN) received s.c. pasireotide 600 or 900 μg 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 Cushing's Quality of Life Questionnaire (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.


METHODS
Pearson's/Spearman's 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, and uncontrolled) at month 6. Analyses were also conducted at month 12, with multivariable adjustment for baseline characteristics and CushingQoL.


RESULTS
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 as follows: 63, 58.8, and 37.9% in the controlled, partially controlled, and uncontrolled groups respectively. Adjusted CushingQoL scores at month 12 were 58.3 for controlled patients (Δ=11.5 vs uncontrolled, P=0.012) and 54.5 for partially controlled patients (Δ=7.7 vs uncontrolled, P=0.170).


CONCLUSIONS
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.
Department of Medicine/EndocrinologyCentre for Biomedical Research on Rare Diseases (CIBERER Unit 747), Hospital Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainDepartment of Quantitative Health SciencesUniversity of Massachusetts Medical School, Worcester, Massachusetts, USAJohn Ware Research GroupInc., Worcester, Massachusetts, USANovartis Pharmaceuticals CorporationEast Hanover, New Jersey, USAAnalysis GroupInc., Boston, Massachusetts, USAIMS HealthBarcelona, SpainRTI Health SolutionsResearch Triangle Park, North Carolina, USANovartis Pharma AGBasel, SwitzerlandDepartment of EndocrinologyCentre for Postgraduate Medical Education, Warsaw, PolandDepartment of EndocrinologyDiabetology and Metabolism, University Hospital, Antwerp, BelgiumNational Institute of Neurology and Neurosurgery 'Manuel Velasco Suárez'Mexico City, MexicoDivision of EndocrinologyMedical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Susan M
SM
Webb
Department of Medicine/EndocrinologyCentre for Biomedical Research on Rare Diseases (CIBERER Unit 747), Hospital Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainDepartment of Quantitative Health SciencesUniversity of Massachusetts Medical School, Worcester, Massachusetts, USAJohn Ware Research GroupInc., Worcester, Massachusetts, USANovartis Pharmaceuticals CorporationEast Hanover, New Jersey, USAAnalysis GroupInc., Boston, Massachusetts, USAIMS HealthBarcelona, SpainRTI Health SolutionsResearch Triangle Park, North Carolina, USANovartis Pharma AGBasel, SwitzerlandDepartment of EndocrinologyCentre for Postgraduate Medical Education, Warsaw, PolandDepartment of EndocrinologyDiabetology and Metabolism, University Hospital, Antwerp, BelgiumNational Institute of Neurology and Neurosurgery 'Manuel Velasco Suárez'Mexico City, MexicoDivision of EndocrinologyMedical School, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilDepartment of Medicine/EndocrinologyCentre for Biomedical Research on Rare Diseases (CIBERER Unit 747), Hospital Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainDepartment of Quantitative Health SciencesUniversity of Massachusetts Medical School, Worcester, Massachusetts, USAJohn Ware Research GroupInc., Worcester, Massachusetts, USANovartis Pharmaceuticals CorporationEast Hanover, New Jersey, USAAnalysis GroupInc., Boston, Massachusetts, USAIMS HealthBarcelona, SpainRTI Health SolutionsResearch Triangle Park, North Carolina, USANovartis Pharma AGBasel, SwitzerlandDepartment of EndocrinologyCentre for Postgraduate Medical Education, Warsaw, PolandDepartment of EndocrinologyDiabetology and Metabolism, University Hospital, Antwerp, BelgiumNational Institute of Neurology and Neurosurgery 'Manuel Velasco Suárez'Mexico City, MexicoDivision of EndocrinologyMedical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
John E
JE
Ware
Department of Medicine/EndocrinologyCentre for Biomedical Research on Rare Diseases (CIBERER Unit 747), Hospital Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainDepartment of Quantitative Health SciencesUniversity of Massachusetts Medical School, Worcester, Massachusetts, USAJohn Ware Research GroupInc., Worcester, Massachusetts, USANovartis Pharmaceuticals CorporationEast Hanover, New Jersey, USAAnalysis GroupInc., Boston, Massachusetts, USAIMS HealthBarcelona, SpainRTI Health SolutionsResearch Triangle Park, North Carolina, USANovartis Pharma AGBasel, SwitzerlandDepartment of EndocrinologyCentre for Postgraduate Medical Education, Warsaw, PolandDepartment of EndocrinologyDiabetology and Metabolism, University Hospital, Antwerp, BelgiumNational Institute of Neurology and Neurosurgery 'Manuel Velasco Suárez'Mexico City, MexicoDivision of EndocrinologyMedical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Anna
A
Forsythe
Department of Medicine/EndocrinologyCentre for Biomedical Research on Rare Diseases (CIBERER Unit 747), Hospital Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainDepartment of Quantitative Health SciencesUniversity of Massachusetts Medical School, Worcester, Massachusetts, USAJohn Ware Research GroupInc., Worcester, Massachusetts, USANovartis Pharmaceuticals CorporationEast Hanover, New Jersey, USAAnalysis GroupInc., Boston, Massachusetts, USAIMS HealthBarcelona, SpainRTI Health SolutionsResearch Triangle Park, North Carolina, USANovartis Pharma AGBasel, SwitzerlandDepartment of EndocrinologyCentre for Postgraduate Medical Education, Warsaw, PolandDepartment of EndocrinologyDiabetology and Metabolism, University Hospital, Antwerp, BelgiumNational Institute of Neurology and Neurosurgery 'Manuel Velasco Suárez'Mexico City, MexicoDivision of EndocrinologyMedical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil myang@analysisgroup.com.
