Journal of Clinical Pediatrics ›› 2023, Vol. 41 ›› Issue (12): 946-954.doi: 10.12372/jcp.2023.23e0303
• Evidence-Based Medicine • Previous Articles Next Articles
HE Guanlan, WEI Qiufen(
), LI Na, CHEN Shaoping, LIU Yunyuan, LIAO Shasha, TANG Xiuneng(
)
Received:2023-04-11
Published:2023-12-15
Online:2023-12-04
HE Guanlan, WEI Qiufen, LI Na, CHEN Shaoping, LIU Yunyuan, LIAO Shasha, TANG Xiuneng. Meta-analysis of clinical efficacy of nusinersen in the treatment of children with spinal muscular atrophy[J].Journal of Clinical Pediatrics, 2023, 41(12): 946-954.
"
| 步骤 | 检索式 |
|---|---|
| #1 | "Muscular Atrophy, Spinal"[Mesh] |
| #2 | "Spinal Muscular atrophy"[Text Word] |
| #3 | SMA[Text Word] |
| #4 | #1 OR #2 OR #3 |
| #5 | "Oligonucleotides, Antisense"[Mesh] |
| #6 | nusinersen[Text Word] |
| #7 | spinraza[Text Word] |
| #8 | #5 OR #6 OR #7 |
| #9 | "treatment,outcome"[Mesh] |
| #10 | "treatment outcome*[Text Word]" |
| #11 | efficacy[Text Word] |
| #12 | #9 OR #10 OR #11 |
| #13 | #4 AND #8 AND #12 |
"
| 作 者 | 年份 | 患者例数 | 人群来源 | SMA分型 | 随访时间/月 | 结局指标 |
|---|---|---|---|---|---|---|
| Tscherter[ | 2022 | 11 | 瑞士 | 1 | >6 | ① |
| Pechmann[ | 2022 | 256 | 德国 | 2、3 | 14 | ②③ |
| Pane[ | 2022 | 73 | 意大利 | 2、3 | 24 | ②③ |
| Kotulska[ | 2022 | 298 | 波兰 | 1、2、3 | 12 | ①② |
| Pera[ | 2021 | 77 | 美国、英国、意大利 | 3 | >6 | ②③ |
| Pane[ | 2021 | 122 | 意大利 | 1 | 12 | ①④ |
| Modrzejewska[ | 2021 | 26 | 波兰 | 1 | 18-26 | ① |
| Mendonca[ | 2021 | 21 | 巴西 | 1 | >6 | ①④ |
| Konersman[ | 2021 | 19 | 美国 | 1、2、3 | 22 | ①② |
| Coratti[ | 2021 | 77 | 美国、英国、意大利 | 2 | 12 | ②③ |
| Szabo[ | 2020 | 57 | 匈牙利 | 1、2、3 | 10 | ①②③ |
| Audic[ | 2020 | 123 | 法国 | 1、2 | 12 | ①④ |
| Aragon-Gawinska[ | 2020 | 53 | 法国、比利时 | 1 | 14 | ①④ |
| Pechmann[ | 2018 | 61 | 德国 | 1 | >6 | ①④ |
"
| 作 者 | 年份 | 研究人群选择(0~4分) | 组间可比性(0~2分) | 结果测量(0~3分) | 总分 |
|---|---|---|---|---|---|
| Tscherter[ | 2022 | 3 | 2 | 3 | 8 |
| Pechmann[ | 2022 | 3 | 2 | 2 | 7 |
| Pane[ | 2022 | 3 | 2 | 3 | 8 |
| Kotulska[ | 2022 | 3 | 2 | 3 | 8 |
| Pera[ | 2021 | 3 | 2 | 3 | 8 |
| Pane[ | 2021 | 3 | 2 | 3 | 8 |
