title: Evaluation of impact of anti-idursulfase antibodies during long-term idursulfase enzyme replacement therapy in mucopolysaccharidosis II patients.
abstract: OBJECTIVE
  This 109-week, nonrandomized, observational study of mucopolysaccharidosis II (MPS II) patients already enrolled in the Hunter Outcome Survey (HOS) (NCT00882921), assessed the long-term immunogenicity of idursulfase, and examined the effect of idursulfase-specific antibody generation on treatment safety (via infusion-related adverse events [IRAEs]) and pharmacodynamics (via urinary glycosaminoglycans [uGAGs]).
  
  
  METHODS
  Male patients ≥ 5 years, enrolled in HOS regardless of idursulfase treatment status were eligible. Blood/urine samples for anti-idursulfase antibody testing and uGAG measurement were collected every 12 weeks.
  
  
  RESULTS
  Due to difficulties in enrolling treatment-naïve patients, data collection was limited to 26 enrolled patients of 100 planned patients (aged 5.1-35.5 years) all of whom were non-naïve to treatment. Fifteen (58%) patients completed the study. There were 11/26 (42%) seropositive patients at baseline (Ab +), and 2/26 (8%) others developed intermittent seropositivity by Week 13. A total of 9/26 patients (35%) had ≥ 1 sample positive for neutralizing antibodies. Baseline uGAG levels were low due to prior idursulfase treatment and did not change appreciably thereafter. Ab + patients had persistently higher uGAG levels at entry and throughout the study than Ab - patients. Nine of 26 (34%) patients reported IRAEs. Ab + patients appeared to have a higher risk of developing IRAEs than Ab - patients. However, the relative risk was not statistically significant and decreased after adjustment for age.
  
  
  CONCLUSIONS
  50% of study patients developed idursulfase antibodies. Notably Ab + patients had persistently higher average uGAG levels. A clear association between IRAEs and antibodies was not established.
authors.affiliation: Department of Genetics/UFRGS, Medical Genetics Service/HCPA, INAGEMP, Porto Alegre, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Giugliani
authors.affiliation: UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Harmatz
authors.affiliation: Manchester Centre for Genomic Medicine, St Mary's Hospital, MAHSC, Manchester, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Jones
authors.affiliation: Genomic Medicine Program, Children's Hospitals and Clinics of Minnesota, and Division of Medical Genetics, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Mendelsohn
authors.affiliation: Metabolic Medicine Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Vellodi
authors.affiliation: Shire, Lexington, MA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Paediatrics and Child Health, University of Pretoria, Steve Biko Academic Unit, Pretoria, South Africa.
authors.forename: C J
authors.initials: CJ
authors.lastname: Hendriksz
authors.affiliation: Department of Clinical Inherited Metabolic Disorders, Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK.
authors.forename: S
authors.initials: S
authors.lastname: Vijayaraghavan
authors.affiliation: Shire, Lexington, MA, USA.
authors.forename: D A H
authors.initials: DA
authors.lastname: Whiteman
authors.affiliation: Shire, Lexington, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Pano
keywords: Cognitive impairment; Enzyme replacement therapy; Glycosaminoglycans; Hunter syndrome; Idursulfase; Immunogenicity; Neutralizing antibodies