Min
M
Yang
Department of Medicine/EndocrinologyCentre for Biomedical Research on Rare Diseases (CIBERER Unit 747), Hospital Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainDepartment of Quantitative Health SciencesUniversity of Massachusetts Medical School, Worcester, Massachusetts, USAJohn Ware Research GroupInc., Worcester, Massachusetts, USANovartis Pharmaceuticals CorporationEast Hanover, New Jersey, USAAnalysis GroupInc., Boston, Massachusetts, USAIMS HealthBarcelona, SpainRTI Health SolutionsResearch Triangle Park, North Carolina, USANovartis Pharma AGBasel, SwitzerlandDepartment of EndocrinologyCentre for Postgraduate Medical Education, Warsaw, PolandDepartment of EndocrinologyDiabetology and Metabolism, University Hospital, Antwerp, BelgiumNational Institute of Neurology and Neurosurgery 'Manuel Velasco Suárez'Mexico City, MexicoDivision of EndocrinologyMedical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Xavier
X
Badia
Department of Medicine/EndocrinologyCentre for Biomedical Research on Rare Diseases (CIBERER Unit 747), Hospital Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainDepartment of Quantitative Health SciencesUniversity of Massachusetts Medical School, Worcester, Massachusetts, USAJohn Ware Research GroupInc., Worcester, Massachusetts, USANovartis Pharmaceuticals CorporationEast Hanover, New Jersey, USAAnalysis GroupInc., Boston, Massachusetts, USAIMS HealthBarcelona, SpainRTI Health SolutionsResearch Triangle Park, North Carolina, USANovartis Pharma AGBasel, SwitzerlandDepartment of EndocrinologyCentre for Postgraduate Medical Education, Warsaw, PolandDepartment of EndocrinologyDiabetology and Metabolism, University Hospital, Antwerp, BelgiumNational Institute of Neurology and Neurosurgery 'Manuel Velasco Suárez'Mexico City, MexicoDivision of EndocrinologyMedical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Lauren M
LM
Nelson
Department of Medicine/EndocrinologyCentre for Biomedical Research on Rare Diseases (CIBERER Unit 747), Hospital Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainDepartment of Quantitative Health SciencesUniversity of Massachusetts Medical School, Worcester, Massachusetts, USAJohn Ware Research GroupInc., Worcester, Massachusetts, USANovartis Pharmaceuticals CorporationEast Hanover, New Jersey, USAAnalysis GroupInc., Boston, Massachusetts, USAIMS HealthBarcelona, SpainRTI Health SolutionsResearch Triangle Park, North Carolina, USANovartis Pharma AGBasel, SwitzerlandDepartment of EndocrinologyCentre for Postgraduate Medical Education, Warsaw, PolandDepartment of EndocrinologyDiabetology and Metabolism, University Hospital, Antwerp, BelgiumNational Institute of Neurology and Neurosurgery 'Manuel Velasco Suárez'Mexico City, MexicoDivision of EndocrinologyMedical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
James E
JE
Signorovitch
Department of Medicine/EndocrinologyCentre for Biomedical Research on Rare Diseases (CIBERER Unit 747), Hospital Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainDepartment of Quantitative Health SciencesUniversity of Massachusetts Medical School, Worcester, Massachusetts, USAJohn Ware Research GroupInc., Worcester, Massachusetts, USANovartis Pharmaceuticals CorporationEast Hanover, New Jersey, USAAnalysis GroupInc., Boston, Massachusetts, USAIMS HealthBarcelona, SpainRTI Health SolutionsResearch Triangle Park, North Carolina, USANovartis Pharma AGBasel, SwitzerlandDepartment of EndocrinologyCentre for Postgraduate Medical Education, Warsaw, PolandDepartment of EndocrinologyDiabetology and Metabolism, University Hospital, Antwerp, BelgiumNational Institute of Neurology and Neurosurgery 'Manuel Velasco Suárez'Mexico City, MexicoDivision of EndocrinologyMedical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Lori
L
McLeod
Department of Medicine/EndocrinologyCentre for Biomedical Research on Rare Diseases (CIBERER Unit 747), Hospital Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainDepartment of Quantitative Health SciencesUniversity of Massachusetts Medical School, Worcester, Massachusetts, USAJohn Ware Research GroupInc., Worcester, Massachusetts, USANovartis Pharmaceuticals CorporationEast Hanover, New Jersey, USAAnalysis GroupInc., Boston, Massachusetts, USAIMS HealthBarcelona, SpainRTI Health SolutionsResearch Triangle Park, North Carolina, USANovartis Pharma AGBasel, SwitzerlandDepartment of EndocrinologyCentre for Postgraduate Medical Education, Warsaw, PolandDepartment of EndocrinologyDiabetology and Metabolism, University Hospital, Antwerp, BelgiumNational Institute of Neurology and Neurosurgery 'Manuel Velasco Suárez'Mexico City, MexicoDivision of EndocrinologyMedical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Mario
