Padidela Raja, Bishop Nick, Arundel Paul, Fang Shona, Zygouras Alexandros, Mughal M Zulf, Shaw Nick, Saraff Vrinda
Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, M13 9WL, UK.
Faculty of Biology Medicine and Health, University of Manchester and Manchester Academic Health Science Centre, Manchester, UK.
Adv Ther. 2025 May 29. doi: 10.1007/s12325-025-03225-4.
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.
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.
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%).
This analysis confirmed the clinical benefit of asfotase alfa in children with HPP. Asfotase alfa was well tolerated, with no new safety signals identified.
低磷酸酯酶症（HPP）是一种罕见的遗传性代谢性骨病，在儿童中具有较高的发病率和死亡率。阿加糖酶α是一种用于治疗HPP的酶替代疗法，自2017年起在英国根据管理准入协议（MAA）获得报销。本分析评估了阿加糖酶α在18岁以下儿童中的有效性和安全性。
MAA是一项针对儿童期发病的HPP患儿的前瞻性纵向数据收集研究。对接受阿加糖酶α治疗≥6个月的儿童进行有效性评估。在入组时以及整个5年的MAA期间收集有关呼吸支持、生长、活动能力、运动发育、镇痛药物使用、生活质量和安全性的数据。
24名儿童入组MAA，其中20名纳入分析。12名儿童在入组前通过临床试验或同情用药计划接受过阿加糖酶α治疗。从基线到第60个月，身高和体重Z评分的中位数（最小值，最大值）变化分别为0.20（-0.9，1.2；n = 6）和-0.5（-1.9，1.5；n = 6）。在6分钟步行试验中，预测步行距离的中位数（最小值，最大值）百分比在第3个月增加了3.8%（-8.6，4.3；n = 5），并在随访期间保持。基线时儿童和家长报告的儿童生活质量量表评分的中位数（最小值，最大值）分别为59.2（15.2，91.3；n = 11）和53.4（16.3，100.0；n = 18），在第60个月分别增加了21.7（5.4，37.0；n = 3）和16.3（9.8，45.7；n = 4）。未接受过治疗的儿童比有治疗经验的参与者有更大的临床反应，后者维持了其状态。研究中未发生死亡。最常见的不良事件是注射部位反应，24名参与者中有8名（33.3%）报告了该反应。
本分析证实了阿加糖酶α对HPP儿童的临床益处。阿加糖酶α耐受性良好，未发现新的安全信号。
