Effectiveness of early initiation of idursulfase in infants and very young children with mucopolysaccharidosis II: a retrospective chart review in siblings

Introduction Enzyme replacement therapy (ERT) with intravenous idursulfase is the standard of care for patients with mucopolysaccharidosis II (MPS II; Hunter syndrome). Data are limited for children aged ≤12 months. This retrospective study evaluated outcomes with early ERT. Methods Male siblings with MPS II treated with idursulfase for >2 years were categorized into five cohorts by age at treatment initiation. The primary objective compared Cohort 1 (ERT initiation aged ≤12 months) with Cohort 2 (ERT initiation at an age ≥ 12 months older). Clinical outcomes were compared using Kaplan–Meier and Cox proportional models, and generalized linear mixed models (GLMMs) for variables with adequate data. Results Overall, 38 patients (19 sibling pairs) were included; the primary analysis included 15 per cohort. Median (10th–90th percentile) age at idursulfase initiation was 3.0 (1.0–11.0) and 44.0 (28.0–84.0) months and mean (standard deviation) follow-up was 69.7 (42.5) and 130.6 (46.8) months in Cohorts 1 and 2, respectively. First events from birth of abnormal liver size, joint stiffness, carpal tunnel syndrome, and enlarged tonsils and adenoids occurred less frequently in Cohort 1 than 2; first events of surgery or cardiac valve disease occurred more frequently in Cohort 1 than 2. GLMM analyses showed that, compared with their older siblings, patients who initiated ERT aged ≤12 months had better clinical outcomes for height-for-age Z -score, liver, cardiac, and musculoskeletal manifestations. Discussion Early ERT may improve clinical outcomes in MPS II, supporting the known efficacy of idursulfase and adding to the limited evidence for early ERT.