{
    "abstract": "Hypophosphatasia (HPP) is a rare disease caused by deficient tissue-non-specific alkaline phosphatase (ALP) activity. Asfotase alfa is a tissue-non-specific ALP enzyme-replacement therapy which was reimbursed in the UK under a Managed Access Agreement (MAA). This analysis assessed safety and effectiveness of asfotase alfa in adults with HPP.\nThis prospective, observational data collection included adults with paediatric-onset HPP enroled in the MAA and treated with asfotase alfa for\u00a0\u2265\u00a06\u00a0months to 5\u00a0years. Assessments included mobility, pain, and health-related quality of life (HRQoL), each reported at regular intervals through year 3. Analgesic use, fractures, and events of interest (EOIs) were each reported continuously throughout follow-up.\nOf 28 enroled treated adults, 24 were assessed for effectiveness. Distance walked in the 6-Minute Walk Test was median (min, max) 172.5\u00a0m (0.0, 380.0; n\u00a0=\u00a024) at baseline and improved by 157.3\u00a0m (-\u00a0171.0, 479.5; n\u00a0=\u00a016) at month 6; results were sustained throughout follow-up. Median (min, max) Bleck score was 6.0 (2.0, 9.0; n\u00a0=\u00a024) at baseline and increased to 6.5 (5.0, 9.0; n\u00a0=\u00a010) at month 36. Median (min, max) aggregate Brief Pain Inventory Short Form severity score was 8.0 (4.3, 10.0; n\u00a0=\u00a024) at baseline and improved to 4.4 (1.0, 7.8; n\u00a0=\u00a010) at month 36. During follow-up, 8 participants (33.3%) decreased or discontinued opioid use throughout follow-up and 4 (16.7%) reported fractures. Median (min, max) EQ-5D-3L utility scores improved from 0.21 (-\u00a00.26, 0.60; n\u00a0=\u00a024) at baseline by 0.15 (-\u00a00.36, 0.91; n\u00a0=\u00a024) at month 6 and were similar throughout follow-up. Injection site reactions were the most common treatment-related EOI, reported in 17 participants (60.7%). Three participants reported treatment-related serious adverse events.\nAsfotase alfa treatment improved mobility, physical function, pain, and HRQoL and was well tolerated. These data show the benefit of asfotase alfa in adults with paediatric-onset HPP.\nHypophosphatasia is a rare disease that can cause broken bones, difficulty walking, and pain. Asfotase alfa is a drug that helps correct the underlying cause of hypophosphatasia. The goal of this study was to see if asfotase alfa helps adults in the UK who have had signs and symptoms of hypophosphatasia since childhood to improve their mobility, pain levels, and quality of life. The study also measured any harms that could come from taking asfotase alfa. Participants took asfotase alfa for at least 6\u00a0months and for up to 5\u00a0years. The average age of the 24 participants in the study was 42.5\u00a0years at the start of treatment. Treatment with asfotase alfa led to improvements in the participants\u2019 walking ability and mobility, with effects first observed 6\u201312\u00a0months after starting treatment. Treatment with asfotase alfa also decreased participants\u2019 pain ratings and improved their quality of life after 6\u201312\u00a0months of treatment. Improvements in each of these measures were maintained throughout 5\u00a0years of treatment. Over half of the participants reported skin reactions at the site where asfotase alfa was injected; this was the most common side effect in all participants. The results from this study show that asfotase alfa treatment can help improve the signs and symptoms of hypophosphatasia in adults and that the treatment is generally safe.",
    "authors": [
        {
            "affiliation": "St. George's University Hospitals, Blackshaw Rd, London, SW17 0QT, UK. katie.moss@stgeorges.nhs.uk.",
            "firstname": "Katie E",
            "initials": "KE",
            "lastname": "Moss"
        },
        {
            "affiliation": "Royal National Orthopaedic Hospital, Stanmore, UK.",
            "firstname": "Richard",
