PMID- 25776130
OWN - NLM
STAT- MEDLINE
DCOM- 20150901
LR  - 20161125
IS  - 1096-8652 (Electronic)
IS  - 0361-8609 (Linking)
VI  - 90
IP  - 7
DP  - 2015 Jul
TI  - Safety and efficacy results of switch from imiglucerase to velaglucerase alfa 
      treatment in patients with type 1 Gaucher disease.
PG  - 592-7
LID - 10.1002/ajh.24007 [doi]
AB  - Gaucher disease (GD) is a lysosomal storage disorder; symptomatic patients with 
      type 1 GD need long-term disease-specific therapy of which the standard of care 
      has been enzyme replacement therapy (ERT). Thirty-eight of 40 patients (aged 9-71 
      years) clinically stable on ERT with imiglucerase, safely switched to a 
      comparable dose of velaglucerase alfa (units/kg) during TKT034, a 12-month, 
      open-label clinical study, and for 10-50 months in an extension study. The most 
      common adverse events (AEs) judged to be drug-related in the extension were 
      fatigue and bone pain. No drug-related serious AEs were reported. No AEs led to 
      study withdrawal. At 24 months from baseline (baseline being TKT034 week 0), 
      patients had generally stable hemoglobin, platelet, spleen, liver, and bone 
      density parameters. Nevertheless, dose adjustment based on the achievement of 
      therapeutic goals was permitted, and 10 patients, including seven patients who 
      had platelet counts <100 x 10(9) /L at baseline, were given at least one 15 
      U/kg-dose increase during the extension. Trends indicative of improvement in 
      platelet count and spleen volume, and decreasing levels of GD biomarkers, 
      chitotriosidase and CCL18, were observed. Immunogenicity was seen in one patient 
      positive for anti-imiglucerase antibodies at baseline. This patient tested 
      positive for anti-velaglucerase alfa antibodies in TKT034, with low antibody 
      concentrations, and throughout the extension study; however, the patient 
      continued to receive velaglucerase alfa without clinical deterioration. In 
      conclusion, clinically stable patients can be switched from imiglucerase to 
      velaglucerase alfa ERT and maintain or achieve good therapeutic outcomes.
CI  - (c) 2015 The Authors. American Journal of Hematology published by Wiley 
      Periodicals, Inc.
FAU - Elstein, Deborah
AU  - Elstein D
AD  - Gaucher Clinic, Shaare Zedek Medical Center, affiliated with the Hebrew 
      University-Hadassah Medical School, Jerusalem, Israel.
FAU - Mehta, Atul
AU  - Mehta A
AD  - Department of Haematology, Royal Free Hospital, London, United Kingdom.
AD  - Department of Haematology, University College London, London, United Kingdom.
FAU - Hughes, Derralynn A
AU  - Hughes DA
AD  - Department of Haematology, Royal Free Hospital, London, United Kingdom.
AD  - Department of Haematology, University College London, London, United Kingdom.
FAU - Giraldo, Pilar
AU  - Giraldo P
AD  - Medicina Metabolica Hereditaria, Centro de Investigacion Biomedica en Red de 
      Enfermedades Raras (CIBERER), Zaragoza, Spain.
AD  - Grupo de Estudio de Enfermedades Hematologicas y Metabolicas, Hospital 
      Universitario Miguel Servet, Zaragoza, Spain.
FAU - Charrow, Joel
AU  - Charrow J
AD  - Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, 
      Chicago, Illinois.
FAU - Smith, Laurie
AU  - Smith L
AD  - Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, 
      Missouri.
FAU - Shankar, Suma P
AU  - Shankar SP
AD  - Departments of Human Genetics and Ophthalmology, School of Medicine, Emory 
      University, Atlanta, Georgia.
FAU - Hangartner, Thomas N
AU  - Hangartner TN
AD  - Department of Biomedical, Industrial, & Human Factors Engineering, Wright State 
      University, Dayton, Ohio.
FAU - Kunes, Yune
AU  - Kunes Y
AD  - Bioanalytical and BioMarker Development, Shire, Lexington, Massachusetts.
FAU - Wang, Nan
AU  - Wang N
AD  - Biostatistics & Statistical Programming Department, Shire, Lexington, 
      Massachusetts.
FAU - Crombez, Eric
AU  - Crombez E
AD  - Rare Disease Unit, Shire, Lexington, Massachusetts.
FAU - Zimran, Ari
AU  - Zimran A
AD  - Gaucher Clinic, Shaare Zedek Medical Center, affiliated with the Hebrew 
      University-Hadassah Medical School, Jerusalem, Israel.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hematol
JT  - American journal of hematology
JID - 7610369
RN  - 0 (CCL18 protein, human)
RN  - 0 (Chemokines, CC)
RN  - 0 (Hemoglobins)
RN  - 0 (Immunoglobulin G)
RN  - EC 3.2.1.- (Hexosaminidases)
RN  - EC 3.2.1.- (chitotriosidase)
RN  - EC 3.2.1.45 (Glucosylceramidase)
RN  - EC 3.2.1.45 (Velaglucerase alfa, human)
RN  - Q6U6J48BWY (imiglucerase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Bone Density/drug effects
MH  - Chemokines, CC/blood
MH  - Child
MH  - Drug Administration Schedule
MH  - *Drug Substitution
MH  - *Enzyme Replacement Therapy
MH  - Female
MH  - Gaucher Disease/*drug therapy/enzymology/pathology
MH  - Glucosylceramidase/*therapeutic use
MH  - Hemoglobins/metabolism
MH  - Hexosaminidases/blood
MH  - Humans
MH  - Immunoglobulin G/blood
MH  - Liver/drug effects/enzymology/pathology
MH  - Male
MH  - Middle Aged
MH  - Organ Size/drug effects
MH  - Platelet Count
MH  - Prospective Studies
MH  - Spleen/drug effects/enzymology/pathology
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2015/03/18 06:00
MHDA- 2015/09/02 06:00
CRDT- 2015/03/18 06:00
PHST- 2014/11/21 00:00 [received]
PHST- 2015/02/20 00:00 [revised]
PHST- 2015/03/10 00:00 [accepted]
PHST- 2015/03/18 06:00 [entrez]
PHST- 2015/03/18 06:00 [pubmed]
PHST- 2015/09/02 06:00 [medline]
AID - 10.1002/ajh.24007 [doi]
PST - ppublish
SO  - Am J Hematol. 2015 Jul;90(7):592-7. doi: 10.1002/ajh.24007.