Khan Aliya A, Rush Eric T, Wakeford Craig, Staub Daniel, Brandi Maria Luisa
McMaster University, Hamilton, ON, Canada.
Children's Mercy Kansas City, Kansas City, MO, USA.
Adv Ther. 2025 Jul 25. doi: 10.1007/s12325-025-03309-1.
First reported in 1948, hypophosphatasia (HPP) is a rare systemic disease caused by deficient activity of tissue-nonspecific alkaline phosphatase (ALP) enzyme. Patients with HPP experience skeletal and dental manifestations such as rickets/osteomalacia, fractures, pseudofractures, and premature tooth loss, as well as nonskeletal symptoms such as pain and muscle weakness, which result in impaired mobility and poor quality of life. For decades, no specific treatment was available for HPP and the disease was often fatal in infants. Asfotase alfa is a tissue-nonspecific ALP enzyme replacement therapy (ERT) that received first regulatory approval in 2015 in Japan, the European Union, and the United States for the treatment of HPP. This review draws from clinical trial findings, real-world evidence, and relevant case study data demonstrating the safety and effectiveness of asfotase alfa in improving a broad range of skeletal and nonskeletal manifestations in both pediatric and adult patients. Asfotase alfa has been shown to be well tolerated, with manageable side effects. Further, asfotase alfa treatment has improved survival and respiratory outcomes, skeletal outcomes, physical and motor function, pain, disability, and quality of life in patients with HPP. This evidence-based review aims to generate a foundation for improving the understanding of disease pathophysiology, hence enhancing the effectiveness of ERT in patients with HPP.
低磷性骨软化症（HPP）于1948年首次报道，是一种由组织非特异性碱性磷酸酶（ALP）活性缺乏引起的罕见全身性疾病。HPP患者会出现骨骼和牙齿方面的表现，如佝偻病/骨软化症、骨折、假性骨折和过早掉牙，以及疼痛和肌肉无力等非骨骼症状，这些症状会导致行动能力受损和生活质量下降。几十年来，HPP没有特效治疗方法，该病在婴儿中往往是致命的。阿法骨化醇是一种组织非特异性ALP酶替代疗法（ERT），于2015年在日本、欧盟和美国首次获得监管批准，用于治疗HPP。本综述借鉴了临床试验结果、真实世界证据和相关案例研究数据，证明了阿法骨化醇在改善儿童和成人患者广泛的骨骼和非骨骼表现方面的安全性和有效性。阿法骨化醇已被证明耐受性良好，副作用可控。此外，阿法骨化醇治疗改善了HPP患者的生存率和呼吸结局、骨骼结局、身体和运动功能、疼痛、残疾状况以及生活质量。这项基于证据的综述旨在为增进对疾病病理生理学的理解奠定基础，从而提高ERT对HPP患者的疗效。
