{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:16:40Z","timestamp":1792030600604,"version":"4.4.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T00:00:00Z","timestamp":1635552000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T00:00:00Z","timestamp":1635552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Shire"},{"name":"Takeda Development Center Americas, Inc."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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\u00a0years following treatment start. The modeling population comprised male patients followed prospectively in HOS who had received IV idursulfase for at least 5\u00a0years 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, 481 patients were eligible for inclusion in at least one model. At 8\u00a0years post-ERT start, improvement from baseline was predicted for each age group (&lt;\u200918\u00a0months, 18\u00a0months to\u2009&lt;\u20095\u00a0years and\u2009\u2265\u20095\u00a0years at treatment start) in the following parameters: mean urinary glycosaminoglycan levels (percentage changes of\u2009&gt;\u2009\u201375% in each group), mean left ventricular mass index (decreases of\u2009~\u20091\u00a0g\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) and mean palpable liver size (decreases of\u2009&gt;\u20092\u00a0cm). Improvements in mean 6-min walk test distance (increase of\u2009&gt;\u200950\u00a0m) and stabilization in percent predicted forced vital capacity and forced expiratory volume in 1\u00a0s (decreases of\u2009~\u20094 and\u2009~\u20099 percentage points, respectively) at 8\u00a0years post-ERT start were predicted for patients aged\u2009\u2265\u20095\u00a0years at ERT start (these assessments are unsuitable for patients aged\u2009&lt;\u20095\u00a0years). Predicted changes over time were similar across the three age groups; however, overall outcomes were most favorable in children aged\u2009&lt;\u200918\u00a0months at ERT start.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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\u00a0years following ERT initiation and highlight the value of statistical modeling to predict long-term treatment outcomes in patients with rare diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-021-02052-4","type":"journal-article","created":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T06:02:39Z","timestamp":1635573759000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["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)"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4035-6592","authenticated-orcid":false,"given":"Joseph","family":"Muenzer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaco","family":"Botha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Harmatz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Giugliani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Kampmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara K.","family":"Burton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,30]]},"reference":[{"key":"2052_CR1","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.ymgme.2017.05.016","volume":"121","author":"SA Khan","year":"2017","unstructured":"Khan SA, Peracha H, Ballhausen D, Wiesbauer A, Rohrbach M, Gautschi M, et al. 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Acta Paediatr. 2012;101:e42\u20137.","journal-title":"Acta Paediatr"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-021-02052-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-021-02052-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-021-02052-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T06:07:50Z","timestamp":1635574070000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-021-02052-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,30]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2052"],"URL":"https:\/\/doi.org\/10.1186\/s13023-021-02052-4","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,30]]},"assertion":[{"value":"24 February 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Independent Review Board\/Ethics Committee approval was obtained for all participating centers. HOS is conducted in accordance with Good Pharmacoepidemiological Practices (GPP), Good Research for Comparative Effectiveness principles and the relevant principles of the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines (ICH E6). Each patient, their parents or a legal representative provided signed and dated written informed consent for participation in HOS. All patient information is managed in accordance with national data protection standards.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Each patient, their parents or a legal representative provided informed consent for publication of data.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"JM has received consulting fees from and\/or participated in advisory boards for Bluebird Bio, Denali Therapeutics, Homology Medicines, JCR Pharmaceuticals, REGENXBIO, Sanofi Genzyme and Shire (a Takeda company). He is a Principal Investigator for phase 1\/2 and phase 2\/3 intrathecal enzyme replacement trials for the neuronopathic form of MPS II (sponsored by Shire, a Takeda company), a phase 1\/2 gene editing trial for adults with MPS II (sponsored by Sangamo Therapeutics) and a phase 1\/2 intravenous enzyme replacement therapy trial for MPS IIIA (sponsored by Swedish Orphan Biovitrum). JB is a full-time employee of Takeda and stockholder of Takeda Pharmaceuticals Company Limited. PH has received consulting fees and\/or fees for service from Aeglea BioTherapeutics, Alexion Pharmaceuticals, ArmaGen, Audentes Therapeutics, BioMarin Pharmaceutical, Chiesi Farmaceutici, Denali Therapeutics, Enzyvant, Homology Medicines, Inventiva Pharma, JCR Pharmaceuticals, Orphazyme, Paradigm Biopharma, Pfizer, PTC Therapeutics, REGENXBIO, Sangamo Therapeutics, Sanofi Genzyme, Shire (a Takeda company), Swedish Orphan Biovitrum and Ultragenyx Pharmaceutical. RG has received consulting fees, fees for service, speaker fees and\/or travel expenses from and\/or participated in advisory boards for Abeona Therapeutics, Alnylam Pharmaceuticals, Amicus Therapeutics, BioMarin Pharmaceutical, Chiesi Farmaceutici, Denali Therapeutics, Inventiva Pharma, Janssen Pharmaceuticals, JCR Pharmaceuticals, Novartis, Orphan Disease Center, REGENXBIO, Sanofi Genzyme, Shire (a Takeda company), Sigilon Therapeutics, Swedish Orphan Biovitrum and Ultragenyx Pharmaceutical. He has performed contracted research for Allievex, Amicus Therapeutics, Idorsia Pharmaceuticals, JCR Pharmaceuticals, Lysogene, Sanofi Genzyme, Shire (a Takeda company) and Ultragenyx Pharmaceutical. CK has no competing interests to declare. BKB has received consulting and\/or speaker fees from and\/or participated in advisory boards for Aeglea, Agios, Alexion Pharmaceuticals, BioMarin Pharmaceutical, Chiesi Farmaceutici, Denali Therapeutics, Horizon Therapeutics, Inventiva Pharma, JCR Pharmaceuticals, Moderna, Pfizer, REGENXBIO, Reneo Pharmaceuticals, Sanofi Genzyme and Shire (a Takeda company). She has performed contracted research for Shire (a Takeda company) and has been involved in company-sponsored clinical trials with BioMarin Pharmaceutical, Homology Medicines, Sangamo Therapeutics, Shire (a Takeda company) and Ultragenyx Pharmaceutical.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"456"}}