Objective: To evaluate long-term deutetrabenazine safety on motor, psychiatric, and cognitive measures in participants with chorea associated with Huntington disease (HD).

Background: Deutetrabenazine, a vesicular monoamine transporter 2 inhibitor, is US FDA approved for treatment of chorea in HD, and has been shown to reduce chorea with a favorable safety profile in the 12‑week pivotal trial First-HD (NCT01795859) and the long-term open-label extension study ARC-HD (NCT01897896).

Method: ARC-HD, a 3-year study, included participants who completed First-HD (Rollover Cohort) and participants who converted overnight from tetrabenazine (Switch Cohort). Safety motor measures were assessed with Unified HD Rating Scale (UHDRS) Parkinsonism subscore, UPDRS dysarthria item, Swallowing Disturbance Questionnaire (SDQ), and Barnes Akathisia Rating Scale (BARS). Psychiatric and cognitive safety were assessed with Hospital Anxiety and Depression Scale (HADS), Montreal Cognitive Assessment (MoCA), Epworth Sleepiness Scale (ESS), and Columbia Suicide Severity Rating Scale (C-SSRS). For all assessments except MoCA, higher score indicates greater impairment.

Results: Overall, 119 participants enrolled in ARC-HD (Rollover Cohort, n=82; Switch Cohort, n=37). Mean (SD) change from baseline to week 145 for motor measures from the Rollover and Switch cohorts were: UHDRS parkinsonism, 3.6 (4.57) and 2.4 (5.39), respectively; UPDRS dysarthria, 0.7 (0.68) and 0.6 (0.98); SDQ, 3.8 (5.88) and 6.6 (10.86); BARS summary, –0.2 (1.25) and –0.2 (2.81); and BARS global, –0.1 (0.70) and 0.1 (1.51). Mean (SD) change from baseline to week 145 for psychiatric and cognitive measures in the Rollover and Switch cohorts were: HADS anxiety, 1.7 (3.68) and –0.8 (5.76), respectively; HADS depression, 3.2 (4.76) and 0.3 (4.98); MoCA, –2.3 (4.01) and –1.8 (4.26); and ESS, 2.2 (5.13) and 1.7 (7.25). Prior to treatment, C-SSRS results for Rollover and Switch cohorts were: suicidal ideation, 15.9% and 10.8%; and suicidal behavior, 1.2% and 0%, respectively. During the treatment period, C‑SSRS results for Rollover and Switch Cohorts were: suicidal ideation, 13.6% and 10.8%; and suicidal behavior, 3.7% and 2.7%.

Conclusion: Over 3 years, deutetrabenazine was generally well tolerated with respect to motor safety, anxiety, depression, cognition, and sleepiness measures.

References: Previous presentation:
Frank S, Stamler D, Vaughan C, et al. Effects of long-term deutetrabenazine treatment on motor safety outcomes in chorea associated with Huntington’s disease. Presented at: 28th Annual Meeting of the Huntington Study Group; November 4–6, 2021; Virtual.
Frank S, Stamler D, Vaughan C, et al. Effects of long-term deutetrabenazine treatment on psychiatric and cognitive safety outcomes in chorea associated with Huntington’s disease. Presented at: 28th Annual Meeting of the Huntington Study Group; November 4–6, 2021; Virtual.

« Back to 2022 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/long-term-deutetrabenazine-safety-on-motor-psychiatric-and-cognitive-measures-in-individuals-with-chorea-associated-with-huntington-disease/