Deutetrabenazine treatment outcomes with doses above U.S. Food and Drug Administration maximum approved doses in Huntington's disease chorea: A dual-site analysis

BackgroundDeutetrabenazine, a vesicular monoamine transporter 2 inhibitor, is one of few treatment options available for Huntington's disease (HD) chorea. There is limited data describing clinical experience with deutetrabenazine doses >48 mg daily.ObjectiveDescribe treatment outcomes for deutetrabenazine >48 mg daily.MethodsA dual site retrospective cohort study of patients on deutetrabenazine titrated to doses >48 mg/day for HD chorea from April 2017 through December 2021 was conducted. Patients using concomitant strong CYP2D6 inhibitors at time of deutetrabenazine initiation, those who became deceased or lost to follow-up within six months of dose increase above 48 mg/day, or previously enrolled in a study on >48 mg daily and moving to commercial product were excluded. Outcomes were reported descriptively including therapeutic response, adverse effects (AEs), adherence (measured by proportion of days covered [PDC]), and discontinuation.ResultsThirty patients were included: 47% female, 93% White, median age 56 years. Most patients required dose escalations for inadequate response. The rate of AEs reported before and after transitioning to doses >48 mg/day was the same. Psychiatric changes were less commonly reported at doses >48 mg/day, but extrapyramidal symptoms were more common. The median total maximum chorea score in the Unified HD Rating Scale was 13 (IQR 9-19) and 13 (IQR 7-18) at baseline and follow-up, respectively. Median PDC was 0.99 (IQR 0.94-1.00); two patients discontinued therapy due to AEs.ConclusionsDeutetrabenazine >48 mg daily appears safe and well tolerated in patients with uncontrolled HD chorea, though no significant change in total maximal chorea score was found.