Clinical outcomes in idursulfase-treated patients with mucopolysaccharidosis type II: 3-year data from the hunter outcome survey (HOS)
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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2017-10-01
|
| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13023-017-0712-3 |
| _version_ | 1818925914181861376 |
|---|---|
| author | Joseph Muenzer Roberto Giugliani Maurizio Scarpa Anna Tylki-Szymańska Virginie Jego Michael Beck |
| author_facet | Joseph Muenzer Roberto Giugliani Maurizio Scarpa Anna Tylki-Szymańska Virginie Jego Michael Beck |
| author_sort | Joseph Muenzer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T02:48:47Z |
| format | Article |
| id | doaj.art-ae8b3e09268942928ca9f56510a11dfb |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-20T02:48:47Z |
| publishDate | 2017-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-ae8b3e09268942928ca9f56510a11dfb2022-12-21T19:56:06ZengBMCOrphanet Journal of Rare Diseases1750-11722017-10-0112111110.1186/s13023-017-0712-3Clinical outcomes in idursulfase-treated patients with mucopolysaccharidosis type II: 3-year data from the hunter outcome survey (HOS)Joseph Muenzer0Roberto Giugliani1Maurizio Scarpa2Anna Tylki-Szymańska3Virginie Jego4Michael Beck5Department of Pediatrics, University of North Carolina at Chapel HillMedical Genetics Service/HCPA, Department of Genetics/UFRGS and INAGEMPRare Disease Centre, Helios Dr. Horst Schmidt ClinicDepartment of Pediatric Nutrition and Metabolic Diseases, The Children’s Memorial Health InstituteCytel, Inc.Department of Pediatrics, University Medical Center, Johannes Gutenberg University MainzAbstract 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.http://link.springer.com/article/10.1186/s13023-017-0712-3Hunter syndromeLysosomal storage diseaseIdursulfaseEfficacyDisease registry |
| spellingShingle | Joseph Muenzer Roberto Giugliani Maurizio Scarpa Anna Tylki-Szymańska Virginie Jego Michael Beck Clinical outcomes in idursulfase-treated patients with mucopolysaccharidosis type II: 3-year data from the hunter outcome survey (HOS) Orphanet Journal of Rare Diseases Hunter syndrome Lysosomal storage disease Idursulfase Efficacy Disease registry |
| title | Clinical outcomes in idursulfase-treated patients with mucopolysaccharidosis type II: 3-year data from the hunter outcome survey (HOS) |
| title_full | Clinical outcomes in idursulfase-treated patients with mucopolysaccharidosis type II: 3-year data from the hunter outcome survey (HOS) |
| title_fullStr | Clinical outcomes in idursulfase-treated patients with mucopolysaccharidosis type II: 3-year data from the hunter outcome survey (HOS) |
| title_full_unstemmed | Clinical outcomes in idursulfase-treated patients with mucopolysaccharidosis type II: 3-year data from the hunter outcome survey (HOS) |
| title_short | Clinical outcomes in idursulfase-treated patients with mucopolysaccharidosis type II: 3-year data from the hunter outcome survey (HOS) |
| title_sort | clinical outcomes in idursulfase treated patients with mucopolysaccharidosis type ii 3 year data from the hunter outcome survey hos |
| topic | Hunter syndrome Lysosomal storage disease Idursulfase Efficacy Disease registry |
| url | http://link.springer.com/article/10.1186/s13023-017-0712-3 |
| work_keys_str_mv | AT josephmuenzer clinicaloutcomesinidursulfasetreatedpatientswithmucopolysaccharidosistypeii3yeardatafromthehunteroutcomesurveyhos AT robertogiugliani clinicaloutcomesinidursulfasetreatedpatientswithmucopolysaccharidosistypeii3yeardatafromthehunteroutcomesurveyhos AT maurizioscarpa clinicaloutcomesinidursulfasetreatedpatientswithmucopolysaccharidosistypeii3yeardatafromthehunteroutcomesurveyhos AT annatylkiszymanska clinicaloutcomesinidursulfasetreatedpatientswithmucopolysaccharidosistypeii3yeardatafromthehunteroutcomesurveyhos AT virginiejego clinicaloutcomesinidursulfasetreatedpatientswithmucopolysaccharidosistypeii3yeardatafromthehunteroutcomesurveyhos AT michaelbeck clinicaloutcomesinidursulfasetreatedpatientswithmucopolysaccharidosistypeii3yeardatafromthehunteroutcomesurveyhos |