Nusinersen与基因疗法治疗1型脊髓性肌萎缩症的临床效果比较。

IF 9.7 1区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Juliette Ropars, Claude Cances, Rocio Garcia-Uzquiano, Marta Gomez-Garcia de la Banda, Christine Barnerias, Frédérique Audic, Julien Durigneux, Cécile Halbert, Lionelle Nkam, Vincent Laugel, Caroline Espil, Ulrike Walther-Louvier, Jean-Baptiste Davion, Arnaud Isapof, Laure Le Goff, Isabelle Desguerre, Susana Quijano-Roy, Lamiae Grimaldi
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引用次数: 0

摘要

重要性:治疗的进步已经改变了脊髓性肌萎缩症(SMA)的预后。鉴于这些创新疗法的终身影响,迫切需要有关其疗效的比较数据。目的:比较nusinersen与onasemnogene abparvovec基因治疗一线治疗儿童1型SMA (SMA1)的临床效果。设计、环境和参与者:这项比较有效性研究使用了2016年9月至2024年7月法国国家SMA登记处的数据。随访期从开始治疗开始,一直持续到2024年7月22日或死亡。基因确诊的SMA1 (a、b或c型)患儿在诊断后6个月内接受诺森森或基因治疗作为一线治疗,并随访至少24个月。匹配标准包括年龄、费城儿童医院婴儿神经肌肉疾病测试的基线评分、治疗开始时的呼吸和营养状况。暴露:一线治疗,诺森森或基因治疗。主要结局和测量指标:结局包括呼吸和营养支持需求、运动功能和不满意的临床反应(UCR)——由于反应不足导致的死亡、治疗切换(或基因治疗增加)、开始喂养支持和/或无法独立坐着。结果:在登记的1366例患者中,309例被诊断为SMA1。12对配对的24名儿童符合纳入标准(14名[58%]男性;治疗开始时的平均[SD]年龄,6.1[3.0]个月[范围,2.3-11.9个月])。3例患者(1例接受基因治疗[8%],2例接受nusinersen[17%])在治疗一年内死亡。治疗后2年,接受基因治疗的11例存活患者中有1例(9%)需要营养支持,而接受nusinersen治疗的10例患者中有5例(50%)需要营养支持,接受基因治疗的11例患者中有5例(45%)需要夜间通气,而接受nusinersen治疗的10例患者中有8例(80%)需要夜间通气。运动结果组间具有可比性(chop - intent评分演变的配对内平均[SE]差异为-1.69[1.24]分;P = 0.17)。12例接受nusinersen治疗的患者中有8例(67%)发生UCR, 12例接受基因治疗的患者中有3例(25%)发生UCR。结论和相关性:在这项针对SMA1患儿的比较疗效研究中,与对照组相比,基因治疗与更低的UCR发生率和更少的支持性护理需求相关。这些探索性发现值得在更大规模的研究中得到证实。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comparative Clinical Outcomes of Nusinersen and Gene Therapy in Spinal Muscular Atrophy Type 1.

Importance: Therapeutic advances have transformed the prognosis of spinal muscular atrophy (SMA). Given the lifelong implications of these innovative therapies, comparative data on their efficacy are urgently required.

Objective: To compare clinical outcomes of nusinersen and onasemnogene abeparvovec gene therapy as first-line treatments in children with SMA type 1 (SMA1).

Design, setting, and participants: This comparative effectiveness study used data from the French National SMA Registry from September 2016 to July 2024. The follow-up period started at treatment initiation and continued until July 22, 2024, or death. Children with genetically confirmed SMA1 (types a, b, or c) treated within 6 months of diagnosis with either nusinersen or gene therapy as first-line therapy and followed up for at least 24 months were included. Matching criteria included age, baseline score on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders, and respiratory and nutritional status at treatment initiation.

Exposure: First-line treatment with either nusinersen or gene therapy.

Main outcomes and measures: Outcomes included respiratory and nutritional support needs, motor function, and unsatisfactory clinical response (UCR)- a composite of death, treatment switch (or, for gene therapy, addition) due to inadequate response, initiation of feeding support, and/or failure to achieve independent sitting.

Results: Among 1366 patients enrolled in the registry, 309 were diagnosed with SMA1. Twenty-four children in 12 matched pairs met inclusion criteria (14 [58%] male; mean [SD] age at treatment initiation, 6.1 [3.0] months [range, 2.3-11.9 months]). Three patients (1 receiving gene therapy [8%], 2 receiving nusinersen [17%]) died within the first year of treatment. At 2 years posttreatment, 1 of the 11 surviving patients treated with gene therapy (9%) required nutritional support vs 5 of 10 (50%) treated with nusinersen, and nocturnal ventilation was required in 5 of 11 (45%) receiving gene therapy vs 8 of 10 (80%) receiving nusinersen. Motor outcomes were comparable between groups (mean [SE] intrapair difference in CHOP-INTEND score evolution, -1.69 [1.24] points; P = .17). UCR occurred in 8 of 12 patients (67%) receiving nusinersen and 3 of 12 (25%) receiving gene therapy.

Conclusions and relevance: In this comparative effectiveness study of children with SMA1, gene therapy was associated with lower incidence of UCR and fewer supportive care needs vs nusinersen. These exploratory findings warrant confirmation in larger studies.

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来源期刊
JAMA Network Open
JAMA Network Open Medicine-General Medicine
CiteScore
16.00
自引率
2.90%
发文量
2126
审稿时长
16 weeks
期刊介绍: JAMA Network Open, a member of the esteemed JAMA Network, stands as an international, peer-reviewed, open-access general medical journal.The publication is dedicated to disseminating research across various health disciplines and countries, encompassing clinical care, innovation in health care, health policy, and global health. JAMA Network Open caters to clinicians, investigators, and policymakers, providing a platform for valuable insights and advancements in the medical field. As part of the JAMA Network, a consortium of peer-reviewed general medical and specialty publications, JAMA Network Open contributes to the collective knowledge and understanding within the medical community.
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