Published in:
Open Access 01-12-2017 | Research
Clinical outcomes in idursulfase-treated patients with mucopolysaccharidosis type II: 3-year data from the hunter outcome survey (HOS)
Published in: Orphanet Journal of Rare Diseases | Issue 1/2017
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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.