title: Long-term follow-up of endurance and safety outcomes during enzyme replacement therapy for mucopolysaccharidosis VI: Final results of three clinical studies of recombinant human N-acetylgalactosamine 4-sulfatase.
abstract: The objective of this study was to evaluate the long-term clinical benefits and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome), a lysosomal storage disease. Fifty-six patients derived from 3 clinical studies were followed in open-label extension studies for a total period of 97-260 Weeks. All patients received weekly infusions of rhASB at 1 mg/kg. Efficacy was evaluated by (1) distance walked in a 12-minute walk test (12MWT) or 6-minute walk test (6MWT), (2) stairs climbed in the 3-minute stair climb (3MSC), and (3) reduction in urinary glycosaminoglycans (GAG). Safety was evaluated by compliance, adverse event (AE) reporting and adherence to treatment.
  
  
  RESULTS
  A significant reduction in urinary GAG (71-79%) was sustained. For the 12MWT, subjects in Phase 2 showed improvement of 255+/-191 m (mean+/-SD) at Week 144; those in Phase 3 Extension demonstrated improvement from study baseline of 183+/-26 m (mean+/- SE) in the rhASB/rhASB group at Week 96 and from treatment baseline (Week 24) of 117+/-25 m in the placebo/rhASB group. The Phase 1/2 6MWT and the 3MSC from Phase 2 and 3 also showed sustained improvements through the final study measurements. Compliance was 98% overall. Only 560 of 4121 reported AEs (14%) were related to treatment with only 10 of 560 (2%) described as severe.
  
  
  CONCLUSIONS
  rhASB treatment up to 5 years results in sustained improvements in endurance and has an acceptable safety profile.
authors.affiliation: Children's Hospital & Research Center Oakland, 747 52nd Street, Oakland, CA 94609, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.affiliation: Serviço de Genética Médica/HCPA and Department of Genetics/UFRGS, Porto Alegre, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.affiliation: Serviço de Genética Médica/HCPA and Department of Genetics/UFRGS, Porto Alegre, Brazil.
authors.forename: Ida Vanessa
authors.initials: IV
authors.lastname: D Schwartz
authors.affiliation: Hôpital Edouard Herriot Pavillon S, Maladies Metaboliques, Lyon, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Guffon
authors.affiliation: Unidade de Doenças Metabólicas, Departamento Pediatria, Hospital de Sao João, Porto, Portugal.
authors.forename: Elisa Leão
authors.initials: EL
authors.lastname: Teles
authors.affiliation: Unidade de Biologia do Lisossoma e Peroxisoma, Instituto de Biologia Molecular e Celular, Porto, Portugal.
authors.forename: M Clara Sá
authors.initials: MCS
authors.lastname: Miranda
authors.affiliation: Royal Manchester Children's Hospital, Manchester, UK.
authors.forename: J Edmond
authors.initials: JE
authors.lastname: Wraith
authors.affiliation: Children's Hospital, University of Mainz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Beck
authors.affiliation: Children's Hospital, University of Mainz, Germany.
authors.forename: Laila
authors.initials: L
authors.lastname: Arash
authors.affiliation: Department of Pediatrics, University of Padova, Padova, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Scarpa
authors.affiliation: Department of Genetic Medicine, Women's and Children's Hospital Adelaide, North Adelaide, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ketteridge
authors.affiliation: Department of Genetic Medicine, Women's and Children's Hospital Adelaide, North Adelaide, Australia.
authors.forename: John J
authors.initials: JJ
authors.lastname: Hopwood
authors.affiliation: Univ. Klinik fur Kinder und Jugendheilkunde, Graz, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Plecko
authors.affiliation: Departments of Pediatrics and Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Steiner
authors.affiliation: University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Chester B
authors.initials: CB
authors.lastname: Whitley
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Paige
authors.initials: P
authors.lastname: Kaplan
authors.affiliation: Statistics Collaborative, Inc., Washington, DC, USA.
authors.forename: Zi-Fan
authors.initials: ZF
authors.lastname: Yu
authors.affiliation: BioMarin Pharmaceutical Inc, Novato, CA, USA.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Swiedler
authors.affiliation: BioMarin Pharmaceutical Inc, Novato, CA, USA.
authors.forename: Celeste
authors.initials: C
authors.lastname: Decker
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006025:Glycosaminoglycans / Q000652:urine; D006801:Humans; D008297:Male; D009043:Motor Activity; D009087:Mucopolysaccharidosis VI / Q000503:physiopathology / Q000628:therapy*; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D016138:Walking
chemical_list: D006025:Glycosaminoglycans; D011994:Recombinant Proteins; D020051:N-Acetylgalactosamine-4-Sulfatase