Enzyme replacement therapy for mucopolysaccharidosis VI: evaluation of long-term pulmonary function in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase.
Pulmonary function is impaired in untreated mucopolysaccharidosis type VI (MPS VI). Pulmonary function was studied in patients during long-term enzyme replacement therapy (ERT) with recombinant human arylsulfatase B (rhASB; rhN-acetylgalactosamine 4-sulfatase). Pulmonary function tests prior to and for up to 240 weeks of weekly infusions of rhASB at 1 mg/kg were completed in 56 patients during Phase 1/2, Phase 2, Phase 3 and Phase 3 Extension trials of rhASB and the Survey Study. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and, in a subset of patients, maximum voluntary ventilation (MVV), were analyzed as absolute volume in liters. FEV1 and FVC showed little change from baseline during the first 24 weeks of ERT, but after 96 weeks, these parameters increased over baseline by 11% and 17%, respectively. This positive trend compared with baseline continued beyond 96 weeks of treatment. Improvements from baseline in pulmonary function occurred along with gains in height in the younger group (5.5% change) and in the older patient group (2.4% change) at 96 weeks. Changes in MVV occurred earlier within 24 weeks of treatment to approximately 15% over baseline. Model results based on data from all trials showed significant improvements in the rate of change in pulmonary function during 96 weeks on ERT, whereas little or no improvement was observed for the same time period prior to ERT. Thus, analysis of mean percent change data and longitudinal modeling both indicate that long-term ERT resulted in improvement in pulmonary function in MPS VI patients.
Harmatz
Paul
P
Children's Hospital & Research Center Oakland, CA 94609, USA. Pharmatz@mail.cho.org
Yu
Zi-Fan
ZF
Giugliani
Roberto
R
Schwartz
Ida Vanessa D
IV
Guffon
Nathalie
N
Teles
Elisa Leão
EL
Miranda
M Clara Sá
MC
Wraith
J Edmond
JE
Beck
Michael
M
Arash
Laila
L
Scarpa
Maurizio
M
Ketteridge
David
D
Hopwood
John J
JJ
Plecko
Barbara
B
Steiner
Robert
R
Whitley
Chester B
CB
Kaplan
Paige
P
Swiedler
Stuart J
SJ
Hardy
Karen
K
Berger
Kenneth I
KI
Decker
Celeste
C
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D006801:Humans; D008137:Longitudinal Studies; D008168:Lung / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D009087:Mucopolysaccharidosis VI / Q000097:blood* / Q000503:physiopathology* / Q000628:therapy; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000627:therapeutic use*; D010919:Placebos; D011994:Recombinant Proteins / Q000378:metabolism; D012107:Research Design; D012129:Respiratory Function Tests
D010919:Placebos; D011994:Recombinant Proteins; D020051:N-Acetylgalactosamine-4-Sulfatase