| Modrzejewska[ | 2021 | 3 | 2 | 3 | 8 |
| Mendonca[ | 2021 | 3 | 2 | 3 | 8 |
| Konersman[ | 2021 | 3 | 2 | 3 | 8 |
| Coratti[ | 2021 | 3 | 2 | 3 | 8 |
| Szabo[ | 2020 | 3 | 2 | 3 | 8 |
| Audic[ | 2020 | 3 | 2 | 3 | 8 |
| Aragon-Gawinska[ | 2020 | 3 | 2 | 3 | 8 |
| Pechmann[ | 2018 | 3 | 2 | 3 | 8 |
| 总分 | 42/56 | 28/28 | 41/42 |
"
| 结局指标 | 作 者 | 年份 | 事件数(X) | 总例数(N) | N×P1 | N×(1-P1) |
|---|---|---|---|---|---|---|
| CHOP INTEND 临床改善率 | Tscherter[ | 2022 | 10 | 11 | 10 | 1 |
| Kotulska[ | 2022 | 129 | 170 | 129 | 41 | |
| Pechmann[ | 2018 | 47 | 61 | 47 | 14 | |
| HINE-2 临床改善率 | Mendonca[ | 2021 | 6 | 21 | 6 | 15 |
| Konersman[ | 2021 | 1 | 5 | 1 | 4 | |
| Aragon-Gawinska[ | 2020 | 24 | 44 | 24 | 20 | |
| Pechmann[ | 2018 | 19 | 61 | 19 | 42 | |
| HINE-2临床改善率(亚组分析) | Mendonca[ | 2021 | 6 | 21 | 6 | 15 |
| Konersman[ | 2021 | 1 | 5 | 1 | 4 | |
| Pechmann[ | 2018 | 19 | 61 | 19 | 42 | |
| HFMSE临床改善率 | Kotulska[ | 2022 | 88 | 121 | 81 | 33 |
| Pechmann[ | 2022 | 63 | 147 | 63 | 84 | |
| Konersman[ | 2021 | 6 | 9 | 6 | 3 | |
| Coratti[ | 2021 | 26 | 77 | 26 | 51 | |
| RULM 临床改善率 | Pechmann[ | 2022 | 83 | 124 | 83 | 41 |
| Konersman[ | 2021 | 5 | 8 | 5 | 3 | |
| Coratti[ | 2021 | 27 | 73 | 27 | 46 | |
| RULM 临床改善率(亚组分析) | Pechmann[ | 2022 | 83 | 124 | 83 | 41 |
| Konersman[ | 2021 | 5 | 8 | 5 | 3 |
"
| 结局指标 | 纳入 研究数 | 质量升级因素 | 结果汇总 | ||||
|---|---|---|---|---|---|---|---|
| 效应值 是否很大 | 存在剂量- 效应关系 | 存在降低疗效 的混杂因素 | 研究对象 /例 | MD/改善率 (95%CI) | 证据质量 | ||
| CHOP INTEND评分 | 8 | 效应值较大 | 否 | 否 | 369 | 9.08(7.17~10.99) | 中 |
| CHOP INTEND临床改善率 | 3 | 效应值较大 | 否 | 否 | 242 | 0.77(0.71~0.82) | 中 |
| HINE-2评分 | 6 | 否 | 否 | 否 | 219 | 2.08(1.26~2.90) | 低 |
| HINE-2临床改善率 | 4 | 否 | 否 | 否 | 131 | 0.39(0.31~0.48) | 低 |
| HFMSE评分 | 7 | 否 | 否 | 否 | 508 | 3.83(2.15~5.50) | 低 |
| HFMSE临床改善率 | 4 | 否 | 否 | 否 | 354 | 0.53(0.33~0.72) | 低 |
| RULM评分 | 6 | 否 | 否 | 否 | 306 | 2.42(1.33~3.52) | 低 |
| RULM临床改善率 | 3 | 否 | 否 | 否 | 205 | 0.56(0.49~0.63) | 低 |
| [1] |
Lunn MR, Wang CH. Spinal muscular atrophy[J]. The Lancet, 2008, 371: 2120-2133.
