Supplementary Material for: Safety and Efficacy of Givinostat for patients with Muscular dystrophy: A Systematic review

Introduction: Muscular dystrophy(MD) refers to a group of genetic disorders leading to progressive weakness and degeneration of skeletal muscle. Among them, Duchenne muscular dystrophy(DMD) and Becker muscular dystrophy(BMD) are the most common types. Histone deacetylase(HDAC) inhibitors(i.e. Givinostat) are a recently approved therapy for DMD. In this systematic review, we aim to evaluate Givinostat in MD patients regarding safety and efficacy.
Methods: A systematic review was performed according to the PRISMA guidelines by searching through Medline, Embase, Cochrane Library and Web of Science. Only RCT comparing Givinostat vs placebo or other therapies are included. The primary outcomes were motor function alteration and histopathologic muscle changes and the secondary outcomes were the adverse reactions.
Results: A total of 188 records were identified, and after screening, two clinical trials met the inclusion criteria. In DMD patients, Givinostat significantly slowed disease progression, improving four stair-climb times (p=0.037) and reducing muscle fat infiltration. In BMD patients, fibrosis progression was not significantly different (p=0.8282), but MRI showed reduced muscle fat replacement. Common adverse events included diarrhea, thrombocytopenia, and hypertriglyceridemia, leading to dose reductions, though no new safety signals or treatment-related deaths were observed.
Discussion: Givinostat seems to be effective in slowing disease progression in DMD but has little benefit in BMD. Its safety profile requires rigorous monitoring. Efficacy difference might be explained by the pathophysiology of the disease and the progression rate. Larger and longer follow-up trials are warranted to confirm longer term benefits and to optimize dosing strategies.
Conclusion: Givinostat offers potential as a disease-modifying therapy for DMD but requires further investigation to establish its role in BMD.

引言：肌营养不良症（Muscular Dystrophy, MD）是一类以进行性骨骼肌无力与退变为特征的遗传性疾病，其中杜氏肌营养不良症（Duchenne Muscular Dystrophy, DMD）与贝克型肌营养不良症（Becker Muscular Dystrophy, BMD）为最常见的亚型。组蛋白去乙酰化酶（Histone Deacetylase, HDAC）抑制剂（如吉维诺司他）是新近获批用于DMD治疗的药物。本系统综述旨在评估吉维诺司他用于MD患者的安全性与有效性。
方法：本研究依据PRISMA指南开展系统综述，通过检索Medline、Embase、Cochrane Library及Web of Science数据库获取文献。仅纳入吉维诺司他与安慰剂或其他疗法对比的随机对照试验（Randomized Controlled Trial, RCT）。主要结局指标为运动功能改变与组织病理学肌肉改变，次要结局指标为不良反应。
结果：本研究共检索到188条文献记录，经筛选后最终有2项临床试验符合纳入标准。在DMD患者中，吉维诺司他可显著延缓疾病进展，改善四次爬楼梯测试时间（P=0.037）并降低肌肉脂肪浸润程度。在BMD患者中，纤维化进展无显著差异（P=0.8282），但磁共振成像（Magnetic Resonance Imaging, MRI）结果显示肌肉脂肪替代程度有所降低。常见不良反应包括腹泻、血小板减少症与高甘油三酯血症，可导致剂量调整，但未观察到新的安全信号或与治疗相关的死亡病例。
讨论：吉维诺司他可有效延缓DMD患者的疾病进展，但对BMD患者获益有限。其安全性特征需进行严格监测。疗效差异或可通过疾病的病理生理机制及进展速度予以解释。未来需开展更大样本量、更长随访周期的临床试验，以验证其长期获益并优化给药方案。
结论：吉维诺司他有望成为DMD的疾病修饰治疗药物，但仍需进一步研究以明确其在BMD治疗中的应用价值。