Evaluation of impact of anti-idursulfase antibodies during long-term idursulfase enzyme replacement therapy in mucopolysaccharidosis II patients

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.