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

临床儿科杂志 ›› 2025, Vol. 43 ›› Issue (2): 105-111.doi: 10.12372/jcp.2025.24e0813

布罗索尤单抗治疗X连锁低磷性佝偻病临床分析

杨帆¹^,^*, 李娟²^,^*, 张网林³, 常国营¹^,², 李辛², 李芸芸¹, 佘佳笑, 林卡娜¹, 李浩¹, 王秀敏¹^,²()

1.上海交通大学医学院附属上海儿童医学中心临床研究病房骨科（上海 200127）
2.上海交通大学医学院附属上海儿童医学中心内分泌遗传代谢科（上海 200127）
3.上海交通大学医学院附属上海儿童医学中心骨科（上海 200127）

收稿日期:2024-08-12 录用日期:2024-11-28 出版日期:2025-02-15 发布日期:2025-02-12
通讯作者: 王秀敏电子信箱：wangxiumin1019@126.com
作者简介:^*具有同等贡献
基金资助:
上海市“科技创新行动计划”医学创新研究专项(20MC1920400);浦东新区卫健委联合攻关项目(PW2021D-13);2024年医疗服务与保障能力提升（国家临床重点专科建设）项目(10000015Z155080000004)

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

YANG Fan¹^,^*, LI Juan²^,^*, ZHANG Wanglin³, CHANG Guoying¹^,², LI Xin², LI Yunyun¹, SHE Jiaxiao, LIN Kana¹, LI Hao¹, WANG Xiumin¹^,²()

1. Clinical Research Ward, Clinical Research Center, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
2. Department of Endocrinology and Metabolism, Clinical Research Center, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
3. Department of Orthopedics, Clinical Research Center, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China

Received:2024-08-12 Accepted:2024-11-28 Published:2025-02-15 Online:2025-02-12

摘要/Abstract

摘要：

目的总结布罗索尤单抗治疗X连锁低磷性佝偻病（XLH）的疗效和安全性。方法回顾性分析2022年8月于内分泌代谢科住院，采用布罗索尤单抗治疗因PHEX基因变异导致XLH的1例患儿的临床资料，并进行相关文献复习。结果患儿，男，5岁11月龄，因“双下肢畸形3年，伴骨痛2个月”就诊。入院时血磷值0.82 mmol/L，骨骼X线检查示长骨干骺端杯口状、毛刷样改变，诸骨改变符合佝偻病表现。患儿母亲存在身材矮小、双下肢畸形伴骨痛症状。基因检测发现患儿PHEX基因变异（c.1282C>T，p.Gln428*，来源于母亲）。予以布罗索尤单抗治疗后，患儿血磷值较用药前升高，碱性磷酸酶及甲状旁腺激素水平降低，生长速率较前增快，骨痛好转，活动耐量提高，骨骼畸形程度较前明显好转，且未发生药物相关不良反应。结论布罗索尤单抗用于治疗因PHEX基因变异导致XLH的患儿，可改善多项指标且安全性良好。

关键词: 布罗索尤单抗, X连锁低磷性佝偻病, PHEX基因, 低磷血症, 儿童

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

杨帆, 李娟, 张网林, 常国营, 李辛, 李芸芸, 佘佳笑, 林卡娜, 李浩, 王秀敏. 布罗索尤单抗治疗X连锁低磷性佝偻病临床分析[J]. 临床儿科杂志, 2025, 43(2): 105-111.

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.

图/表 5

图1

图2

图3

图4

表1

布罗索尤单抗治疗儿童低磷性佝偻病64周临床试验数据汇总"