doi: 10.1016/S0140-6736(08)60921-6 |
| [2] |
Schorling DC, Pechmann A, Kirschner J. Advances in treatment of spinal muscular atrophy-new phenotypes, new challenges, new implications for care[J]. J Neuromuscul Dis, 2020, 7: 1-13.
doi: 10.3233/JND-190424 pmid: 31707373 |
| [3] |
Ramdas S, Servais L. New treatments in spinal muscular atrophy: an overview of currently available data[J]. Expert Opin Pharmacother, 2020, 21: 307-315.
doi: 10.1080/14656566.2019.1704732 pmid: 31973611 |
| [4] | 陈瑜毅, 韩蕴丽, 李杏, 等. 31例儿童脊髓性肌萎缩症临床与基因分析[J]. 临床儿科杂志, 2021, 39(10): 745-749. |
| [5] | Finkel RS, Chiriboga CA, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study[J]. Lancet, 2016, 17, 388 (10063): 3017-3026. |
| [6] |
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.
doi: 10.1056/NEJMoa1702752 |
| [7] | 脊髓性肌萎缩症临床实践指南工作组. 脊髓性肌萎缩症临床实践指南[J]. 中国循证儿科杂志, 2023, 18(1): 1-12. |
| [8] |
Mazzone ES, Mayhew A, Montes J, et al. Revised upper limb module for spinal muscular atrophy: development of a new module[J]. Muscle Nerve, 2017, 55: 869-874.
doi: 10.1002/mus.25430 pmid: 27701745 |
| [9] | 曾宪涛, 刘慧, 陈曦, 等. Meta分析系列之四: 观察性研究的质量评价工具[J]. 中国循证心血管医学杂志, 2012, 4(4): 297-299. |
| [10] | Wells G, Shea B, O'Connell D, et al. NewCastle-Ottawa Quality Assessment Scale--Cohort Studies[EB/OL]. [2012-06-15]. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. |
| [11] |
Yao H, Chen X, Tan X. Efficacy and safety of apatinib in the treatment of osteosarcoma: a single-arm meta-analysis among Chinese patients[J]. BMC Cancer, 2021, 21(1): 449.
doi: 10.1186/s12885-021-08154-3 pmid: 33892656 |
| [12] | 陈月红, 杜亮, 耿兴远, 等. 无对照二分类数据的meta分析在RevMan软件中的实现[J]. 中国循证医学杂志, 2014, 14(7): 889-896. |
| [13] |
Tscherter A, Rüsch CT, Baumann D, et al. Evaluation of real-life outcome data of patients with spinal muscular atrophy treated with nusinersen in Switzerland[J]. Neuromuscul Disord, 2022, 32(5): 399-409.
doi: 10.1016/j.nmd.2022.02.001 |
| [14] | Pechmann A, Behrens M, Dörnbrack K, et al. Improved upper limb function in non-ambulant children with SMA type 2 and 3 during nusinersen treatment: a prospective 3-years SMArtCARE registry study[J]. Orphanet J Rare Dis, 2022, 23, 17(1): 384. |
| [15] |
Pane M, Coratti G, Pera MC, et al. Nusinersen efficacy data for 24-month in type 2 and 3 spinal muscular atrophy[J]. Ann Clin Transl Neurol, 2022, 9(3): 404-409.
doi: 10.1002/acn3.v9.3 |
| [16] |
Kotulska K, Chmielewski D, Mazurkiewicz-Bełdzińska M, et al. Safety, tolerability, and efficacy of a widely available nusinersen program for polish children with spinal muscular atrophy[J]. Eur J Paediatr Neurol, 2022, 39: 103-109.
doi: 10.1016/j.ejpn.2022.06.001 |
| [17] |
Pera MC, Coratti G, Bovis F, et al. Nusinersen in pediatric and adult patients with type III spinal muscular atrophy[J]. Ann Clin Transl Neurol, 2021, 8(8): 1622-1634.
