诺西那生钠治疗脊髓性肌萎缩症儿童的临床分析

doi:10.7499/j.issn.1008-8830.2401082

摘要
图/表
参考文献(31)
相关文章 (15)
点击分布统计
下载分布统计

全文: PDF (655 KB) [HTML]
输出: BibTeX | EndNote (RIS) 背景资料

摘要目的探讨诺西那生钠治疗脊髓性肌萎缩症（spinal muscular atrophy, SMA）患儿的疗效及安全性。方法回顾性分析2022年2月—2024年2月于山西省儿童医院接受诺西那生钠治疗及多学科协作诊疗管理随访的50例5q SMA患儿的临床资料。结果与基线相比，分别有67%（8/12）、74%（35/47）、74%（35/47）的SMA患儿费城儿童医院婴儿神经肌肉疾病测试、Hammersmith功能性运动量表扩展版（Hammersmith Functional Motor Scale Expanded）、上肢模块修订版（Revised Upper Limb Module）评分结果有临床意义的改善；6 min步行试验的距离从207.00（179.00，281.50）m增至233.00（205.25，287.50）m（P<0.05）。24例（48%）SMA患儿给予诺西那生钠后耐受良好，2 034个实验室结果中无显著、持续性异常，未观察到严重或相关免疫学不良事件发生。27例存在限制性通气功能障碍者的用力肺活量占预测值百分比及15例维生素D缺乏者的25-(OH)D水平治疗前后比较差异有统计学意义（P<0.05）。结论 SMA患儿经诺西那生钠治疗后，运动功能量表应答比例持续提升，且耐受性及安全性良好。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	郭瑾
	武运红
	张临霞
	纪惠茹
	周娜
	胡晓月

关键词 ：脊髓性肌萎缩症, 诺西那生钠, 疗效, 安全性, 儿童

Abstract：Objective To investigate the efficacy and safety of nusinersen sodium in the treatment of children with spinal muscular atrophy (SMA). Methods A retrospective analysis was conducted on the clinical data of 50 children with 5q SMA who received nusinersen sodium treatment and multidisciplinary treatment management in Shanxi Children's Hospital from February 2022 to February 2024. Results Compared with the baseline data, 67% (8/12), 74% (35/47), and 74% (35/47) of the SMA children had a clinically significant improvement in the scores of Philadelphia Infant Test of Neuromuscular Disorders, Hammersmith Functional Motor Scale Expanded, and Revised Upper Limb Module, respectively, and the distance of 6-minute walking test increased from 207.00 (179.00, 281.50) meters to 233.00 (205.25, 287.50) meters (P<0.05) after nusinersen sodium treatment. Of all 50 children with SMA, 24 (48%) showed good tolerability after administration, with no significant or persistent abnormalities observed in 2 034 laboratory test results, and furthermore, there were no serious or immunological adverse events related to the treatment. After treatment, there was a significant change in forced vital capacity as a percentage of the predicted value in 27 children with restrictive ventilatory dysfunction, as well as a significant change in the level of 25-(OH) vitamin D in 15 children with vitamin D deficiency (P<0.05). Conclusions For children with SMA, treatment with nusinersen sodium can continuously improve the response rates of motor function scales, with good tolerability and safety.

Key words： Spinal muscular atrophy Nusinersen sodium Efficacy Safety Child

收稿日期: 2024-01-16

通讯作者: 武运红，女，主任医师。Email： wuyunhong510@163.com。 E-mail: wuyunhong510@163.com

作者简介: 郭瑾，女，硕士研究生；

引用本文:

郭瑾,武运红,张临霞等. 诺西那生钠治疗脊髓性肌萎缩症儿童的临床分析[J]. 中国当代儿科杂志, 2024, 26(7): 743-749.

GUO Jin,WU Yun-Hong,ZHANG Lin-Xia et al. Clinical efficacy of nusinersen sodium in the treatment of children with spinal muscular atrophy[J]. CJCP, 2024, 26(7): 743-749.

