布罗索尤单抗治疗X连锁低磷性佝偻病临床分析

doi:10.12372/jcp.2025.24e0813

Abstract

Abstract:

Objective To summarize the efficacy and safety of burosumab in the treatment of X-linked hypophosphatemic rickets (XLH). Methods The clinical data of a child hospitalized in the Department of Endocrinology and Metabolism in August 2022 who was treated with burosumab for XLH due to PHEX gene variation were retrospectively analyzed, and the relevant literature was reviewed. Results A 5 years and 11 months old boy was treated for "malformation of both lower limbs for 3 years with bone pain for 2 months". The blood phosphorus value at admission was 0.82 mmol/L. The X-ray examination of the bones showed cup-shaped and brush-like changes at the epiphysis of the long bones, and the changes in all the bones were consistent with the symptoms of rickets. The mother of the child had symptoms of short stature, malformation of both lower limbs with bone pain. The genetic testing found a variation of c.1282C > T, p.Gln428* in the PHEX gene in the child, which came from his mother. After treatment with burosumab, blood phosphorus value was increased, alkaline phosphatase and parathyroid hormone levels were decreased, growth rate was increased, bone pain was improved, activity tolerance was improved, bone deformities were significantly improved, and no drug-related adverse reactions occurred. Conclusions Burosumab can be used for the treatment of children with XLH due to PHEX gene variation, and it can improve several indicators and has good safety.

Key words: burosumab, X-linked hypophosphatemic rickets, PHEX gene, hypophosphatemia, child

YANG Fan, LI Juan, ZHANG Wanglin, CHANG Guoying, LI Xin, LI Yunyun, SHE Jiaxiao, LIN Kana, LI Hao, WANG Xiumin. Clinical analysis of burosumab in the treatment of X-linked hypophosphatemic rickets[J].Journal of Clinical Pediatrics, 2025, 43(2): 105-111.

Figures/Tables 5

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Tab 1

Summary of data from a 64-week clinical trial of brosozumab for children with hypophosphatemic rickets"

项目	Whyte等^[7] (n=13)	Carpenter等^[8-9] (n=52)		Imel 等^[10] (n=61)		Namba等^[11] (n=15)
临床研究试验号	NCT02750618	NCT02163577		NCT02915705		NCT03233126
入组时年龄/岁	1~4	5~12		1~12		1~12
例数	13	26	26	29	32	15
布罗索尤单抗使用剂量和间隔时间	0.8~1.2 mg/kg，Q2W	初始0.1 mg/kg，滴定至平均0.98 mg/kg，Q2W	初始0.2 mg/kg，滴定至平均1.5 mg/kg，Q4W	0.8~1.2 mg/kg，Q2W	磷酸盐和活性维生素D	初始0.8mg/kg，最大2mg/kg，Q2W
有效指标
血磷升高均值/mg·dL^-1	0.89	0.84		0.92	0.20	0.90²⁾
1,25(OH)₂D₃升高均值/pg·mL^-1	13	18		30	18	35.3²⁾
基线RSS( x±s)	2.9±1.4	1.9±1.2	1.7±1.0	3.2±1.0	3.2±1.1	1.3±1.2
第64周时RSS ( x±s)	0.9±0.5²⁾	0.8±0.6	0.9±0.5	1.0±0.7²⁾	2.2±0.8²⁾	0.6±0.3²⁾
RSS较基线变化LS均值(SE)	-2.0(0.1)	-1.00(0.11)	-0.84(0.10)	-2.2(0.1)	-1.0(0.2)	-0.7²⁾
第64周时总体RGI-C均值(SE)	+2.2(0.1)	+1.56(0.11)	+1.58(0.11)	+2.1(0.1)	+1.0(0.1)	+1.7³⁾
第64周时总体RGI-C/%	100	58	50	87	19	未提及
第64周时下肢畸形RGI-C均值(SE)	+1.6(0.1)	+0.5(0.1)¹⁾		+1.3(0.2)	+0.3(0.1)	未提及
安全指标
所有不良反应[n(%)]	13(100)	26(100)		29(100)	27(84.4)	15(100)
与布罗索尤单抗有关的不良反应[n(%)]	5(38.5)	0	0	0	0	2(13.3)
导致停药或死亡的不良反应[n(%)]	0	0	0	0	0	0
最常见不良反应(≥30%)	咳嗽、发热、上呼吸道感染、牙齿脓肿、鼻涕、呕吐、鼻塞、腹泻、四肢疼痛、链球菌性咽炎、注射部位反应、过敏	注射部位反应、头痛、咳嗽、鼻咽炎、肢体疼痛、上呼吸道感染、呕吐和发热	注射部位反应、头痛、咳嗽、鼻咽炎、四肢疼痛、上呼吸道感染、呕吐、关节痛、发热、季节性过敏	发热、注射部位反应、咳嗽、关节痛、呕吐、鼻咽炎、超敏反应、肢体疼痛、头痛、注射部位红斑、龋齿		鼻咽炎、龋齿、流感、中耳炎、咽炎和上呼吸道感染
最常见药物相关不良反应(≥20%)	注射部位红斑和肢体疼痛	无	无	无	无	无

Tab 1

References 20

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Clinical analysis of burosumab in the treatment of X-linked hypophosphatemic rickets

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