Efficacy and Safety of VMAT2 Inhibitors in the Treatment of Huntington Disease: A Meta-Analysis of Randomized Clinical Trials.

IF 3.7 Q3 CLINICAL NEUROLOGY Neurology. Clinical practice Pub Date : 2026-04-01 Epub Date: 2026-01-13 DOI:10.1212/CPJ.0000000000200578

Elder Machado Leite, Armando Leão Lages, José Fernando Barbosa Moura, Adelson Barroso Junior, João Eduardo Silva Lima, José Arnaldo Cavalcanti Amorim, Gustavo Henrique Brasil Rodrigues

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Abstract

Background and objectives: Vesicular monoamine transporter 2 inhibitors (VMAT2is) have demonstrated effectiveness in attenuating motor symptoms of Huntington disease (HD). However, evidence regarding their long-term safety and overall efficacy in this population remains limited. The aim of this study was to investigate the efficacy and safety of VMAT2is in the treatment of HD.

Methods: We performed a meta-analysis of placebo-controlled, randomized controlled trials (RCTs) of VMAT2is in patients with HD. PubMed, Embase, and Cochrane databases were searched for trials up to February 8, 2025. Data were extracted from published reports, and quality assessment was performed per Cochrane recommendations. Binary end points were compared using odds ratios (ORs) while continuous end points were compared using mean difference (MD) and standardized MD (SMD), with 95% CIs for all measures. The analysis end points included changes in the Unified Huntington's Disease Rating Scale-Total Maximal Chorea (UHDRS-TMC), improvements in the Clinical Global Impression of Change (CGI-C), incidence of adverse effects, and alterations in depression scale scores.

Results: Of 336 database results, 3 RCTs and 302 patients were included; 163 (53.97%) received VMAT2is. The UHDRS-TMC (MD -2.98; 95% CI [-4.21 to -1.75]; p = 0.009; I ² = 0%) and CGI-C (OR 5.36; CI 95% [2.94-9.76]; p = 0.007; I ² = 0%) scores were significantly improved in the intervention group. In addition, the therapy did not influence the adverse effects (OR 1.89; CI 95% [0.47-7.70]; p = 0.19 I ² = 28%) and depression scale scores (SMD -0.40; 95% CI [-1.20 to 0.41]; p = 0.17; I ² = 59%).

Discussion: In patients with HD, treatment with VMAT2is improved chorea (UHDRS-TMC and CGI-C), with no significant changes in adverse effects or depressive symptoms. These findings indicate that VMAT2is may be a promising and safe treatment option for the disease.

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VMAT2抑制剂治疗亨廷顿病的疗效和安全性：随机临床试验的荟萃分析

背景和目的：水疱单胺转运蛋白2抑制剂（VMAT2is）已被证明可有效减轻亨廷顿病（HD）的运动症状。然而，关于它们在这一人群中的长期安全性和总体有效性的证据仍然有限。本研究的目的是探讨VMAT2is治疗HD的有效性和安全性。方法：我们对HD患者中vmat2的安慰剂对照、随机对照试验（rct）进行了荟萃分析。检索PubMed、Embase和Cochrane数据库，检索截止到2025年2月8日的试验。数据从已发表的报告中提取，并根据Cochrane推荐进行质量评估。使用比值比（or）比较二元终点，使用平均差（MD）和标准化MD （SMD）比较连续终点，所有测量值的ci均为95%。分析终点包括统一亨廷顿病评定量表-总最大舞蹈症（UHDRS-TMC）的变化、临床总体变化印象（CGI-C）的改善、不良反应的发生率和抑郁量表评分的变化。结果：在336个数据库结果中，纳入3个rct和302例患者；163例（53.97%）接受VMAT2is治疗。干预组UHDRS-TMC （MD -2.98; 95% CI [-4.21 ~ -1.75]; p = 0.009; I 2 = 0%）和CGI-C （OR 5.36; CI 95% [2.94 ~ 9.76]; p = 0.007; I 2 = 0%）评分显著改善。此外，该疗法不影响不良反应（OR 1.89; CI 95% [0.47-7.70]; p = 0.19 i2 = 28%）和抑郁量表评分（SMD -0.40; 95% CI[-1.20至0.41];p = 0.17; i2 = 59%）。讨论：在HD患者中，vmat2治疗可改善舞蹈病（UHDRS-TMC和CGI-C），不良反应或抑郁症状无显著变化。这些发现表明，VMAT2is可能是一种有希望且安全的治疗方案。

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来源期刊

Neurology. Clinical practice CLINICAL NEUROLOGY-

CiteScore

4.00

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0.00%

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期刊介绍： Neurology® Genetics is an online open access journal publishing peer-reviewed reports in the field of neurogenetics. The journal publishes original articles in all areas of neurogenetics including rare and common genetic variations, genotype-phenotype correlations, outlier phenotypes as a result of mutations in known disease genes, and genetic variations with a putative link to diseases. Articles include studies reporting on genetic disease risk, pharmacogenomics, and results of gene-based clinical trials (viral, ASO, etc.). Genetically engineered model systems are not a primary focus of Neurology® Genetics, but studies using model systems for treatment trials, including well-powered studies reporting negative results, are welcome.