链接本文:

http://www.zgddek.com/CN/10.7499/j.issn.1008-8830.2401082 或 http://www.zgddek.com/CN/Y2024/V26/I7/743

	Lefebvre S, Bürglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy-determining gene[J]. Cell, 1995, 80(1): 155-165. PMID: 7813012. DOI: 10.1016/0092-8674(95)90460-3.
	2 北京医学会罕见病分会, 北京医学会医学遗传学分会, 北京医学会神经病学分会神经肌肉病学组, 等. 脊髓性肌萎缩症多学科管理专家共识[J]. 中华医学杂志, 2019, 99(19): 1460-1467. DOI: 10.3760/cma.j.issn.0376-2491.2019.19.006.
	Arkblad E, Tulinius M, Kroksmark AK, et al. A population-based study of genotypic and phenotypic variability in children with spinal muscular atrophy[J]. Acta Paediatr, 2009, 98(5): 865-872. PMID: 19154529. DOI: 10.1111/j.1651-2227.2008.01201.x.
	Su YN, Hung CC, Lin SY, et al. Carrier screening for spinal muscular atrophy (SMA) in 107,611 pregnant women during the period 2005-2009: a prospective population-based cohort study[J]. PLoS One, 2011, 6(2): e17067. PMID: 21364876. PMCID: PMC3045421. DOI: 10.1371/journal.pone.0017067.
	5 中国医师协会儿科医师分会, 中国医师协会儿科医师分会儿童呼吸学组. 脊髓性肌萎缩症呼吸管理专家共识（2022版）[J]. 中华实用儿科临床杂志, 2022, 37(6): 401-411. DOI: 10.3760/cma.j.cn101070-20220124-00092.
	Glanzman AM, Mazzone E, Main M, et al. The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND): test development and reliability[J]. Neuromuscul Disord, 2010, 20(3): 155-161. PMID: 20074952. PMCID: PMC3260046. DOI: 10.1016/j.nmd.2009.11.014.
	O'Hagen JM, Glanzman AM, McDermott MP, et al. An expanded version of the Hammersmith Functional Motor Scale for SMA II and III patients[J]. Neuromuscul Disord, 2007, 17(9-10): 693-697. PMID: 17658255. DOI: 10.1016/j.nmd.2007.05.009.
	Pera MC, Coratti G, Mazzone ES, et al. Revised Upper Limb Module for spinal muscular atrophy: 12 month changes[J]. Muscle Nerve, 2019, 59(4): 426-430. PMID: 30677148. DOI: 10.1002/mus.26419.
	Dunaway Young S, Montes J, Kramer SS, et al. Six-Minute Walk Test is reliable and valid in spinal muscular atrophy[J]. Muscle Nerve, 2016, 54(5): 836-842. PMID: 27015431. DOI: 10.1002/mus.25120.
	Finkel RS, Mercuri E, Darras BT, et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy[J]. N Engl J Med, 2017, 377(18): 1723-1732. PMID: 29091570. DOI: 10.1056/NEJMoa1702752.
	Darras BT, Chiriboga CA, Iannaccone ST, et al. Nusinersen in later-onset spinal muscular atrophy: long-term results from the phase 1/2 studies[J]. Neurology, 2019, 92(21): e2492-e2506. PMID: 31019106. PMCID: PMC6541434. DOI: 10.1212/WNL.0000000000007527.
	12 孟坤, 夏姗姗, 丁亚平, 等. 《儿科重症监护输血和贫血专家倡议——控制/防止出血: 危重儿童血浆和血小板输注实践的建议和专家共识》解读[J]. 中国实用儿科杂志, 2022, 37(9): 650-655. DOI: 10.19538/j.ek2022090602.
	Goedeker NL, Gibbons JL, Varadhachary AS, et al. Laboratory monitoring of nusinersen safety[J]. Muscle Nerve, 2021, 63(6): 902-905. PMID: 33675054. DOI: 10.1002/mus.27217.
	Green RM, Flamm S. Aga technical review on the evaluation of liver chemistry tests[J]. Gastroenterology, 2002, 123(4): 1367-1384. PMID: 12360498. DOI: 10.1053/gast.2002.36061.
	15 周继群. 尿ACR和微量白蛋白对肾早期损伤诊断与治疗的价值[J]. 现代诊断与治疗, 2022, 33(19): 2960-2962.
	16 李海冰, 夏雨, 叶文松, 等. 脊髓性肌萎缩症髋关节和脊柱畸形的初步研究[J]. 中华小儿外科杂志, 2020, 41(10): 926-932. DOI: 10.3760/cma.j.cn421158-20200217-00081.
	17 杨银升, 武运红, 韩虹, 等. 左乙拉西坦奥卡西平对43例儿童癫痫骨代谢影响的临床研究[J]. 中国药物与临床, 2020, 20(17): 2865-2866. DOI: 10.11655/zgywylc2020.17.015.
