Clinical response to long term enzyme replacement treatment in children, adolescent and adult patients with Hunter syndrome

Serra, J. Dalmau; Vitoria, Isidro; Fernández, Rafael Calderón; Aznar, Ismael

doi:10.1016/j.medcli.2015.06.015

Cited by 12 publications

(7 citation statements)

References 29 publications

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“…Consistent with findings from the phase 1/2 study and other small-scale studies on the effectiveness of idursulfase [ 26 , 30 , 32 , 34 ], we observed improvements in LVMI compared with baseline with each year of treatment in our analysis. Although the patient numbers in our analysis were too small to mathematically evaluate any formal relationship between the development of hypertrophic cardiomyopathy and treatment with idursulfase, it is recognized that this condition is frequently reported in untreated patients with mucopolysaccharidoses, and in MPS II in particular [ 37 ].…”

Section: Discussionsupporting

confidence: 91%

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

Muenzer

Giugliani

Scarpa

et al. 2017

Orphanet J Rare Dis

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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.Electronic supplementary materialThe online version of this article (10.1186/s13023-017-0712-3) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 91%

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

Muenzer

Giugliani

Scarpa

et al. 2017

Orphanet J Rare Dis

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“…Overall, these results suggest that the benefits associated with IV idursulfase treatment observed in the initial clinical trials [ 10 , 12 ] and after 3 years of treatment in routine clinical practice [ 11 ] are maintained in the longer term. The results are also in line with observations in localized studies of smaller numbers of IV idursulfase-treated patients, including one with 10 years of follow-up [ 13 – 16 ], and provide valuable support for these findings in a larger and more diverse population of patients with MPS II.…”

Section: Discussionsupporting

confidence: 87%

“…However, many patients with MPS II have now been receiving treatment with IV idursulfase for over 5 years and there is a need to improve our understanding of the long-term outcomes for patients after extended periods of treatment. Although some studies have evaluated outcomes for longer periods, including 10 years of follow-up, these were generally small-scale with geographically limited populations (mostly single-center studies) and the clinical parameters studied varied [ 13 – 16 ]. It is also important to explore the influence of variables such as the age at treatment initiation on overall outcomes because data in this area remain limited.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the long-term treatment effects of intravenous idursulfase in patients with mucopolysaccharidosis II (MPS II) using statistical modeling: data from the Hunter Outcome Survey (HOS)

Muenzer

Botha

Harmatz

et al. 2021

Orphanet J Rare Dis

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Background Mucopolysaccharidosis II (MPS II; Hunter syndrome) is a rare, life-limiting lysosomal storage disease caused by deficient iduronate-2-sulfatase activity. Enzyme replacement therapy (ERT) with intravenous (IV) idursulfase can stabilize or improve many somatic manifestations, but there remains a need for further analysis of long-term treatment outcomes. Using data from patients with MPS II enrolled in the Hunter Outcome Survey (HOS), mixed modeling was performed to evaluate and predict the effects of IV idursulfase treatment on selected clinical parameters for up to 8 years following treatment start. The modeling population comprised male patients followed prospectively in HOS who had received IV idursulfase for at least 5 years and who had data available for two or more time points (at least one post-ERT). Age at ERT start and time since ERT start were included as covariates. Results In total, 481 patients were eligible for inclusion in at least one model. At 8 years post-ERT start, improvement from baseline was predicted for each age group (< 18 months, 18 months to < 5 years and ≥ 5 years at treatment start) in the following parameters: mean urinary glycosaminoglycan levels (percentage changes of > –75% in each group), mean left ventricular mass index (decreases of ~ 1 g/m2) and mean palpable liver size (decreases of > 2 cm). Improvements in mean 6-min walk test distance (increase of > 50 m) and stabilization in percent predicted forced vital capacity and forced expiratory volume in 1 s (decreases of ~ 4 and ~ 9 percentage points, respectively) at 8 years post-ERT start were predicted for patients aged ≥ 5 years at ERT start (these assessments are unsuitable for patients aged < 5 years). Predicted changes over time were similar across the three age groups; however, overall outcomes were most favorable in children aged < 18 months at ERT start. Conclusions These findings suggest that the previously reported positive effects of IV idursulfase on the somatic manifestations of MPS II are predicted to be maintained for at least 8 years following ERT initiation and highlight the value of statistical modeling to predict long-term treatment outcomes in patients with rare diseases.

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“…Ancak, yaşamın erken dönemlerinde (ilk birkaç ay içinde) ERT başlanmasının kapak tutulumunu önlediği bildirilmiştir. Bu nedenle hastalığın erken tanısı ve ERT'nin erken dönemde başlanması oldukça önemlidir [58].…”

Section: Tedavi Ve Izlemunclassified

Pediatrik metabolik hastalıklarda kardiyovasküler bulgular

Elkiran

2019

Pamukkale Medical Journal

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Özet Kardiyak bulgular pediatrik metabolik hastalıkların birçoğuna eşlik eden önemli bir klinik sorundur. Hatta bazı metabolik hastalıklarda hastalığın ilk klinik bulgusu kardiyak bulgular olabilir. Kardiyak bulgular hastalığın seyrinde morbidite ve mortalitede önemli artışa neden olmaktadır. Kardiyomiyopati metabolik hastalıklarda en sık görülen kardiyak problemdir. Bununla birlikte, mitokondriyal bozukluklar ve organik asidemilerde aritmiler, depo hastalıklarında ise kapak tutulumu daha belirgin bulgudur. Bu hastalıkların erken tanı ve tedavisi ile kardiyovasküler sorunlar da önemli bir oranda azalacaktır. Bu nedenle, metabolik hastalıklı çocukların takiplerinde kardiyak tutulum açısından mutlaka sistematik tarama yapılmalıdır.

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Clinical response to long term enzyme replacement treatment in children, adolescent and adult patients with Hunter syndrome

Cited by 12 publications

References 29 publications

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

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

Evaluation of the long-term treatment effects of intravenous idursulfase in patients with mucopolysaccharidosis II (MPS II) using statistical modeling: data from the Hunter Outcome Survey (HOS)

Pediatrik metabolik hastalıklarda kardiyovasküler bulgular

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