PMID- 31379734
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200414
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 10
DP  - 2019
TI  - Safety and Efficacy of Subcutaneous Pasireotide in Patients With Cushing's 
      Disease: Results From an Open-Label, Multicenter, Single-Arm, Multinational, 
      Expanded-Access Study.
PG  - 436
LID - 10.3389/fendo.2019.00436 [doi]
LID - 436
AB  - Introduction: The efficacy and safety of subcutaneous (sc) pasireotide have been 
      evaluated in a Phase III trial. Here, we report safety and efficacy results from 
      a multinational, expanded-access study of pasireotide sc in patients with 
      Cushing's disease (CD) in a real-world setting (clinicaltrials.gov, identifier: 
      NCT01582061). Methods: Adults with active CD previously untreated with 
      pasireotide were enrolled; pasireotide sc was initiated at 600 mug twice daily 
      (bid; EU countries) or 900 mug bid (non-EU countries; 600 mug bid in patients with 
      impaired glucose metabolism). Pasireotide dose could be adjusted in 300 mug 
      increments/decrements to a maximum of 900 mug bid or minimum of 300 mug bid for 
      sustained urinary free cortisol (UFC) normalization/tolerability issues. Primary 
      objective: document the safety of pasireotide sc in patients with CD. Key 
      secondary objectives: assess the proportion of patients with mean UFC (mUFC) not 
      exceeding the upper limit of normal (ULN) and changes from baseline in clinical 
      signs/symptoms and quality of life (QoL) to weeks 12, 24, and 48. Results: One 
      hundred and four patients received pasireotide: female, n = 84 (80.8%); median 
      duration of pasireotide exposure, 25.1 weeks; median (range) baseline mUFC, 321.2 
      nmol/24 h (142-10,920; 2.3 x ULN [1.0-79.2]). Forty (38.5%) patients completed 
      the study. The most common reasons for premature discontinuation of pasireotide 
      were unsatisfactory therapeutic effect (n = 26, 25.0%) and adverse events (AEs; n 
      = 20, 19.2%). Drug-related grade 3/4 AEs or drug-related serious AEs (primary 
      endpoint) were documented in 42 (40.4%) patients, most commonly diabetes mellitus 
      (n = 12, 11.5%) and hyperglycemia (n = 8, 7.7%). All patients experienced >/=1 AE 
      and most (n = 102; 98.1%) reported >/=1 drug-related AE; six (5.8%) patients 
      discontinued treatment because of hyperglycemia-related AEs. At weeks 12, 24, and 
      48, respectively, 36/66 (54.5%), 22/46 (47.8%), and 9/21 (42.9%) evaluable 
      patients had normalized mUFC levels. Clinical signs/symptoms and QoL were also 
      improved. Conclusions: In an international, real-world, clinical-practice 
      setting, pasireotide sc was generally well-tolerated (no new safety signals were 
      identified), effectively reduced UFC (normalization in ~50% of evaluable 
      patients) and improved clinical signs and QoL in patients with CD. While 
      hyperglycemia-related AEs were common, consistent with previous studies, most 
      were manageable, with <6% of patients discontinuing treatment because of these 
      events.
FAU - Fleseriu, Maria
AU  - Fleseriu M
AD  - Departments of Medicine and Neurological Surgery, Northwest Pituitary Center, 
      Oregon Health and Science University, Portland, OR, United States.
FAU - Iweha, Chioma
AU  - Iweha C
AD  - Panda Medical Associates, Peoria, AZ, United States.
FAU - Salgado, Luiz
AU  - Salgado L
AD  - General Internal Medicine Service, Hospital das Clinicas da Faculdade de Medicina 
      FMUSP, Sao Paulo, Brazil.
FAU - Mazzuco, Tania Longo
AU  - Mazzuco TL
AD  - Division of Endocrinology of Medical Clinical Department, University Hospital, 
      UEL, Londrina, Brazil.
FAU - Campigotto, Federico
AU  - Campigotto F
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States.
FAU - Maamari, Ricardo
AU  - Maamari R
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States.
FAU - Limumpornpetch, Padiporn
AU  - Limumpornpetch P
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand.
LA  - eng
SI  - ClinicalTrials.gov/NCT01582061
GR  - UL1 TR002369/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20190716
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
PMC - PMC6646464
OTO - NOTNLM
OT  - Cushing's disease
OT  - clinical practice
OT  - pasireotide sc
OT  - real world
OT  - somatostatin analog
EDAT- 2019/08/06 06:00
MHDA- 2019/08/06 06:01
PMCR- 2019/01/01
CRDT- 2019/08/06 06:00
PHST- 2019/03/05 00:00 [received]
PHST- 2019/06/18 00:00 [accepted]
PHST- 2019/08/06 06:00 [entrez]
PHST- 2019/08/06 06:00 [pubmed]
PHST- 2019/08/06 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2019.00436 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2019 Jul 16;10:436. doi: 10.3389/fendo.2019.00436. 
      eCollection 2019.