Giugliani, R.Harmatz, P.Jones, S.A.Mendelsohn, N.J.Vellodi, A.Qiu, Y.Hendriksz, Christian J.Vijayaraghavan, S.Whiteman, D.A.H.PAno, A.2017-03-142017-03-142017-09Giugliani, R, Harmatz, P, Jones, SA, Mendelsohn, NJ, Vellodi, A, Qiu, Y, Hendriksz, CJ, Vijayaraghavan, S,, Whiteman, DAH & Pano, A 2017, 'Evaluation of impact of anti-idursulfase antibodies during long-term idursulfase enzyme replacement therapy in mucopolysaccharidosis II patients', Molecular Genetics and Metabolism Reports, vol. 12, pp. 2-7.2214-426910.1016/j.ymgmr.2017.01.014http://hdl.handle.net/2263/59422OBJECTIVES : 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.en© 2017 Published by Elsevier Inc. This is an open access article under te CC BY-NC-ND license ( http:// creativecommons.org/li censes/by-nc-nd/4.0/ ).Neutralizing antibodiesIdursulfaseHunter syndromeEnzyme replacement therapyCognitive impairmentImmunogenicityGlycosaminoglycansInfusion-related adverse event (IRAE)Mucopolysaccharidosis II (MPS II)Urinary glycosaminoglycan (uGAG)Hunter outcome survey (HOS)Article