Abstract
BackgroundMucopolysaccharidosis 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).MethodsAs 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.ResultsMedian (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.ConclusionsThese 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.
Highlights
Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare, X-linked disorder caused by deficient activity of the enzyme iduronate-2-sulfatase (I2S)
Our results show improvements in Urinary glycosaminoglycan (uGAG) levels, 6-min walking test (6MWT) distance, left ventricular mass index (LVMI), absolute forced vital capacity (FVC), absolute forced expiratory volume in 1 s (FEV1) and palpable liver and spleen size compared with baseline after 1, 2 and 3 years of treatment
The clinical parameters analysed were selected to match the endpoints studied in the phase 2/3 clinical trial of intravenous idursulfase in patients with MPS II, the 2-year open-label extension period, as well as a phase 4 open-label single-arm study of idursulfase treatment in boys with MPS II who were less than 5 years of age [7,8,9]
Summary
Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare, X-linked disorder caused by deficient activity of the enzyme iduronate-2-sulfatase (I2S). Mucopolysaccharidosis type II (MPS II; Hunter syndrome; OMIM 309900) is a rare, X-linked recessive, life-limiting metabolic disease [1], with an estimated incidence of 0.6– 1.3 in 100,000 live male births [2, 3]. It is caused by deficient activity of iduronate-2-sulfatase (I2S), a lysosomal enzyme that catalyses a step in the catabolism of glycosaminoglycan (GAG). Disease progression is often slower in individuals without cognitive impairment, with patients with normal cognitive function typically surviving into adulthood [1, 5]
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