title: A multicenter, open-label study evaluating safety and clinical outcomes in children (1.4-7.5 years) with Hunter syndrome receiving idursulfase enzyme replacement therapy.
abstract: OBJECTIVE
  The primary objective of this study was to determine the safety of idursulfase in Hunter syndrome patients aged 5 years or younger.
  
  
  METHODS
  Idursulfase (0.5 mg/kg) was administered intravenously on a weekly basis (52 infusions per patient) in an open-label study. Safety monitoring included adverse events, anti-idursulfase antibodies, vital signs, physical examination, 12-lead electrocardiogram, concomitant medications or procedures, and laboratory testing (clinical chemistry, hematology, and urinalysis). The following exploratory efficacy outcomes were assessed at baseline and at weeks 18 or 36 or 53: urinary glycosaminoglycan levels, liver or spleen size, developmental milestones, and growth indices. Pharmacokinetic parameters were assessed at week 27.
  
  
  RESULTS
  Twenty-eight boys aged 1.4-7.5 years were enrolled (one discontinued for noncompliance) in the study. All the patients reported adverse events (16 patients (57%) reported possibly or probably treatment-related adverse events). The only severe adverse event was sleep apnea (two patients); others were mild or moderate. Sixteen patients had infusion-related adverse events, a similar proportion as previously reported. Thirteen patients (46%) experienced at least one serious adverse event: pyrexia and bronchopneumonia were the most common (three patients each). No clinically important drug-related changes in laboratory parameters or vital signs or electrocardiograms were reported. Nineteen patients (68%) developed anti-idursulfase immunoglobulin G antibodies. Growth rates remained within normal age-related ranges. Developmental quotients were lower than normal but remained stable. By week 18, organ size and urinary glycosaminoglycan levels decreased as compared with baseline and remained stable throughout the study.
  
  
  CONCLUSIONS
  Idursulfase safety, tolerability, and efficacy were similar to that previously reported in males ≥5 years.
authors.affiliation: 1] Department of Genetics, Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil [2] National Institute of Medical Genetics Population (INAGEMP), Porto Alegre, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.affiliation: Department of Pediatrics and Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Wuh-Liang
authors.initials: WL
authors.lastname: Hwu
authors.affiliation: Department of Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Tylki-Szymanska
authors.affiliation: Shire, Lexington, Massachusetts, USA.
authors.forename: David A H
authors.initials: DA
authors.lastname: Whiteman
authors.affiliation: Shire, Lexington, Massachusetts, USA.
authors.forename: Arian
authors.initials: A
authors.lastname: Pano
mesh_terms: D000888:Antibodies, Anti-Idiotypic; D002648:Child; D002675:Child, Preschool; D056947:Enzyme Replacement Therapy; D005500:Follow-Up Studies; D006025:Glycosaminoglycans / Q000652:urine; D006801:Humans; D007066:Iduronate Sulfatase / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D007223:Infant; D008099:Liver / Q000187:drug effects; D008297:Male; D016532:Mucopolysaccharidosis II / Q000188:drug therapy*; D013154:Spleen / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000888:Antibodies, Anti-Idiotypic; D006025:Glycosaminoglycans; C048844:anti-IgG; D007066:Iduronate Sulfatase; C517982:idursulfase