Namba Noriyuki, Kubota Takuo, Muroya Koji, Tanaka Hiroyuki, Kanematsu Masanori, Kojima Masahiro, Orihara Shunichiro, Kanda Hironori, Seino Yoshiki, Ozono Keiichi
Division of Pediatrics and Perinatology, Tottori University Faculty of Medicine, Yonago, Tottori, 683-8504, Japan.
Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
J Endocr Soc. 2022 Feb 11;6(5):bvac021. doi: 10.1210/jendso/bvac021. eCollection 2022 May 1.
Burosumab, an anti-fibroblast growth factor 23 antibody, was recently approved for the treatment of X-linked hypophosphatemia (XLH).We evaluated the safety and efficacy of burosumab in pediatric XLH patients.
This open-label, phase 3/4 trial of ≤ 124 weeks' duration was conducted at 4 Japanese medical centers. Fifteen children aged 1 to 12 years with XLH were included. All had previously been treated with phosphorus or vitamin D. Subcutaneous burosumab was administered every 2 weeks, starting with 0.8 mg/kg, and adjusted based on serum phosphorus levels and any safety concerns (maximum 2 mg/kg). Safety assessments included the frequency of treatment-emergent adverse events (TEAEs). Efficacy of burosumab on biochemical markers, clinical markers of rickets, motor function, and growth was also evaluated.
The average treatment duration was 121.7 weeks. Frequently reported TEAEs were nasopharyngitis (46.7%), dental caries (40.0%), and influenza (33.3%). At baseline, patients had low serum phosphorus concentrations (2.6 ± 0.3 mg/dL) and low-to-normal 1,25-dihydroxyvitamin D concentrations (24.7 ± 12.7 pg/mL), which increased with burosumab treatment and were maintained during the study period. Alkaline phosphatase decreased continuously. At baseline, the mean ± SD total Thacher Rickets Severity Score (RSS) was 1.3 ± 1.2, and 4 patients (26.7%) had an RSS ≥ 2.0. Mean Radiographic Global Impression of Change and RSS tended to improve, particularly in patients with higher baseline RSS. There was a trend toward increased 6-minute walk test distance. No apparent changes in growth rate were observed.
Burosumab has a good safety profile and is effective in pediatric patients with XLH.
布罗索尤单抗是一种抗成纤维细胞生长因子23抗体，最近被批准用于治疗X连锁低磷血症（XLH）。我们评估了布罗索尤单抗在儿童XLH患者中的安全性和疗效。
这项为期≤124周的开放标签3/4期试验在4家日本医疗中心进行。纳入了15名1至12岁的XLH儿童。所有患儿此前均接受过磷或维生素D治疗。皮下注射布罗索尤单抗，每2周一次，起始剂量为0.8 mg/kg，并根据血清磷水平和任何安全性问题进行调整（最大剂量2 mg/kg）。安全性评估包括治疗期间出现的不良事件（TEAE）的发生率。还评估了布罗索尤单抗对生化指标、佝偻病临床指标、运动功能和生长的疗效。
平均治疗时长为121.7周。常见的TEAE包括鼻咽炎（46.7%）、龋齿（40.0%）和流感（33.3%）。基线时，患者血清磷浓度较低（2.6±0.3 mg/dL），1,25 - 二羟维生素D浓度处于低至正常水平（24.7±12.7 pg/mL），随着布罗索尤单抗治疗升高，并在研究期间维持稳定。碱性磷酸酶持续下降。基线时，平均±标准差的总撒切尔佝偻病严重程度评分（RSS）为1.3±1.2，4例患者（26.7%）的RSS≥2.0。平均放射学整体变化印象和RSS有改善趋势，尤其是基线RSS较高的患者。6分钟步行试验距离有增加趋势。未观察到生长速率有明显变化。
布罗索尤单抗安全性良好，对儿童XLH患者有效。
