Is overnight treatment conversion from tetrabenazine to deutetrabenazine safe in patients with Huntington disease?
In this open-label, single-arm study, 37 patients with chorea associated with Huntington disease switched overnight from a stable, therapeutic tetrabenazine regimen to deutetrabenazine. Deutetrabenazine was generally safe and well tolerated, with chorea scores maintained at the end of week 1 of deutetrabenazine therapy and improved at week 8.
Chorea control may be safely maintained after an overnight switch from tetrabenazine to deutetrabenzine.
Tetrabenazine is efficacious for chorea control; however, tolerability concerns exist. Deutetrabenazine, a novel molecule that reduces chorea, was well tolerated in a double-blind, placebo-controlled study.
To evaluate the safety and explore the efficacy of conversion from tetrabenazine to deutetrabenazine in patients with chorea associated with Huntington disease (HD).
Design, Setting, and Participants
In this ongoing, open-label, single-arm study that started on December 21, 2013, 37 patients at 13 Huntington Study Group sites in the United States and Australia who were taking stable doses of tetrabenazine that provided a therapeutic benefit were switched overnight to deutetrabenazine therapy. After week 1, the deutetrabenazine dose was titrated on a weekly basis for optimal chorea control.
Deutetrabenazine administration at a dosage thought to provide comparable systemic exposure to the active metabolites of the prior, stable tetrabenazine regimen.
Main Outcomes and Measures
Safety measures included adverse events (AEs), clinical laboratory tests, vital signs, electrocardiograms, and validated scales. Changes in the Unified Huntington’s Disease Rating Scale total maximal chorea score and total motor score were efficacy end points.
Of the 53 patients with HD screened for the study, 37 ambulatory patients with manifest HD (mean [SD] age, 52.4 [11.5] years; 22 [59%] male and 15 [41%] female; 36 white [97.3%]) were enrolled. Deutetrabenazine was generally well tolerated, with low rates of neuropsychiatric AEs. Safety scales did not reveal subclinical toxicity with deutetrabenazine treatment. Rates of dose reduction or suspension attributable to AEs were also low. Chorea control, as measured by the total maximal chorea score, was maintained at week 1 and significantly improved at week 8 (mean [SD] change from baseline, 2.1 [3.2]; P < .001).
Conclusions and Relevance
In patients with chorea, overnight conversion to deutetrabenazine therapy provided a favorable safety profile and effectively maintained chorea control.
Frank S, Stamler D, Kayson E, Claassen DO, Colcher A, Davis C, Duker A, Eberly S, Elmer L, Furr-Stimming E, Gudesblatt M, Hunter C, Jankovic J, Kostyk SK, Kumar R, Loy C, Mallonee W, Oakes D, Scott BL, Sung V, Goldstein J, Vaughan C, Testa CM, for the Huntington Study Group/Alternatives for Reducing Chorea in Huntington Disease Investigators. Safety of Converting From Tetrabenazine to Deutetrabenazine for the Treatment of Chorea. JAMA Neurol. Published online July 10, 2017. doi:10.1001/jamaneurol.2017.1352