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

表1

参考文献 20

[1]	Haffner D, Emma F, Eastwood DM, et al. Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia[J]. Nat Rev Nephrol, 2019, 15(7): 435-455. doi: 10.1038/s41581-019-0152-5 pmid: 31068690
[2]	Lambert AS, Linglart A. Hypocalcaemic and hypophosphatemic rickets[J]. Best Pract Res Clin Endocrinol Metab, 2018, 32(4): 455-476. doi: S1521-690X(18)30077-0 pmid: 30086869
[3]	中国妇幼保健协会儿童疾病和保健分会儿童遗传代谢疾病与保健学组, 北京医学会罕见病分会遗传代谢病学组, 中华预防医学会出生缺陷预防与控制专业委员会遗传病学组. X连锁显性遗传性低磷血症性佝偻病诊治专家共识[J]. 中国实用儿科杂志, 2022, 37(1): 1-6.
	China Maternal and Child Health Care Association, Children's Disease and Health Care Branch, Children's Genetic metabolic disease and Health care Group, Beijing Medical Association, Rare Disease Branch, Beijing Medical Association, Birth Defect Prevention and Control Professional Committee of genetic disease group. Expert consensus on diagnosis and treatment of X-linked dominant hereditary hypophosphatemic rickets[J]. Zhongguo Shiyong Erke Zazhi, 2022, 37(1) : 1-6
[4]	中华医学会儿科学分会内分泌遗传代谢学组, 中国罕见病联盟, 中华儿科杂志编辑委员会. 儿童X连锁低磷性佝偻病诊治与管理专家共识[J]. 中华儿科杂志, 2022, 60(6): 501-506.
	Endocrinology, Genetics and Metabolism Group, Chinese Society of Pediatrics, China Rare Disease Alliance, Editorial Board of Chinese Journal of Pediatrics. Expert consensus on diagnosis, treatment and management of X-linked hypophosphate rickets in children[J]. Zhonghua Erke Zazhi, 2022, 60(6): 501-506.
[5]	Yuan B, Takaiwa M, Clemens TL, et al. Aberrant Phex function in osteoblasts and osteocytes alone underlies murine X-linked hypophosphatemia[J]. J Clin Invest, 2008, 118(2): 722-734. doi: 10.1172/JCI32702 pmid: 18172553
[6]	Popowska E, Pronicka E, Sułek A, et al. X-linked hypophosphatemia in Polish patients. 1. Mutations in the PHEX gene[J]. J Appl Genet, 2000, 41(4): 293-302. pmid: 14564077
[7]	Whyte MP, Carpenter TO, Gottesman GS, et al. Efficacy and safety of burosumab in children aged 1-4 years with X-linked hypophosphataemia: a multicentre, open-label, phase 2 trial[J]. Lancet Diabetes Endocrinol, 2019, 7(3): 189-199.
[8]	Carpenter TO, Whyte MP, Imel EA, et al. Burosumab therapy in children with X-linked hypophosphatemia[J]. N Engl J Med, 2018, 378(21): 1987-1998.
[9]	Linglart A, Imel EA, Whyte MP, et al. Sustained efficacy and safety of burosumab, a monoclonal antibody to FGF23, in children with X-linked hypophosphatemia[J]. J Clin Endocrinol Metab, 2022, 107(3): 813-824.
[10]	Imel EA, Glorieux FH, Whyte MP, et al. Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial[J]. Lancet, 2019, 393(10189): 2416-2427. doi: S0140-6736(19)30654-3 pmid: 31104833
[11]	Namba N, Kubota T, Muroya K, et al. Safety and efficacy of burosumab in pediatric patients with X-linked hypophosphatemia: A phase 3/4 open-label trial[J]. J Endocr Soc, 2022, 6(5): bvac021.
[12]	Zhang C, Zhao Z, Sun Y, et al. Clinical and genetic analysis in a large Chinese cohort of patients with X-linked hypophosphatemia[J]. Bone, 2019, 121: 212-220. doi: S8756-3282(19)30030-4 pmid: 30682568
[13]	Baroncelli GI, Mora S. X-linked hypophosphatemic rickets: Multisystemic disorder in children requiring multidisciplinary management[J]. Front Endocrinol (Lausanne), 2021, 12: 688309.
[14]	López-Romero LC, Broseta JJ, Guillén Olmos E, et al. X-linked hypophosphatemic rickets: Diagnosis in adult and paucisymptomatic form[J]. Reumatologia clinica, 2021, 17(2): 116-117.
[15]	Haffner D, Emma F, Eastwood DM, et al. Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia[J]. Nat Rev Nephrol, 2019, 15(7): 435-455. doi: 10.1038/s41581-019-0152-5 pmid: 31068690
[16]	魏丽亚, 巩纯秀, 曹冰燕, 等. 儿童X连锁显性遗传性低磷血症性佝偻病临床及基因分析[J]. 中华儿科杂志, 2021, 59(8): 678-683.
	Wei LY, Gong CX, Cao BY, et al. Clinical and genetic analysis of X-linked dominant inherited hypophosphatemia rickets in children[J]. Zhonghua Erke Zazhi, 2021, 59(8): 678-683.
[17]	Bloudeau L, Linglart A, Flammier S, et al. X-linked hypophosphatemia, obesity and arterial hypertension: data from the XLH21 study[J]. Pediatr Nephrol, 2023, 38(3): 697-704.
[18]	Ward LM, Glorieux FH, Whyte MP, et al. Effect of burosumab compared with conventional therapy on younger vs older children with X-linked hypophosphatemia[J]. J Clin Endocrinol Metab, 2022, 107(8): e3241-e3253.
[19]	Walker EYX, Lindsay TAJ, Allgrove J, et al. Burosumab in management of X-linked hypophosphataemia: a retrospective cohort study of growth and serum phosphate levels[J]. Arch Dis Child. 2023 May;108(5):379-384.
[20]	Mughal MZ, Baroncelli GI, de Lucas‐Collantes C, et al. Burosumab for X‐linked hypophosphatemia in children and adolescents: opinion based on early experience in seven European countries[J]. Front Endocrinol (Lausanne), 2022, 13: 1034580.

