Continued Beneficial Effects of Burosumab in Adults with X-Linked Hypophosphatemia: Results from a 24-Week Treatment Continuation Period After a 24-Week Double-Blind Placebo-Controlled Period
Continued Beneficial Effects of Burosumab in Adults with X-Linked Hypophosphatemia: Results from a 24-Week Treatment Continuation Period After a 24-Week Double-Blind Placebo-Controlled Period
复制标题
DOI：
10.1007/s00223-019-00568-3
复制
发表时间：
2019-09-01
影响因子：
4.2
通讯作者：
Insogna, Karl
中科院分区：
文献类型：
--
作者：
Portale, Anthony A.;Carpenter, Thomas O.;Insogna, Karl
Burosumab是一种针对FGF 23的全人源单克隆抗体，是唯一获批用于治疗X连锁低磷血症（XLH）的药物，XLH是一种罕见的遗传性疾病，其特征为肾磷酸盐消耗和大量累积性肌肉骨骼发病率。在最初的24周随机对照试验中，134例XLH成人患者每4周一次接受burosumab 1 mg/kg（n = 68）或安慰剂（n = 66）。24周后，所有受试者均接受开放标签burosumab治疗，直至第48周。本报告描述了开放标签治疗期间burosumab的疗效和安全性。从第24-48周开始，83.8%的接受burosumab治疗的受试者的血清磷浓度保持正常，89.4%的接受burosumab治疗的受试者在安慰剂治疗后恢复正常。到第48周，burosumab组63.1%的基线骨折/假性骨折完全愈合，而安慰剂组为35.2%。在两组中，从基线到第48周，患者报告的僵硬、疼痛、身体功能和6分钟内行走的总距离评分均出现临床显著和持续改善。未发生致死性不良事件或治疗相关严重不良事件。在第24周或第48周，肾钙质沉着症评分相对于基线的变化均未超过一个等级。这些数据表明，在XLH受试者中，burosumab持续治疗耐受性良好，可持续纠正血清磷水平，骨折和假性骨折持续愈合，关键肌肉骨骼损伤持续改善。
Burosumab, a fully human monoclonal antibody to FGF23, is the only approved treatment for X-linked hypophosphatemia (XLH), a rare genetic disorder characterized by renal phosphate wasting and substantial cumulative musculoskeletal morbidity. During an initial 24-week randomized, controlled trial, 134 adults with XLH received burosumab 1 mg/kg (n = 68) or placebo (n = 66) every 4 weeks. After 24 weeks, all subjects received open-label burosumab until week 48. This report describes the efficacy and safety of burosumab during the open-label treatment period. From weeks 24-48, serum phosphorus concentrations remained normal in 83.8% of participants who received burosumab throughout and were normalized in 89.4% who received burosumab after placebo. By week 48, 63.1% of baseline fractures/pseudofractures healed fully with burosumab, compared with 35.2% with burosumab after placebo. In both groups, burosumab was associated with clinically significant and sustained improvement from baseline to week 48 in scores for patient-reported outcomes of stiffness, pain, physical function, and total distance walked in 6 min. Rates of adverse events were similar for burosumab and placebo. There were no fatal adverse events or treatment-related serious adverse events. Nephrocalcinosis scores did not change from baseline by more than one grade at either week 24 or 48. These data demonstrate that in participants with XLH, continued treatment with burosumab is well tolerated and leads to sustained correction of serum phosphorus levels, continued healing of fractures and pseudofractures, and sustained improvement in key musculoskeletal impairments.