doi: 10.1002/acn3.v8.8 |
| [18] |
Pane M, Coratti G, Sansone VA, et al. Type I SMA "new natural history": long-term data in nusinersen-treated patients[J]. Ann Clin Transl Neurol, 2021, 8(3): 548-557.
doi: 10.1002/acn3.v8.3 |
| [19] |
Modrzejewska S, Kotulska K, Kopyta I, et al. Nusinersen treatment of spinal muscular atrophy type 1 - results of expanded access programme in Poland[J]. Neurol Neurochir Pol, 2021, 55(3): 289-294.
doi: 10.5603/PJNNS.a2021.0020 pmid: 33565602 |
| [20] |
de Holanda Mendonça R, Jorge Polido G, Ciro M, et al. Clinical outcomes in patients with spinal muscular atrophy type 1 treated with nusinersen[J]. J Neuromuscul Dis, 2021, 8(2): 217-224.
doi: 10.3233/JND-200533 pmid: 33459657 |
| [21] |
Konersman CG, Ewing E, Yaszay B, et al. Nusinersen treatment of older children and adults with spinal muscular atrophy[J]. Neuromuscul Disord, 2021, 31(3): 183-193.
doi: 10.1016/j.nmd.2020.12.006 |
| [22] |
Coratti G, Pane M, Lucibello S, et al. Age related treatment effect in type II spinal muscular atrophy pediatric patients treated with nusinersen[J]. Neuromuscul Disord, 2021, 31(7): 596-602.
doi: 10.1016/j.nmd.2021.03.012 |
| [23] |
Szabó L, Gergely A, Jakus R, et al. Efficacy of nusinersen in type 1, 2 and 3 spinal muscular atrophy: Real world data from Hungarian patients[J]. Eur J Paediatr Neurol, 2020, 27: 37-42.
doi: 10.1016/j.ejpn.2020.05.002 |
| [24] |
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.
doi: 10.1186/s13023-020-01414-8 pmid: 32532349 |
| [25] |
Aragon-Gawinska K, Daron A, Ulinici A, Vet al. Sitting in patients with spinal muscular atrophy type 1 treated with nusinersen[J]. Dev Med Child Neurol, 2020, 62(3): 310-314.
doi: 10.1111/dmcn.14412 pmid: 31799720 |
| [26] |
Pechmann A, Langer T, Schorling D, et al. Evaluation of children with SMA type 1 under treatment with nusinersen within the expanded access program in Germany[J]. J Neuromuscul Dis, 2018, 5(2): 135-143.
doi: 10.3233/JND-180315 pmid: 29689734 |
| [27] | 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. |
| [28] | 陈峥, Yoram Nevo, Tanya Moss. 诺西那生钠治疗脊髓性肌萎缩[J]. 中国临床研究, 2019, 32(6): 721-725. |
| [29] |
Nance JR. Spinal muscular atrophy[J]. Continuum (Minneap Minn), 2020, 26: 1348-1368.
doi: 10.1212/CON.0000000000000918 pmid: 33003005 |
| [30] |
Faravelli I, Nizzardo M, Comi GP, et al. Spinal muscular atrophy--recent therapeutic advances for an old challenge[J]. Nat Rev Neurol, 2015, 11: 351-359.
doi: 10.1038/nrneurol.2015.77 pmid: 25986506 |
| [31] |
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.
doi: 10.1212/WNL.0000000000007527 |
| [32] |
Haataja L, Mercuri E, Regev R, et al. Optimality score for the neurologic examination of the infant at 12 and 18 months of age[J]. J Pediatr, 1999, 135: 153-161.
doi: 10.1016/S0022-3476(99)70016-8 |
| [33] |
Al-Zaidy SA, Kolb SJ, Lowes L, et al. AVXS-101 (Onasemnogene Abeparvovec) for SMA1: comparative study with a prospective natural history cohort[J]. J Neuromuscul Dis, 2019, 6(3): 307-317.
doi: 10.3233/JND-190403 pmid: 31381526 |
| [34] |
De Sanctis R, Pane M, Coratti G, et al. Clinical phenotypes and trajectories of disease progression in type 1 spinal muscular atrophy[J]. Neuromuscul Disord, 2018, 28(1): 24-28.
