{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:37:09Z","timestamp":1790858229898,"version":"4.1.0"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T00:00:00Z","timestamp":1709856000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T00:00:00Z","timestamp":1709856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100006396","name":"Alexion Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006396","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Hypophosphatasia (HPP) is a rare inherited disease caused by deficient activity of tissue-nonspecific alkaline phosphatase. Many adults with HPP have a high burden of disease, experiencing chronic pain, fatigue, limited mobility, and dental issues, contributing to decreased health-related quality of life (HRQoL). HPP may be treated with the enzyme replacement therapy asfotase alfa though real-world data in adults are limited. This analysis was conducted to assess the clinical effectiveness of asfotase alfa among adults in the Global HPP Registry.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The Global HPP Registry is an observational, prospective, multinational study. Adults\u2009\u2265\u200918\u00a0years of age were included in this analysis if they had serum alkaline phosphatase (ALP) activity below the age- and sex-adjusted reference ranges, and\/or <jats:italic>ALPL<\/jats:italic> variant(s), and received asfotase alfa for\u2009\u2265\u20096\u00a0months. Mobility was assessed with the 6-Minute Walk Test (6MWT), and patient-reported outcomes tools were used to assess pain (Brief Pain Inventory-Short Form), quality of life (36-item\u00a0Short Form Health Survey, version 2 [SF-36v2]), and disability (Health Assessment Questionnaire-Disability Index) at multiple time points from baseline through Month 36. Data were collected as per usual standard of care; patients may not have contributed data at all time points.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A total of 190 patients met the inclusion criteria. For patients with\u2009\u2265\u20091 follow-up measurement, the mean distance achieved on 6MWT increased from 404\u00a0m (range 60\u2013632\u00a0m) at baseline (n\u2009=\u200931) to 484\u00a0m at Month 12 (range 240\u2013739\u00a0m; n\u2009=\u200918) and remained above baseline through Month 36 (n\u2009=\u20097). Improvements in mean self-reported pain severity scores ranged from\u2009\u2212\u20090.72 (95% CI:\u2009\u2212\u20091.23,\u2009\u2212\u20090.21; n\u2009=\u200938) to\u2009\u2212\u20091.13 (95% CI:\u2009\u2212\u20091.76,\u2009\u2212\u20090.51; n\u2009=\u200926) and were observed at all time points. Improvements in the Physical Component Summary score of SF-36v2 were achieved by Month 6 and sustained throughout follow-up. There was a trend toward improvement in the Mental Component Summary\u00a0score of SF-36v2 at most time points, with considerable fluctuations from Months 12 (n\u2009=\u200928) through 36 (n\u2009=\u200921).\u00a0The most frequent adverse events were injection\u00a0site reactions.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Adults with HPP who received asfotase alfa for\u2009\u2265\u20096\u00a0months experienced improvements in mobility, physical function, and HRQoL, which were maintained over 3\u00a0years of follow-up.<\/jats:p>\n                <jats:p>Registration: NCT02306720; EUPAS13514.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-024-03048-6","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T12:01:46Z","timestamp":1709899306000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Effectiveness of asfotase alfa for treatment of adults with hypophosphatasia: results from a global registry"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8251-909X","authenticated-orcid":false,"given":"Priya S.","family":"Kishnani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel \u00c1ngel","family":"Martos-Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Linglart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Petryk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Messali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shona","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Rockman-Greenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Ozono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"H\u00f6gler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lothar","family":"Seefried","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn M.","family":"Dahir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,8]]},"reference":[{"key":"3048_CR1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.bone.2017.02.011","volume":"102","author":"MP Whyte","year":"2017","unstructured":"Whyte MP. 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The protocol for the registry was approved by the institutional review board (or equivalent) at each participating site and is being conducted in accordance with European Medicines Agency Good Pharmacovigilance Practices, International Society for Pharmacoepidemiology Guidelines for Good Pharmacoepidemiology Practices, and the Declaration of Helsinki. All patients or parent\/legal guardians provided written informed consent and approval to release medical records for inclusion in the registry.","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":"PSK, KMD, GAMM, AL, CRG, KO, WH, and LS consult for\/have received research funding\/honoraria from Alexion, AstraZeneca Rare Disease. AP, AM, and SF are employees of and may own stock\/options in Alexion, AstraZeneca Rare Disease. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"109"}}