	毛姗姗, 冯艺杰, 徐璐, 等. 诺西那生钠修正治疗儿童脊髓性肌萎缩症随访分析[J]. 中华儿科杂志, 2022, 60(7): 688-693. PMID: 35768357. DOI: 10.3760/cma.j.cn112140-20211223-01075.
	Matsumoto H, Clayton-Krasinski DA, Klinge SA, et al. Development and initial validation of the Assessment of Caregiver Experience with Neuromuscular Disease[J]. J Pediatr Orthop, 2011, 31(3): 284-292. PMID: 21415688. DOI: 10.1097/BPO.0b013e31820fc522.
	Mercuri E, Darras BT, Chiriboga CA, et al. Nusinersen versus sham control in later-onset spinal muscular atrophy[J]. N Engl J Med, 2018, 378(7): 625-635. PMID: 29443664. DOI: 10.1056/NEJMoa1710504.
	Chiriboga CA, Swoboda KJ, Darras BT, et al. Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy[J]. Neurology, 2016, 86(10): 890-897. PMID: 26865511. PMCID: PMC4782111. DOI: 10.1212/WNL.0000000000002445.
	Audic F, de la Banda MGG, Bernoux D, et al. Effects of nusinersen after one year of treatment in 123 children with SMA type 1 or 2: a French real-life observational study[J]. Orphanet J Rare Dis, 2020, 15(1): 148. PMID: 32532349. PMCID: PMC7291731. DOI: 10.1186/s13023-020-01414-8.
	Kolb SJ, Coffey CS, Yankey JW, et al. Natural history of infantile-onset spinal muscular atrophy[J]. Ann Neurol, 2017, 82(6): 883-891. PMID: 29149772. PMCID: PMC5776712. DOI: 10.1002/ana.25101.
	usakowska A, Wójcik A, Fr?czek A, et al. Long-term nusinersen treatment across a wide spectrum of spinal muscular atrophy severity: a real-world experience[J]. Orphanet J Rare Dis, 2023, 18(1): 230. PMID: 37542300. PMCID: PMC10401775. DOI: 10.1186/s13023-023-02769-4.
	Darras BT, Farrar MA, Mercuri E, et al. An integrated safety analysis of infants and children with symptomatic spinal muscular atrophy (SMA) treated with nusinersen in seven clinical trials[J]. CNS Drugs, 2019, 33(9): 919-932. PMID: 31420846. PMCID: PMC6776494. DOI: 10.1007/s40263-019-00656-w.
	Mercuri E, Finkel RS, Muntoni F, et al. Diagnosis and management of spinal muscular atrophy: part 1: recommendations for diagnosis, rehabilitation, orthopedic and nutritional care[J]. Neuromuscul Disord, 2018, 28(2): 103-115. PMID: 29290580. DOI: 10.1016/j.nmd.2017.11.005.
	Zhou Y, Chen J, Gong X, et al. Nutrition status survey of type 2 and 3 spinal muscular atrophy in Chinese population[J]. Nutr Neurosci, 2022, 25(7): 1488-1494. PMID: 33487140. DOI: 10.1080/1028415X.2020.1871212.
	28 彭晓音. 脊髓性肌萎缩症患儿骨密度状况及其影响因素分析[D]. 北京: 北京协和医学院, 2022.
	Wijngaarde CA, Veldhoen ES, van Eijk RPA, et al. Natural history of lung function in spinal muscular atrophy[J]. Orphanet J Rare Dis, 2020, 15(1): 88. PMID: 32276635. PMCID: PMC7149916. DOI: 10.1186/s13023-020-01367-y.
	Cunha MC, Oliveira AS, Labronici RH, et al. Spinal muscular atrophy type II (intermediary) and III (Kugelberg-Welander). Evolution of 50 patients with physiotherapy and hydrotherapy in a swimming pool[J]. Arq Neuropsiquiatr, 1996, 54(3): 402-406. PMID: 9109983. DOI: 10.1590/s0004-282x1996000300007.
	De Vivo D, Bertini E, Swoboda K, et al. Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study[J]. Neuromuscular Disorders, 2019, 29(11). PMID: 31704158; PMCID:PMC7127286. DOI: 10.1016/j.nmd.2019.09.007.