OBJECTIVES : Huntington’s disease (HD) is a rare, progressive, genetic neurodegenerative disorder. Chorea is the most common motor symptom of HD. We reviewed the clinical evidence of two approved vesicular monoamine transporter type-2 (VMAT2) inhibitors tetrabenazine and deutetrabenazine for the treatment of chorea in HD.

METHODS : A focused search of published literature was performed using Embase^® and MEDLINE^® from database inception to February 2020 to identify the studies assessing tetrabenazine and deutetrabenazine in HD patients. The meta-analyses were performed to compare the efficacy (Unified HD Rating Scale [UHDRS] total maximal chorea [TMC] score, motor scores, and patients (%) with Clinical Global Impression of Change [CGIC] improvement), safety, and tolerability of VMAT2-inhibitors against placebo using Stata software. Further, an indirect treatment comparison (ITC) was also conducted between tetrabenazine and deutetrabenazine.

RESULTS : Two double-blind, placebo-controlled, 12-week trials met the inclusion criteria. Both trials were performed by the same study group and were broadly similar in terms of methodological and clinical characteristics except UHDRS score requirements at baseline (≥10 vs. ≥8). VMAT2-inhibitors were associated with significantly better efficacy in terms of reducing UHDRS-TMC scores (mean difference [MD]:-2.83; 95%Confidence Interval [CI]:-3.80 to -1.86) and motor scores (MD:-3.78; 95%CI:-5.81 to -1.75) vs. placebo. The CGIC treatment success (proportion of patients with much or very much improvement) was significantly high with VMAT2-inhibitors vs. placebo (Odds ratio [OR]: 6.09; 95%CI: 2.57 to 14.42). Further, an ITC indicated comparable efficacy, safety, and tolerability of both treatments except dose reductions due to adverse events (DR-AEs). DR-AEs were significantly lower in deutetrabenazine as compared to tetrabenazine (OR: 0.04; 95%CI:0, 0.61).

CONCLUSIONS : Tetrabenazine and deutetrabenazine significantly ameliorated the chorea burden. In the absence of head to head studies, indirect comparisons signify comparable efficacy and safety of both agents for the treatment of Huntington chorea.