布罗索尤单抗治疗X连锁低磷性佝偻病临床分析

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

RichHTML

PDF (PC)

赞

可视化

摘要/Abstract

引用本文

使用本文

图/表 5

参考文献 20

相关文章 15

Metrics

本文评价

推荐阅读 0

[1]	郝创利, 蒋吴君. COVID-19疫情对儿童呼吸道感染病原流行病学影响[J]. 临床儿科杂志, 2025, 43(3): 163-167.
[2]	徐雪娜, 李娇阳, 陈苏清, 张义祝, 蒋吴君, 郝创利. COVID-19大流行前、中、后苏州儿童RSV流行动态及其他病原混合阳性情况分析[J]. 临床儿科杂志, 2025, 43(3): 168-176.
[3]	李珊珊, 胡丹丹. 儿童甲型H1N1流行性感冒相关性脑病死亡危险因素分析[J]. 临床儿科杂志, 2025, 43(3): 177-183.
[4]	翟宇, 段素霞, 贾凡平, 贾永萍, 张京京, 郭映辉. 儿童呼吸道博卡病毒感染流行特征分析：一项单中心回顾性研究[J]. 临床儿科杂志, 2025, 43(3): 184-190.
[5]	赵培伟, 张蕾, 孟庆杰, 何学莲. 脑组织铁沉积神经变性病患儿的临床与遗传学分析[J]. 临床儿科杂志, 2025, 43(3): 199-203.
[6]	贾双珍, 孔琰, 刘前超, 朱艾琳, 吴捷. 儿童炎症性肠病的精准治疗研究与应用[J]. 临床儿科杂志, 2025, 43(3): 226-232.
[7]	李昭飞, 王凌超, 赵德安. 儿童食管腐蚀伤的临床诊治研究进展[J]. 临床儿科杂志, 2025, 43(3): 237-242.
[8]	乐慧娟, 吴瑾. 坏死性小肠结肠炎患儿外周血MDSCs数量变化及生物学特性分析：基于GEO数据库[J]. 临床儿科杂志, 2025, 43(2): 112-119.
[9]	黄柳芳, 吴博, 王莹. 儿童溃疡性结肠炎手术治疗的预测标志物分析[J]. 临床儿科杂志, 2025, 43(2): 120-127.
[10]	林丽华, 张宁, 陈奇洪, 陈莉莉, 陈丽羡, 杨运刚. 儿童支气管Dieulafoy病1例并文献复习[J]. 临床儿科杂志, 2025, 43(2): 135-140.
[11]	张硕, 赵雪珉, 沈秀华. 儿童青少年素食饮食行为对健康的影响[J]. 临床儿科杂志, 2025, 43(2): 157-162.
[12]	郭芳, 康磊, 武晓圆, 贾艳红, 邸亚楠, 贾莉, 徐梅先. 重症百日咳合并肺孢子菌肺炎患儿5例临床分析[J]. 临床儿科杂志, 2025, 43(2): 99-104.
[13]	罗明静, 余嘉明, 王晓东, 张小玲, 余阅, 张瑜, 文飞球, 刘四喜. 424例地中海贫血患儿异基因造血干细胞移植后继发侵袭性真菌病临床分析[J]. 临床儿科杂志, 2025, 43(1): 21-28.
[14]	刘冬霞, 金蓉, 林荣军. 儿童重症难治性肺炎支原体肺炎并发闭塞性支气管炎危险因素分析[J]. 临床儿科杂志, 2025, 43(1): 29-34.
[15]	钟瑾虹, 王灿, 陈芳. 婴幼儿纤维支气管镜诊疗中镇静技术的研究进展[J]. 临床儿科杂志, 2025, 43(1): 50-55.