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Orphanet J Rare Dis. 2017 Oct 3;12(1):161. doi: 10.1186/s13023-017-0712-3.

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

Author information

1
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. muenzer@med.unc.edu.
2
Medical Genetics Service/HCPA, Department of Genetics/UFRGS and INAGEMP, Porto Alegre, Brazil.
3
Rare Disease Centre, Helios Dr. Horst Schmidt Clinic, Wiesbaden, Germany.
4
Department of Women's and Children's Health, University of Padova, Padova, Italy.
5
Department of Pediatric Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.
6
Cytel, Inc., Geneva, Switzerland.
7
Department of Pediatrics, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.

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.

KEYWORDS:

Disease registry; Efficacy; Hunter syndrome; Idursulfase; Lysosomal storage disease

PMID:
28974237
PMCID:
PMC5627440
DOI:
10.1186/s13023-017-0712-3
[Indexed for MEDLINE]
Free PMC Article

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