doi: 10.1016/j.nmd.2017.09.015 |
| [35] | 胡超平, 李文辉, 朱小妹, 等. 脊髓性肌萎缩症自然病史的系统评价/meta分析[J]. 中国循证儿科杂志, 2022, 17(6): 420-425. |
| [36] |
Chabanon A, Seferian AM, Daron A, et al. Prospective and longitudinal natural history study of patients with type 2 and 3 spinal muscular atrophy: baseline data NatHisSMA study[J]. PLoS One, 2018, 13(7): e0201004.
doi: 10.1371/journal.pone.0201004 |
| [37] |
Coratti G, Messina S, Lucibello S, et al. Clinical variability in spinal muscular atrophy type III[J]. Ann Neurol, 2020, 88(6): 1109-1117.
doi: 10.1002/ana.v88.6 |
| [38] |
Coratti G, Pera MC, Montes J, et al. Different trajectories in upper limb and gross motor function in spinal muscular atrophy[J]. Muscle Nerve, 2021, 64(5): 552-559.
doi: 10.1002/mus.27384 pmid: 34327716 |
| [39] |
Gavriilaki M, Moschou M, Papaliagkas V, et al. Nusinersen in adults with 5q spinal muscular atrophy: a systematic review and meta-analysis[J]. Neurotherapeutics, 2022, 19(2): 464-475.
doi: 10.1007/s13311-022-01200-3 pmid: 35178673 |
| [40] | Wijngaarde CA, Stam M, Otto LAM, et al. Muscle strength and motor function in adolescents and adults with spinal muscular atrophy[J]. Neurology, 2020, 95(14): e1988-e1998. |
| [1] | LIN Jinfeng, CHEN Yi, DENG Yan, FENG Ai, HUANG Juan, CHEN Lizhu, XIE Jingqi, NIE Xiaojing. A comparative study on the detection of anti-Nephrin antibodies in children's nephrotic syndrome by chemiluminescence method and cell-based assay [J]. Journal of Clinical Pediatrics, 2026, 44(8): 682-689. |
| [2] | ZHENG Fangyuan, WANG Miao, DING Mingming, LU Aidong, JIA Yueping, ZENG Huimin, ZHANG Leping. Next-generation sequencing identified gene variants and their prognostic impact in pediatric Philadelphia chromosome positive acute lymphoblastic leukemia [J]. Journal of Clinical Pediatrics, 2026, 44(8): 690-697. |
| [3] | ZHANG Xiao, FANG Hongjun, KUANG Xiaojun, WANG Lijuan, WU Zhao, JIANG Sha, LI Pei, WU Liwen. Analysis of the clinical and electrophysiological characteristics of atonic seizures in children [J]. Journal of Clinical Pediatrics, 2026, 44(8): 698-704. |
| [4] | WANG Mengqian, YANG Hui. Case series analysis of 13 intestinal Behcet’s syndrome in children [J]. Journal of Clinical Pediatrics, 2026, 44(8): 705-711. |
| [5] | WU Xirong, GAO Qi, GUO Siyuan, YIN Qingqin, QIN Qiang, YIN Ju, JIAO Anxia, CHEN Chenghao, WU Di, WANG Bei, DUAN Xiaomin, PENG Yun, XU Baoping, GAO Liwei. Clinical characteristics and prognosis of pulmonary mucormycosis in children with diabetes mellitus [J]. Journal of Clinical Pediatrics, 2026, 44(8): 712-720. |
| [6] | HAN Yanan, GE Lanlan, CUI Jieyuan. A case report of branchio-oto-renal syndrome caused by EYA1 gene variant with a 6-year follow-up [J]. Journal of Clinical Pediatrics, 2026, 44(8): 721-726. |
| [7] | SHI Jiayi, GAO Chunlin, JIA Lili, LU Yunyun, SUN Tao, ZHU Xiaodong, XIA Zhengkun, ZHANG Pei. Phenotypic characteristics and prognostic analysis of a pedigree with childhood isolated nephrotic syndrome caused by compound heterozygous mutations in the COQ2 gene [J]. Journal of Clinical Pediatrics, 2026, 44(8): 727-732. |
