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  • 标题:Evaluation of impact of anti-idursulfase antibodies during long-term idursulfase enzyme replacement therapy in mucopolysaccharidosis II patients
  • 本地全文:下载
  • 作者:R. Giugliani ; P. Harmatz ; S.A. Jones
  • 期刊名称:Molecular Genetics and Metabolism Reports
  • 印刷版ISSN:2214-4269
  • 出版年度:2017
  • 卷号:12
  • 页码:2-7
  • DOI:10.1016/j.ymgmr.2017.01.014
  • 出版社:Elsevier B.V.
  • 摘要:

    Objectives

    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.

  • 关键词:Neutralizing antibodies; Idursulfase; Hunter syndrome; Enzyme replacement therapy; Cognitive impairment; Immunogenicity; Glycosaminoglycans
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