{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:16:17Z","timestamp":1790806577705,"version":"4.1.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T00:00:00Z","timestamp":1712880000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T00:00:00Z","timestamp":1712880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Shire, a Takeda company"},{"DOI":"10.13039\/100008373","name":"Takeda Pharmaceutical Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008373","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Takeda Development Center Americas, Inc"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mucopolysaccharidosis II (MPS II) is a rare lysosomal storage disease characterized by iduronate-2-sulfatase\u00a0gene (<jats:italic>IDS<\/jats:italic>) deficiency and downstream glycosaminoglycan accumulation. Two-thirds of patients present with neuronopathic disease and evaluating cognitive function in these patients is challenging owing to limitations of currently available tests. During the clinical development of intrathecal idursulfase (idursulfase-IT), regulatory authorities requested qualitative data to further understand the neurocognitive changes observed by the investigators through the clinical trials.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This qualitative study consisted of semi-structured interviews with all nine of the principal investigators who participated in the idursulfase-IT phase 2\/3 (NCT02055118) and extension (NCT02412787) trials. These investigators enrolled the 56 patients with neuronopathic MPS II who qualified for the extension phase of the trial. The investigators were asked to rate the disease status of their patients. Of the 56 patients, 49 (88%) were rated as having disease that was improved\/improving, stabilized or slowing progression compared with the expected outcomes with no treatment. Three patients were rated as worsening, while the remaining four patients were considered to have slowing progression or worsening disease. Similar results were demonstrated for patients aged from 3 to under 6 years at baseline, with 33 of 39 patients (85%) rated as having disease that was improved\/improving, stabilized or slowing progression. Of the seven patients rated with slowing progression\/worsening or worsening disease, five of them had an<jats:italic>IDS<\/jats:italic>variant other than missense, while two had a missense class variant. All the assigned improved\/improving ratings were in patients receiving idursulfase-IT from the start of the phase 2\/3 trial. Moreover, patients under 3 years of age at baseline were all rated as either improved\/improving or stabilized disease. In a blinded review of patient profiles, investigators were requested to assign a disease status rating to 18 patients with large<jats:italic>IDS<\/jats:italic>deletions; 67% of these patients were rated as improved\/improving or stabilized disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This qualitative analysis provides a snapshot of clinicians\u2019 considerations when evaluating treatment in patients with neuronopathic MPS II, compared with the expected decline in cognitive function in the absence of treatment. The results highlight the importance of robust assessment tools in treatment evaluation.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13023-024-03147-4","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T12:02:08Z","timestamp":1712923328000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical investigator perspectives on patient outcomes in children with neuronopathic mucopolysaccharidosis II during intrathecal idursulfase-IT treatment"],"prefix":"10.1186","volume":"19","author":[{"given":"Karen S.","family":"Yee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Alexanderian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bimpe","family":"Olayinka-Amao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6383-9338","authenticated-orcid":false,"given":"David A. 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For all patients, written informed consent was obtained from the parent(s) or legally authorized guardian(s); assent from the patient was also acquired, if applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"KSY was an employee of Takeda Development Center Americas, Inc. and stockholder of Takeda Pharmaceuticals Company Limited at the time of the analysis (current affiliation is Alexion Pharmaceuticals, Inc., AstraZeneca Rare Disease, Boston, MA, USA). DA was an employee of Takeda Development Center Americas, Inc. and stockholder of Takeda Pharmaceuticals Company Limited at the time of this study and of the writing of the manuscript (current affiliation is Merck). SM and BO-A are employees of RTI Health Solutions, and were contracted by Takeda to perform this analysis. DAHW is an employee of Takeda Development Center Americas, Inc. and stockholders of Takeda Pharmaceuticals Company Limited.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"158"}}