| [8] | Rachel Rosen, Osvaldo Borrelli, Christophe Faure, Katja Karrento, Usha Krishnan, Samuel Nurko, Nathalie Rommel, Alan Silverman, Michiel van Wijk, Marc Benninga (Author), Chinese Medical Association Parenteral and Enteral Nutrition Branch Pediatrics Group, The Subspecialty Group of Gastroenterology, The Society of Pediatric, Chinese Medical Association, Gastroenterology Group, Pediatrician Branch, Chinese Medical Doctor Association (Translator). Core interpretation and explanation of Rome Ⅴ diagnostic criteria: upper gastrointestinal disorders of gut-brain interaction in children and adolescents [J]. Journal of Clinical Pediatrics, 2026, 44(7): 595-608. |
| [9] | Carlo Di Lorenzo, Miguel Saps, Bruno P. Chumpitazi, Shaman Rajindrajith, Annamaria Staiano, Nikhil Thapar, Miranda van Tilburg, Carlos Velasco-Benítez, Arine Vlieger (Author), Chinese Medical Association Parenteral and Enteral Nutrition Branch Pediatrics Group, The Subspecialty Group of Gastroenterology, The Society of Pediatric, Chinese Medical Association, Gastroenterology Group, Pediatrician Branch, Chinese Medical Doctor Association (Translator). Core interpretation and explanation of Rome Ⅴ diagnostic criteria: lower and biliary disorders of gut-brain interaction in children and adolescents [J]. Journal of Clinical Pediatrics, 2026, 44(7): 609-621. |
| [10] | LI Xufeng, TANG Haoxun, LI Xingjun, ZHANG Lize, GAO Chenqing, ZHAO Shunying, LIU Jianhua. Clinical characteristics, chest CT imaging phenotypes, and their correlation with prognosis in 76 children with Chlamydia pneumoniae pneumonia [J]. Journal of Clinical Pediatrics, 2026, 44(7): 622-627. |
| [11] | WANG Zhen, SHAO Jingbo, ZHANG Na, XIA Min, ZHU Jiashi, DU Chengkan, LI Hong. Factors influencing long-term recurrence in pediatric acute lymphoblastic leukemia patients with low-risk disease at initial diagnosis: a five-year follow-up analysis of 254 cases from a single center [J]. Journal of Clinical Pediatrics, 2026, 44(7): 628-635. |
| [12] | GUO Xuemei, XUE Yao, WANG Yongren, RONG Liucheng, FANG Yongjun, LIN Rufeng. Clinical features and prognosis of childhood acute myeloid leukemia with CBFA2T3::GLIS2 fusion [J]. Journal of Clinical Pediatrics, 2026, 44(7): 636-643. |
| [13] | YANG Lijun, FU Dongxia, CUI Yan, YANG Junmei, ZHANG Liming. Clinical manifestation and genetic analysis of CHARGE syndrome caused by CHD7 gene variation [J]. Journal of Clinical Pediatrics, 2026, 44(7): 644-650. |
| [14] | HU Yan, YANG Fan, LIANG Aimin, MAO Meng. Identification and management of faltering growth in children: insights from the 13th International Conference on Nutrition and Growth [J]. Journal of Clinical Pediatrics, 2026, 44(6): 485-488. |
| [15] | LIU Ziyao, WANG Congying, WANG Hongmao, ZHANG Mingming, XU Yingjie, LAI Jianming, NIU Wenquan, LI Xiaohui. Early differentiation of Kawasaki disease with joint symptoms and systemic juvenile idiopathic arthritis with Kawasaki disease-like symptoms: a single-center retrospective study [J]. Journal of Clinical Pediatrics, 2026, 44(6): 489-498. |
|
||