M
Maldonado
Department of Medicine/EndocrinologyCentre for Biomedical Research on Rare Diseases (CIBERER Unit 747), Hospital Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainDepartment of Quantitative Health SciencesUniversity of Massachusetts Medical School, Worcester, Massachusetts, USAJohn Ware Research GroupInc., Worcester, Massachusetts, USANovartis Pharmaceuticals CorporationEast Hanover, New Jersey, USAAnalysis GroupInc., Boston, Massachusetts, USAIMS HealthBarcelona, SpainRTI Health SolutionsResearch Triangle Park, North Carolina, USANovartis Pharma AGBasel, SwitzerlandDepartment of EndocrinologyCentre for Postgraduate Medical Education, Warsaw, PolandDepartment of EndocrinologyDiabetology and Metabolism, University Hospital, Antwerp, BelgiumNational Institute of Neurology and Neurosurgery 'Manuel Velasco Suárez'Mexico City, MexicoDivision of EndocrinologyMedical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Wojciech
W
Zgliczynski
Department of Medicine/EndocrinologyCentre for Biomedical Research on Rare Diseases (CIBERER Unit 747), Hospital Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainDepartment of Quantitative Health SciencesUniversity of Massachusetts Medical School, Worcester, Massachusetts, USAJohn Ware Research GroupInc., Worcester, Massachusetts, USANovartis Pharmaceuticals CorporationEast Hanover, New Jersey, USAAnalysis GroupInc., Boston, Massachusetts, USAIMS HealthBarcelona, SpainRTI Health SolutionsResearch Triangle Park, North Carolina, USANovartis Pharma AGBasel, SwitzerlandDepartment of EndocrinologyCentre for Postgraduate Medical Education, Warsaw, PolandDepartment of EndocrinologyDiabetology and Metabolism, University Hospital, Antwerp, BelgiumNational Institute of Neurology and Neurosurgery 'Manuel Velasco Suárez'Mexico City, MexicoDivision of EndocrinologyMedical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Christophe
C
de Block
Department of Medicine/EndocrinologyCentre for Biomedical Research on Rare Diseases (CIBERER Unit 747), Hospital Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainDepartment of Quantitative Health SciencesUniversity of Massachusetts Medical School, Worcester, Massachusetts, USAJohn Ware Research GroupInc., Worcester, Massachusetts, USANovartis Pharmaceuticals CorporationEast Hanover, New Jersey, USAAnalysis GroupInc., Boston, Massachusetts, USAIMS HealthBarcelona, SpainRTI Health SolutionsResearch Triangle Park, North Carolina, USANovartis Pharma AGBasel, SwitzerlandDepartment of EndocrinologyCentre for Postgraduate Medical Education, Warsaw, PolandDepartment of EndocrinologyDiabetology and Metabolism, University Hospital, Antwerp, BelgiumNational Institute of Neurology and Neurosurgery 'Manuel Velasco Suárez'Mexico City, MexicoDivision of EndocrinologyMedical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Lesly
L
Portocarrero-Ortiz
Department of Medicine/EndocrinologyCentre for Biomedical Research on Rare Diseases (CIBERER Unit 747), Hospital Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainDepartment of Quantitative Health SciencesUniversity of Massachusetts Medical School, Worcester, Massachusetts, USAJohn Ware Research GroupInc., Worcester, Massachusetts, USANovartis Pharmaceuticals CorporationEast Hanover, New Jersey, USAAnalysis GroupInc., Boston, Massachusetts, USAIMS HealthBarcelona, SpainRTI Health SolutionsResearch Triangle Park, North Carolina, USANovartis Pharma AGBasel, SwitzerlandDepartment of EndocrinologyCentre for Postgraduate Medical Education, Warsaw, PolandDepartment of EndocrinologyDiabetology and Metabolism, University Hospital, Antwerp, BelgiumNational Institute of Neurology and Neurosurgery 'Manuel Velasco Suárez'Mexico City, MexicoDivision of EndocrinologyMedical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Monica
M
Gadelha
D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D047748:Pituitary ACTH Hypersecretion / Q000188:drug therapy*; D011788:Quality of Life; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D013004:Somatostatin; C517782:pasireotide