杜兴氏肌肉萎缩症患者丧失行走能力的预测因素:系统回顾与元分析

IF 3.2 4区 医学 Q2 CLINICAL NEUROLOGY Journal of neuromuscular diseases Pub Date : 2024-04-22 DOI:10.3233/jnd-230220
E. Landfeldt, A. Alemán, S. Abner, R. Zhang, C. Werner, I. Tomazos, N. Ferizovic, H. Lochmüller, J. Kirschner
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引用次数: 0

摘要

研究目的本研究旨在描述杜氏肌营养不良症(DMD)患者丧失行动能力的预测因素。研究方法本系统综述和荟萃分析包括检索 2000 年 1 月 1 日至 2022 年 12 月 31 日期间的 MEDLINE ALL、Embase 和 Cochrane 系统综述数据库,以了解 DMD 运动能力丧失的预测因素。检索词包括作为医学主题词或自由文本词的 "杜兴氏肌营养不良症",以及 "预测因子 "的各种变体。偏倚风险采用纽卡斯尔-渥太华量表进行评估。通过拟合共效逆方差模型,我们对糖皮质激素(与不使用糖皮质激素治疗相比)效果的危险比进行了荟萃分析。结果通过文献检索,共纳入了来自欧洲、亚洲和北美 17 个国家的 45 项关于 DMD 儿童和成人患者的研究。糖皮质激素治疗与延迟丧失行动能力有关(总体荟萃分析 HR deflazacort/泼尼松龙/泼尼松龙:0.44 [95% CI:0.40-0.48])(n = 25 项研究)。首发体征或症状出现较早、发育里程碑丧失较早、基线6MWT较低(即<350米与≥350米和<330米与≥330米)以及基线NSAA较低与丧失行走能力较早相关(n = 5项研究)。外显子3-7缺失、近端突变(上游内含子44)、单个外显子45缺失以及可跳过外显子8、外显子44和外显子53的突变与行走时间延长有关;远端突变(内含子44和下游)、外显子49-50缺失以及可跳过外显子45和外显子51的突变与较早丧失行走能力有关(n = 13项研究)。CD40 基因 rs1883832、LTBP4 基因 rs10880、SPP1 基因 rs2835709 和 rs11730582、TCTEX1D1 基因 rs1060575(n = 7 项研究)中的特定单核苷酸多态性以及种族/民族和家庭/患者贫困程度(n = 3 项研究)与丧失行动能力有关。使用阿塔卢仑(n = 2 项研究)和依替普利岑(n = 3 项研究)治疗与步行时间延长有关。磁共振生物标志物(MRI 和 MRS)被认为是丧失行动能力的重要预测因素(6 项研究)。总共有 33% 的研究存在一定的偏倚风险。结论我们对 DMD 运动能力丧失的预测因素进行的综合分析有助于了解疾病的自然史,并为设计针对这一负担沉重的患者群体的新型疗法的新试验提供信息。
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Predictors of Loss of Ambulation in Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis
Objective: The objective of this study was to describe predictors of loss of ambulation in Duchenne muscular dystrophy (DMD). Methods: This systematic review and meta-analysis included searches of MEDLINE ALL, Embase, and the Cochrane Database of Systematic Reviews from January 1, 2000, to December 31, 2022, for predictors of loss of ambulation in DMD. Search terms included “Duchenne muscular dystrophy” as a Medical Subject Heading or free text term, in combination with variations of the term “predictor”. Risk of bias was assessed using the Newcastle–Ottawa Scale. We performed meta-analysis pooling of hazard ratios of the effects of glucocorticoids (vs. no glucocorticoid therapy) by fitting a common-effect inverse-variance model. Results: The bibliographic searches resulted in the inclusion of 45 studies of children and adults with DMD from 17 countries across Europe, Asia, and North America. Glucocorticoid therapy was associated with delayed loss of ambulation (overall meta-analysis HR deflazacort/prednisone/prednisolone: 0.44 [95% CI: 0.40–0.48]) (n = 25 studies). Earlier onset of first signs or symptoms, earlier loss of developmental milestones, lower baseline 6MWT (i.e.,<350 vs. ≥350 metres and <330 vs. ≥330 metres), and lower baseline NSAA were associated with earlier loss of ambulation (n = 5 studies). Deletion of exons 3–7, proximal mutations (upstream intron 44), single exon 45 deletions, and mutations amenable of skipping exon 8, exon 44, and exon 53, were associated with prolonged ambulation; distal mutations (intron 44 and downstream), deletion of exons 49–50, and mutations amenable of skipping exon 45, and exon 51 were associated with earlier loss of ambulation (n = 13 studies). Specific single-nucleotide polymorphisms in CD40 gene rs1883832, LTBP4 gene rs10880, SPP1 gene rs2835709 and rs11730582, and TCTEX1D1 gene rs1060575 (n = 7 studies), as well as race/ethnicity and level of family/patient deprivation (n = 3 studies), were associated with loss of ambulation. Treatment with ataluren (n = 2 studies) and eteplirsen (n = 3 studies) were associated with prolonged ambulation. Magnetic resonance biomarkers (MRI and MRS) were identified as significant predictors of loss of ambulation (n = 6 studies). In total, 33% of studies exhibited some risk of bias. Conclusion: Our synthesis of predictors of loss of ambulation in DMD contributes to the understanding the natural history of disease and informs the design of new trials of novel therapies targeting this heavily burdened patient population.
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来源期刊
Journal of neuromuscular diseases
Journal of neuromuscular diseases Medicine-Neurology (clinical)
CiteScore
5.10
自引率
6.10%
发文量
102
期刊介绍: The Journal of Neuromuscular Diseases aims to facilitate progress in understanding the molecular genetics/correlates, pathogenesis, pharmacology, diagnosis and treatment of acquired and genetic neuromuscular diseases (including muscular dystrophy, myasthenia gravis, spinal muscular atrophy, neuropathies, myopathies, myotonias and myositis). The journal publishes research reports, reviews, short communications, letters-to-the-editor, and will consider research that has negative findings. The journal is dedicated to providing an open forum for original research in basic science, translational and clinical research that will improve our fundamental understanding and lead to effective treatments of neuromuscular diseases.
期刊最新文献
A Likely Pathogenic variant in the KBTBD13 Gene: A Case Series of Three Patients with Nemaline Myopathy Type 6. An International Retrospective Early Natural History Study of LAMA2-Related Dystrophies. Life Expectancy and Causes of Death in Patients with Myotonic Dystrophy Type 2. E-Health & Innovation to Overcome Barriers in Neuromuscular Diseases. Report from the 3rd eNMD Congress: Pisa, Italy, 29-30 October 2021. Predictors of Loss of Ambulation in Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis
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