Clinical outcomes in idursulfase-treated patients with mucopolysaccharidosis type II: 3-year data from the hunter outcome survey (HOS) Public Deposited

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  • Beck, Michael
    • Other Affiliation: Department of Pediatrics, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany
  • Tylki-Szymańska, Anna
    • Other Affiliation: Department of Pediatric Nutrition and Metabolic Diseases, The Children’s Memorial Health Institute, Warsaw, Poland
  • Giugliani, Roberto
    • Other Affiliation: Medical Genetics Service/HCPA, Department of Genetics/UFRGS and INAGEMP, Porto Alegre, Brazil
  • Jego, Virginie
    • Other Affiliation: Cytel, Inc., Geneva, Switzerland
  • Scarpa, Maurizio
    • Other Affiliation: Rare Disease Centre, Helios Dr. Horst Schmidt Clinic, Wiesbaden, Germany; Department of Women’s and Children’s Health, University of Padova, Padova, Italy
  • Muenzer, Joseph
    • Affiliation: School of Medicine, Department of Pediatrics
Abstract
  • Abstract Background Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare, X-linked disorder caused by deficient activity of the enzyme iduronate-2-sulfatase (I2S). Treatment is available in the form of enzyme replacement therapy (ERT) with recombinant I2S. Clinical outcomes following ≥3 years of ERT with idursulfase were investigated in a broad population of patients with MPS II enrolled in the Hunter Outcome Survey (HOS). Methods As of January 2016, 639 patients (excluding female patients, individuals who had received a bone marrow transplant and those enrolled in the phase 1/2 [TKT018] or phase 2/3 [TKT024] clinical trial) followed prospectively in the registry had received idursulfase for ≥6 months. These individuals all had data available for ≥1 clinical parameter at baseline and ≥1 additional time point following treatment initiation. Changes in clinical parameters were assessed in the subcohorts of patients with a measurement at baseline and at year 1, 2 or 3 of treatment. Safety data from patients who started treatment at or after enrollment in HOS (n = 233) were also assessed. Results Median (10th, 90th percentiles) age at first treatment was 6.2 (2.1, 18.2) years and median treatment duration was 56.3 (18.2, 97.6) months. Urinary glycosaminoglycan (uGAG) levels decreased from baseline to year 3 in patients with data available at this time point (median change from baseline: −201.0 [−591.4, −21.9] μg/mg creatinine [n = 121]). Improvements in the following parameters were observed at year 3 in the subcohorts: 6-min walking test (6MWT) distance, 10.6 (−33.6, 50.8)% (n = 26); left ventricular mass index (LVMI), −9.3 (−31.5, 19.7)% (n = 52); absolute forced vital capacity (FVC), 29.7 (−13.4, 66.7)% (n = 23); absolute forced expiratory volume in 1 s (FEV1), 22.8 (−15.2, 62.1)% (n = 22); palpable liver size, −54.5 (−85.7, 50.0)% (n = 53); palpable spleen size, −33.3 (−80.0, 33.3)% (n = 17). No new or unexpected safety concerns were identified in this analysis. Conclusions These findings suggest that idursulfase has a positive effect on uGAG levels, 6MWT results, LVMI, FVC, FEV1 and hepatosplenomegaly after 1, 2 and 3 years treatment.
Date of publication
Identifier
  • doi:10.1186/s13023-017-0712-3
Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • The Author(s).
Language
  • English
Bibliographic citation
  • Orphanet Journal of Rare Diseases. 2017 Oct 03;12(1):161
Publisher
  • BioMed Central
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