Mobility and Quality of Life in Adults with Paediatric-Onset Hypophosphatasia Treated with Asfotase Alfa: Results from UK Managed Access Agreement

IF 3.4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2025-03-26 DOI:10.1007/s12325-025-03168-w

Katie E. Moss, Richard Keen, Shona Fang, Alexandros Zygouras, Muhammad K. Javaid, Tarekegn Geberhiwot, Kenneth E. S. Poole, Peter Selby, Jennifer S. Walsh, Judith S. Bubbear

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引用次数: 0

Abstract

Introduction

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.

Methods

This prospective, observational data collection included adults with paediatric-onset HPP enroled in the MAA and treated with asfotase alfa for ≥ 6 months to 5 years. 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.

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 m (0.0, 380.0; n = 24) at baseline and improved by 157.3 m (− 171.0, 479.5; n = 16) at month 6; results were sustained throughout follow-up. Median (min, max) Bleck score was 6.0 (2.0, 9.0; n = 24) at baseline and increased to 6.5 (5.0, 9.0; n = 10) at month 36. Median (min, max) aggregate Brief Pain Inventory Short Form severity score was 8.0 (4.3, 10.0; n = 24) at baseline and improved to 4.4 (1.0, 7.8; n = 10) 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 (− 0.26, 0.60; n = 24) at baseline by 0.15 (− 0.36, 0.91; n = 24) 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.

Conclusion

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.

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使用阿斯福通酶 Alfa 治疗儿童发病型低磷血症成人的活动能力和生活质量：英国管理性获取协议的结果。

低磷酸症（HPP）是一种由组织非特异性碱性磷酸酶（ALP）活性不足引起的罕见疾病。Asfotase alfa是一种组织非特异性ALP酶替代疗法，在英国根据管理准入协议（MAA）报销。该分析评估了asfotase在成人HPP患者中的安全性和有效性。方法：这项前瞻性观察性数据收集包括参加MAA并接受asfotase α fa治疗≥6个月至5年的儿科发病HPP成人患者。评估包括活动能力、疼痛和健康相关生活质量（HRQoL），每项评估在第3年定期报告。在整个随访过程中，镇痛药的使用、骨折和兴趣事件（eoi）均被连续报道。结果：在28名接受治疗的成人中，有24人接受了有效性评估。6分钟步行测试中位（min, max）步行距离为172.5 m (0.0, 380.0；N = 24)，提高了157.3 m (- 171.0, 479.5；N = 16)；结果在随访期间持续。Bleck评分中位数（min, max）为6.0 (2.0,9.0；N = 24)，增加到6.5 (5.0,9.0；N = 10)在第36个月。中位（最小，最大）总短期疼痛量表严重程度评分为8.0 (4.3,10.0；N = 24)，改善到4.4 (1.0,7.8；N = 10)在第36个月。在随访期间，8名参与者（33.3%）在随访期间减少或停止使用阿片类药物，4名参与者（16.7%）报告骨折。EQ-5D-3L效用评分中位数（min, max）从0.21 (- 0.26,0.60；N = 24)基线差0.15 (- 0.36,0.91；N = 24)在第6个月，并在整个随访期间相似。注射部位反应是最常见的治疗相关EOI， 17名参与者（60.7%）报告了注射部位反应。三名参与者报告了与治疗相关的严重不良事件。结论：Asfotase治疗可改善活动能力、身体功能、疼痛和HRQoL，且耐受性良好。这些数据表明，asfotase - alfa对儿童发病的成人HPP有益处。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

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.