Raja Padidela, Nick Bishop, Paul Arundel, Shona Fang, Alexandros Zygouras, M Zulf Mughal, Nick Shaw, Vrinda Saraff
{"title":"用Asfotase Alfa治疗儿科发病磷酸酶减少症儿童的活动能力和生活质量：来自英国管理准入协议的结果","authors":"Raja Padidela, Nick Bishop, Paul Arundel, Shona Fang, Alexandros Zygouras, M Zulf Mughal, Nick Shaw, Vrinda Saraff","doi":"10.1007/s12325-025-03225-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Hypophosphatasia (HPP) is a rare, inherited metabolic bone disease with a high degree of morbidity and mortality in children. Asfotase alfa is an enzyme replacement therapy for HPP reimbursed in the UK since 2017 under a Managed Access Agreement (MAA). This analysis assessed the effectiveness and safety of asfotase alfa in children < 18 years of age.</p><p><strong>Methods: </strong>The MAA was a prospective, longitudinal data collection in children with paediatric-onset HPP. Effectiveness outcomes were evaluated in children who were treated with asfotase alfa for ≥ 6 months. Data were collected on respiratory support, growth, mobility, motor development, analgesic use, quality of life, and safety at enrolment and throughout the 5-year MAA.</p><p><strong>Results: </strong>Twenty-four children enrolled in the MAA and 20 were included in the analysis. Twelve children had received asfotase alfa before enrolment through a clinical trial or compassionate use program. From baseline to month 60, the median (minimum, maximum) change in height and weight Z-scores were 0.20 (- 0.9, 1.2; n = 6) and - 0.5 (- 1.9, 1.5; n = 6), respectively. The median (minimum, maximum) percent of predicted distance walked in the 6-Minute Walk Test increased by 3.8% (- 8.6, 4.3; n = 5) at month 3 and was sustained through follow-up. Median (minimum, maximum) child- and parent-reported Pediatric Quality of Life Inventory scores were 59.2 (15.2, 91.3; n = 11) and 53.4 (16.3, 100.0; n = 18) at baseline and increased by 21.7 (5.4, 37.0; n = 3) and 16.3 (9.8, 45.7; n = 4) at month 60, respectively. Treatment-naïve children had a greater clinical response than treatment-experienced participants, who maintained their status. No deaths occurred in the study. The most common adverse events were injection site reactions, reported in 8/24 participants (33.3%).</p><p><strong>Conclusion: </strong>This analysis confirmed the clinical benefit of asfotase alfa in children with HPP. Asfotase alfa was well tolerated, with no new safety signals identified.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mobility and Quality of Life in Children with Paediatric-Onset Hypophosphatasia Treated with Asfotase Alfa: Results from UK Managed Access Agreement.\",\"authors\":\"Raja Padidela, Nick Bishop, Paul Arundel, Shona Fang, Alexandros Zygouras, M Zulf Mughal, Nick Shaw, Vrinda Saraff\",\"doi\":\"10.1007/s12325-025-03225-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Hypophosphatasia (HPP) is a rare, inherited metabolic bone disease with a high degree of morbidity and mortality in children. Asfotase alfa is an enzyme replacement therapy for HPP reimbursed in the UK since 2017 under a Managed Access Agreement (MAA). This analysis assessed the effectiveness and safety of asfotase alfa in children < 18 years of age.</p><p><strong>Methods: </strong>The MAA was a prospective, longitudinal data collection in children with paediatric-onset HPP. Effectiveness outcomes were evaluated in children who were treated with asfotase alfa for ≥ 6 months. Data were collected on respiratory support, growth, mobility, motor development, analgesic use, quality of life, and safety at enrolment and throughout the 5-year MAA.</p><p><strong>Results: </strong>Twenty-four children enrolled in the MAA and 20 were included in the analysis. Twelve children had received asfotase alfa before enrolment through a clinical trial or compassionate use program. From baseline to month 60, the median (minimum, maximum) change in height and weight Z-scores were 0.20 (- 0.9, 1.2; n = 6) and - 0.5 (- 1.9, 1.5; n = 6), respectively. The median (minimum, maximum) percent of predicted distance walked in the 6-Minute Walk Test increased by 3.8% (- 8.6, 4.3; n = 5) at month 3 and was sustained through follow-up. Median (minimum, maximum) child- and parent-reported Pediatric Quality of Life Inventory scores were 59.2 (15.2, 91.3; n = 11) and 53.4 (16.3, 100.0; n = 18) at baseline and increased by 21.7 (5.4, 37.0; n = 3) and 16.3 (9.8, 45.7; n = 4) at month 60, respectively. Treatment-naïve children had a greater clinical response than treatment-experienced participants, who maintained their status. No deaths occurred in the study. The most common adverse events were injection site reactions, reported in 8/24 participants (33.3%).</p><p><strong>Conclusion: </strong>This analysis confirmed the clinical benefit of asfotase alfa in children with HPP. 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Mobility and Quality of Life in Children with Paediatric-Onset Hypophosphatasia Treated with Asfotase Alfa: Results from UK Managed Access Agreement.
Introduction: Hypophosphatasia (HPP) is a rare, inherited metabolic bone disease with a high degree of morbidity and mortality in children. Asfotase alfa is an enzyme replacement therapy for HPP reimbursed in the UK since 2017 under a Managed Access Agreement (MAA). This analysis assessed the effectiveness and safety of asfotase alfa in children < 18 years of age.
Methods: The MAA was a prospective, longitudinal data collection in children with paediatric-onset HPP. Effectiveness outcomes were evaluated in children who were treated with asfotase alfa for ≥ 6 months. Data were collected on respiratory support, growth, mobility, motor development, analgesic use, quality of life, and safety at enrolment and throughout the 5-year MAA.
Results: Twenty-four children enrolled in the MAA and 20 were included in the analysis. Twelve children had received asfotase alfa before enrolment through a clinical trial or compassionate use program. From baseline to month 60, the median (minimum, maximum) change in height and weight Z-scores were 0.20 (- 0.9, 1.2; n = 6) and - 0.5 (- 1.9, 1.5; n = 6), respectively. The median (minimum, maximum) percent of predicted distance walked in the 6-Minute Walk Test increased by 3.8% (- 8.6, 4.3; n = 5) at month 3 and was sustained through follow-up. Median (minimum, maximum) child- and parent-reported Pediatric Quality of Life Inventory scores were 59.2 (15.2, 91.3; n = 11) and 53.4 (16.3, 100.0; n = 18) at baseline and increased by 21.7 (5.4, 37.0; n = 3) and 16.3 (9.8, 45.7; n = 4) at month 60, respectively. Treatment-naïve children had a greater clinical response than treatment-experienced participants, who maintained their status. No deaths occurred in the study. The most common adverse events were injection site reactions, reported in 8/24 participants (33.3%).
Conclusion: This analysis confirmed the clinical benefit of asfotase alfa in children with HPP. Asfotase alfa was well tolerated, with no new safety signals identified.
期刊介绍：
Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
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