{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:04:52Z","timestamp":1792159492512,"version":"4.4.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T00:00:00Z","timestamp":1611187200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T00:00:00Z","timestamp":1611187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008484","name":"BioMarin Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008484","id-type":"DOI","asserted-by":"publisher"}]}],"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>We present baseline characteristics and follow-up data of a Managed Access Agreement (MAA), including patients with mucopolysaccharidosis IVA (MPS IVA) receiving elosulfase alfa enzyme replacement therapy (ERT) in England on a conditional basis. Patients enrolled in the MAA programme are reviewed on an annual basis. Therapy can be continued if patients are compliant, able to tolerate infusions, and meet four out of five pre-defined clinical and patient-reported outcomes (PRO) criteria. Baseline and follow-up clinical and PRO data are presented for all participants who completed\u2009\u2265\u20091\u00a0year of assessments in the MAA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The analysis included data from 55 patients, including 26 patients previously enrolled in clinical trials and 29 who started ERT after enrolling in the MAA. In patients with both baseline and follow-up data, mean 6-min walk test distance increased from 217\u00a0m at baseline to 244\u00a0m after a mean follow-up of 4.9\u00a0years. Improvement or stabilisation was seen regardless of age at treatment initiation or duration of treatment. Mean forced vital capacity and forced expiratory volume in 1\u00a0s were 0.87\u00a0L and 0.78\u00a0L, respectively at baseline and 1.05\u00a0L and 0.88\u00a0L after a mean follow-up of 5.5\u00a0years. PRO data showed overall improvements over time in Mobility, Self-care, and Caregiver assistance scores of the MPS-Health Assessment Questionnaire, relatively stable quality of life, and some improvements in pain scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The MAA data confirm the effects of elosulfase alfa on clinical and PRO results observed in the clinical trials and provide real-world evidence for long-term stabilisation in these measures, suggesting a positive impact on the natural history of MPS IVA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-021-01675-x","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T02:02:57Z","timestamp":1611194577000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Impact of long-term elosulfase alfa treatment on clinical and patient-reported outcomes in patients with mucopolysaccharidosis type IVA: results from a Managed Access Agreement in England"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1282-6315","authenticated-orcid":false,"given":"Maureen","family":"Cleary","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Davison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Gould","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarekegn","family":"Geberhiwot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derralynn","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Mercer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Morrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saikat","family":"Santra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Jarrett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina M.","family":"Stepien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,21]]},"reference":[{"key":"1675_CR1","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.ymgme.2013.04.002","volume":"110","author":"CJ Hendriksz","year":"2013","unstructured":"Hendriksz CJ, Harmatz P, Beck M, Jones S, Wood T, Lachman R, Gravance CG, Orii T, Tomatsu S. 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Institutional review board\/ethics committee oversight was not applicable; patients receiving elosulfase alfa under the managed access agreement received care from their treating physician in accordance with all local standards of care.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Maureen Cleary received personal fees from BioMarin for attending an advisory board related to this study, and personal fees for advisory boards and a travel grant to attend a metabolic meeting from BioMarin not related to his work. James Davison received an honorarium from BioMarin for attending an advisory board related to this study and personal fees for travel, accommodation and conference registration costs to attend a conference not related to the submitted work. Rachel Gould has received a non-restricted travel grant and participated in BioMarin advisory boards. Tarekegn Geberhiwot received personal fees from BioMarin for consultancy not related to this study. Derralynn Hughes received personal fees for advisory boards from BioMarin related to this study. Jean Mercer has nothing to disclose. Alexandra Morrison declares that MPS Commercial is a Private Limited Company trading as Rare Disease Research Partners and is a wholly owned, not-for-profit subsidiary of the Society for Mucopolysaccharide Diseases, UK. Rare Disease Research Partners provides professional PRO data collection services for the elosulfase alfa MAA under contract to BioMarin. Elaine Murphy has worked as a clinical trial investigator for BioMarin, related to this work. Saikat Santra has received non-restricted travel and educational grants, participated as an investigator in clinical research studies, and served on advisory boards for BioMarin. James Jarrett is an employee and stockholder of BioMarin. Swati Mukherjee is an employee and stockholder of BioMarin. Karolina Stepien has received speaker fees and a non-restricted travel and educational grant and participated in BioMarin advisory boards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"38"}}