Martín Ramos Silvia, Gil-Calvo Marta, Roldán Virginia, Castellano Martínez Ana, Santos Fernando
Hospital Universitario Central de Asturias, Oviedo, Spain.
Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain.
Front Pediatr. 2020 Feb 18;8:48. doi: 10.3389/fped.2020.00048. eCollection 2020.
X-linked hypophosphatemia (XLH) causes significant burden in pediatric patients in spite of maintained treatment with phosphate supplements and vitamin D derivatives. Administration of burosumab has shown promising results in clinical trial but studies assessing its effect in the everyday practice are missing. With this aim, we analyzed the response to one-year treatment with burosumab, injected subcutaneously at 0.8 mg/kg every 2 weeks, in five children (three females) aged from 6 to 16 years, with genetically confirmed XLH. Patients were being treated with phosphate and vitamin D analogs until the beginning of burosumab treatment. In all children, burosumab administration led to normalization of serum phosphate in association with marked increase of tubular reabsorption of phosphate and reduction of elevated serum alkaline phosphatase levels. Baseline height of patients, from -3.56 to -0.46 SD, increased in the three prepubertal children (+0.84, +0.89, and +0.16 SD) during burosumab treatment. Growth improvement was associated with reduction in body mass index (-1.75, -1.47, and -0.17 SD, respectively), suggesting a salutary effect of burosumab on physical activity and body composition. Burosumab was well-tolerated, mild local pain at the injection site and transient and mild headache following the initial doses of burosumab being the only reported undesirable side effects. No patient exhibited hyperphosphatemia, progression of nephrocalcinosis, worsening of metabolic control or developed hyperparathyroidism. Mild elevation of serum PTH present at the beginning of treatment in one patient 4 was not modified by burosumab administration. These results indicate that in the clinical setting, beyond the strict conditions and follow-up of clinical trials, burosumab treatment for 1 year exerts positive effects in pediatric patients with XLH without major adverse events.
尽管接受了磷酸盐补充剂和维生素D衍生物的持续治疗，X连锁低磷血症（XLH）仍给儿科患者带来了沉重负担。布罗索尤单抗的给药在临床试验中显示出了有前景的结果，但缺乏评估其在日常临床实践中效果的研究。出于这个目的，我们分析了5名年龄在6至16岁、经基因确诊为XLH的儿童（3名女性）对布罗索尤单抗进行为期一年治疗的反应，布罗索尤单抗每2周皮下注射一次，剂量为0.8mg/kg。在开始布罗索尤单抗治疗前，患者一直在接受磷酸盐和维生素D类似物治疗。在所有儿童中，布罗索尤单抗的给药使血清磷酸盐正常化，同时伴有肾小管对磷酸盐重吸收的显著增加以及血清碱性磷酸酶水平的降低。3名青春期前儿童在接受布罗索尤单抗治疗期间，基线身高从-3.56至-0.46标准差增加（分别为+0.84、+0.89和+0.16标准差）。生长改善与体重指数降低相关（分别为-1.75、-1.47和-0.17标准差），提示布罗索尤单抗对身体活动和身体成分有有益影响。布罗索尤单抗耐受性良好，唯一报告的不良副作用是注射部位轻度局部疼痛以及初始剂量布罗索尤单抗后短暂且轻度的头痛。没有患者出现高磷血症、肾钙质沉着症进展、代谢控制恶化或发生甲状旁腺功能亢进。1名患者4在治疗开始时出现的血清甲状旁腺激素轻度升高未因布罗索尤单抗的给药而改变。这些结果表明，在临床环境中，除了临床试验的严格条件和随访外，布罗索尤单抗治疗1年对患有XLH的儿科患者具有积极作用，且无重大不良事件。
