Department of Paediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.
Division of Paediatrics and Perinatology, Tottori University Faculty of Medicine, Tottori, Japan.
Adv Ther. 2023 Apr;40(4):1530-1545. doi: 10.1007/s12325-022-02412-x. Epub 2023 Jan 31.
X-linked hypophosphataemia (XLH) is a rare, genetic renal phosphate-wasting disease, resulting from excess fibroblast growth factor 23 (FGF23) activity, which has a progressive and profound impact on patients throughout life. The monoclonal anti-FGF23 antibody, burosumab, is a subcutaneous injection indicated for the treatment of XLH in children and adults. Originally, burosumab was approved to be administered by a healthcare professional (HCP), but the option of self-administration would enable patient independence and easier access to treatment. Two open-label, single-arm clinical trials, conducted in Japan and Korea, have assessed the safety and efficacy of self-administration of burosumab in both children and adults with XLH.
In KRN23-003 (n = 15 children aged 1-12 years) and KRN23-004 (n = 5 children aged 3-13 years, n = 4 adults aged 21-65 years), children initially received 0.8 mg/kg of burosumab every 2 weeks and adults initially received 1.0 mg/kg of burosumab every 4 weeks. Self-administration was permitted from Week 4, and patients or carers were provided with training to inject correctly.
In both trials, burosumab had an acceptable safety profile with mainly mild-to-moderate adverse events. Following self-administration, no patients reported serious treatment-emergent adverse events ≥ grade 3, injection-site reactions or hypersensitivity reactions related to burosumab. Serum phosphate and active vitamin D levels increased from baseline in children and adults.
These results indicated that the efficacy and safety of burosumab when administered either by a carer or patient are similar to that when administered by an HCP and show that self-administration is a viable option for patients with XLH.
NCT03233126 and NCT04308096.
X 连锁低磷血症（XLH）是一种罕见的遗传性肾脏磷丢失疾病，由成纤维细胞生长因子 23（FGF23）活性过度引起，对患者的生活产生深远而深远的影响。单克隆抗 FGF23 抗体布罗索尤单抗是一种皮下注射剂，用于治疗儿童和成人 XLH。最初，布罗索尤单抗被批准由医疗保健专业人员（HCP）给药，但自我给药的选择将使患者能够独立并更轻松地获得治疗。两项在日本和韩国进行的开放标签、单臂临床试验评估了 XLH 儿童和成人自我给药布罗索尤单抗的安全性和疗效。
在 KRN23-003（n=15 名 1-12 岁儿童）和 KRN23-004（n=5 名 3-13 岁儿童，n=4 名 21-65 岁成人）中，儿童最初每 2 周接受 0.8mg/kg 的布罗索尤单抗，成人最初每 4 周接受 1.0mg/kg 的布罗索尤单抗。从第 4 周开始允许自我给药，并且向患者或护理人员提供了正确注射的培训。
两项试验中，布罗索尤单抗的安全性状况可接受，主要为轻至中度不良事件。自我给药后，没有患者报告严重的治疗后出现的不良事件≥3 级、注射部位反应或与布罗索尤单抗相关的过敏反应。儿童和成人的血清磷和活性维生素 D 水平从基线升高。
这些结果表明，由护理人员或患者给药与由 HCP 给药的布罗索尤单抗的疗效和安全性相似，并且表明自我给药是 XLH 患者的可行选择。
NCT03233126 和 NCT04308096。
