Objective: To assess the safety and efficacy of vesicular monoamine transporter 2 (VMAT2) inhibitors (deutetrabenazine, tetrabenazine, valbenazine) in managing chorea in Huntington’s Disease (HD).

Background: Chorea leads to motor function abnormalities in HD, which result in independence. Even though VMAT2 inhibitors are used for treatment, their efficacy and safety are still in question. Accordingly, this meta-analysis will include the latest evidence from RCTs evaluating the use of these drugs for HD chorea.

Method: According to Prisma guidelines, we reviewed Scopus, PubMed, and Embase for RCTs comparing VMAT2 inhibitors to placebo. Total Maximal chorea (TMC) score change from the UHDRS chorea subscale was the primary measure, and the secondary measure was Clinical Global Impression of Change (CGI-C) and fatigue as a side effect. Random effects model was used for data synthesis and Risk of Bias 2 (ROB2) for quality assessment. Sensitivity analysis was performed to resolve any heterogeneity.

Results: Three RCTs were included (N=301 patients) in the analysis. VMAT2 inhibitors significantly improved chorea severity in a mean difference of -3.06 (95% CI: -3.88 to -2.25, P < 0.00001, I² = 65%). Following sensitivity analysis, the heterogeneity was resolved (I² = 0%, mean difference: -3.48, 95% CI: -3.76 to -3.21). CGI-C scores stated that VMAT2 inhibitors lead to clinical improvement, with 5.5-fold increased odds (OR: 5.50, 95% CI: 3.13–9.68, P < 0.00001). The most common side effect, which is fatigue, didn’t show any statistical difference compared to placebo (OR: 1.67, 95% CI: 0.74–3.78, P = 0.22). Low risk of bias was shown in all studies.

Conclusion: VMAT inhibitors effectively enhance chorea motor symptoms in HD, with notable CGI-C improvement. safety is considered acceptable, with fatigue being the most common side effect, but not significantly more prominent than placebo. Regardless of the restricted number of RCTs, this meta-analysis shows strong comparative evidence regarding VMAT2 inhibitors data available in the literature. Plans should concentrate on understanding long-term tolerability and investigate deep comparisons among specific VMAT2 inhibitors to update treatment plans.

Figuere 1 :UHDRS TMC

Figure 2 : CGI-C Scale

Figure 3 : Fatigue

References: [1] S. Frank et al., “Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease: A Randomized Clinical Trial,” JAMA, vol. 316, no. 1, pp. 40–50, Jul. 2016, doi: 10.1001/JAMA.2016.8655.
[2] F. J. Marshall, “Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial,” Neurology, vol. 66, no. 3, pp. 366–372, Feb. 2006, doi: 10.1212/01.WNL.0000198586.85250.13.
[3] E. F. Stimming et al., “Safety and efficacy of valbenazine for the treatment of chorea associated with Huntington’s disease (KINECT-HD): a phase 3, randomised, double-blind, placebo-controlled trial,” Lancet Neurol, vol. 22, no. 6, pp. 494–504, Jun. 2023, doi: 10.1016/S1474-4422(23)00127-8.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/comparative-efficacy-and-safety-of-vmat2-inhibitors-for-chorea-in-huntingtons-disease-a-systematic-review-and-meta-analysis/