Burosumab Therapy in Children with X-Linked Hypophosphatemia
Burosumab Therapy in Children with X-Linked Hypophosphatemia
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DOI：
10.1056/nejmoa1714641
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发表时间：
2018-05-24
影响因子：
158.5
通讯作者：
Portale, Anthony A.
中科院分区：
文献类型：
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作者：
Carpenter, Thomas O.;Whyte, Michael P.;Portale, Anthony A.
GROUNDX相关的低磷酸盐血症的特征是成纤维细胞生长因子23（FGF-23）分泌增加，导致低磷酸盐血症，从而导致佝偻病、骨软化和骨骼畸形。我们调查了burosum，一种单克隆抗体，目标FGF-23，在患者与X连锁hypophosphatemia. METHODS在一个开放标签，2期试验，我们随机分配52名儿童与X连锁hypophosphatemia，在1：1的比例，接受皮下burosum每2周或每4周，剂量进行调整，以达到血清磷水平在正常范围的低端。主要终点是Thacher佝偻病严重程度总评分从基线到第40周和第64周的变化（范围从0到10，评分越高表明疾病严重程度越大）。此外，使用影像学总体印象变化评价从基线至第40周和至第64周的佝偻病变化。其他终点是药效学标志物、线性生长、体能和患者报告的结果的变化以及不良事件的发生率。
BACKGROUNDX-linked hypophosphatemia is characterized by increased secretion of fibroblast growth factor 23 (FGF-23), which leads to hypophosphatemia and consequently rickets, osteomalacia, and skeletal deformities. We investigated burosumab, a monoclonal antibody that targets FGF-23, in patients with X-linked hypophosphatemia.METHODSIn an open-label, phase 2 trial, we randomly assigned 52 children with X-linked hypophosphatemia, in a 1: 1 ratio, to receive subcutaneous burosumab either every 2 weeks or every 4 weeks; the dose was adjusted to achieve a serum phosphorus level at the low end of the normal range. The primary end point was the change from baseline to weeks 40 and 64 in the Thacher rickets severity total score (ranging from 0 to 10, with higher scores indicating greater disease severity). In addition, the Radiographic Global Impression of Change was used to evaluate rachitic changes from baseline to week 40 and to week 64. Additional end points were changes in pharmacodynamic markers, linear growth, physical ability, and patient-reported outcomes and the incidence of adverse events.RESULTSThe mean Thacher rickets severity total score decreased from 1.9 at baseline to 0.8 at week 40 with every-2-week dosing and from 1.7 at baseline to 1.1 at week 40 with every-4-week dosing (P