{"title":"Safety and Efficacy of Givinostat for Patients with Muscular Dystrophy: A Systematic Review.","authors":"Prasanjit Das, Bisweswar Ojha, Alapan Das, Bhairav Kumar Pathak, Kaushik Mukhopadhyay","doi":"10.1159/000547936","DOIUrl":null,"url":null,"abstract":"<p><p><p>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 inhibitors (i.e., givinostat) is a recently approved therapy for DMD. In this systematic review, we aimed to evaluate givinostat in MD patients regarding safety and efficacy.</p><p><strong>Methods: </strong>A systematic review was performed according to the PRISMA guidelines by searching through Medline, Embase, Cochrane Library, and Web of Science. Only randomized control trials 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.</p><p><strong>Results: </strong>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 diarrhoea, thrombocytopenia, and hypertriglyceridemia, leading to dose reductions, though no new safety signals or treatment-related deaths were observed.</p><p><strong>Conclusion: </strong>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. Givinostat offers potential as a disease-modifying therapy for DMD but requires further investigation to establish its role in BMD. </p>.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"347-359"},"PeriodicalIF":2.8000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503821/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000547936","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/14 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
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 inhibitors (i.e., givinostat) is a recently approved therapy for DMD. In this systematic review, we aimed 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 randomized control trials 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 diarrhoea, thrombocytopenia, and hypertriglyceridemia, leading to dose reductions, though no new safety signals or treatment-related deaths were observed.
Conclusion: 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. Givinostat offers potential as a disease-modifying therapy for DMD but requires further investigation to establish its role in BMD.
简介：肌营养不良症（MD）是指一组导致骨骼肌进行性无力和变性的遗传性疾病。其中，杜氏肌营养不良症（DMD）和贝克尔肌营养不良症（BMD）是最常见的类型。组蛋白去乙酰化酶（HDAC）抑制剂Givinostat)是最近批准的治疗DMD的药物。在这篇系统综述中，我们旨在评估吉维诺他在MD患者中的安全性和有效性。方法：根据PRISMA指南，检索Medline、Embase、Cochrane Library和Web of Science进行系统评价。仅包括比较吉维司他与安慰剂或其他治疗的随机对照试验。主要结果是运动功能改变和组织病理学肌肉改变，次要结果是不良反应。结果：共纳入188份文献，经筛选，有2项临床试验符合纳入标准。在DMD患者中，Givinostat显著减缓疾病进展，改善4次爬楼梯次数（p=0.037），减少肌肉脂肪浸润。在BMD患者中，纤维化进展无显著差异（p=0.8282），但MRI显示肌肉脂肪替代减少。常见的不良事件包括腹泻、血小板减少和高甘油三酯血症，导致剂量减少，但没有观察到新的安全性信号或治疗相关死亡。讨论：吉维司他似乎在减缓DMD的疾病进展方面有效，但在BMD方面几乎没有益处。它的安全状况需要严格监控。疗效差异可能与疾病的病理生理及进展速度有关。有必要进行更大规模和更长时间的随访试验，以确认长期益处并优化给药策略。结论：吉维司他作为一种潜在的DMD疾病改善疗法，但需要进一步研究以确定其在BMD中的作用。
期刊介绍：
''Pharmacology'' is an international forum to present and discuss current perspectives in drug research. The journal communicates research in basic and clinical pharmacology and related fields. It covers biochemical pharmacology, molecular pharmacology, immunopharmacology, drug metabolism, pharmacogenetics, analytical toxicology, neuropsychopharmacology, pharmacokinetics and clinical pharmacology. In addition to original papers and short communications of investigative findings and pharmacological profiles the journal contains reviews, comments and perspective notes; research communications of novel therapeutic agents are encouraged.
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