            "initials": "R",
            "lastname": "Keen"
        },
        {
            "affiliation": "Alexion, AstraZeneca Rare Disease, Boston, MA, USA.",
            "firstname": "Shona",
            "initials": "S",
            "lastname": "Fang"
        },
        {
            "affiliation": "Alexion, AstraZeneca Rare Disease, London, Middlesex, UK.",
            "firstname": "Alexandros",
            "initials": "A",
            "lastname": "Zygouras"
        },
        {
            "affiliation": "Oxford University, Oxford, UK.",
            "firstname": "Muhammad K",
            "initials": "MK",
            "lastname": "Javaid"
        },
        {
            "affiliation": "Queen Elizabeth Hospital, Birmingham, UK.",
            "firstname": "Tarekegn",
            "initials": "T",
            "lastname": "Geberhiwot"
        },
        {
            "affiliation": "Department of Medicine and NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.",
            "firstname": "Kenneth E S",
            "initials": "KES",
            "lastname": "Poole"
        },
        {
            "affiliation": "Manchester Royal Infirmary, Manchester, UK.",
            "firstname": "Peter",
            "initials": "P",
            "lastname": "Selby"
        },
        {
            "affiliation": "University of Sheffield, Sheffield, UK.",
            "firstname": "Jennifer S",
            "initials": "JS",
            "lastname": "Walsh"
        },
        {
            "affiliation": "Royal National Orthopaedic Hospital, Stanmore, UK.",
            "firstname": "Judith S",
            "initials": "JS",
            "lastname": "Bubbear"
        }
    ],
    "conclusions": "Asfotase alfa treatment improved mobility, physical function, pain, and HRQoL and was well tolerated. These data show the benefit of asfotase alfa in adults with paediatric-onset HPP.",
    "copyrights": "\u00a9 2025. The Author(s).\n\u00a9 2025. The Author(s).",
    "doi": "10.1007/s12325-025-03168-w",
    "journal": "Advances in therapy",
    "keywords": [
        "6-Minute Walk Test",
        "Asfotase alfa",
        "Hypophosphatasia",
        "Quality of life",
        "Rare disease"
    ],
    "methods": null,
    "publication_date": "2025-03-27",
    "pubmed_id": "40138164\n28238808\n29263739\n34215909\n33814268\n14337825\n23858621\n35854311\n19113923\n30975772\n37051203\n27621187\n32654183\n30764793\n30576866\n32987199\n37481150\n32995696\n38459585\n12091180\n10969267\n37118032\n7285447\n31346563\n33579333",
    "results": "Of 28 enroled treated adults, 24 were assessed for effectiveness. Distance walked in the 6-Minute Walk Test was median (min, max) 172.5\u00a0m (0.0, 380.0; n\u00a0=\u00a024) at baseline and improved by 157.3\u00a0m (-\u00a0171.0, 479.5; n\u00a0=\u00a016) at month 6; results were sustained throughout follow-up. Median (min, max) Bleck score was 6.0 (2.0, 9.0; n\u00a0=\u00a024) at baseline and increased to 6.5 (5.0, 9.0; n\u00a0=\u00a010) at month 36. Median (min, max) aggregate Brief Pain Inventory Short Form severity score was 8.0 (4.3, 10.0; n\u00a0=\u00a024) at baseline and improved to 4.4 (1.0, 7.8; n\u00a0=\u00a010) at month 36. During follow-up, 8 participants (33.3%) decreased or discontinued opioid use throughout follow-up and 4 (16.7%) reported fractures. Median (min, max) EQ-5D-3L utility scores improved from 0.21 (-\u00a00.26, 0.60; n\u00a0=\u00a024) at baseline by 0.15 (-\u00a00.36, 0.91; n\u00a0=\u00a024) at month 6 and were similar throughout follow-up. Injection site reactions were the most common treatment-related EOI, reported in 17 participants (60.7%). Three participants reported treatment-related serious adverse events.",
    "title": "Mobility and Quality of Life in Adults with Paediatric-Onset Hypophosphatasia Treated with Asfotase Alfa: Results from UK Managed Access Agreement.",
    "xml": "<Element 'PubmedArticle' at 0x78850342b600>"
}