1. No significant differences in tic severity were found between deutetrabenazine and placebo after 8 weeks of treatment, despite a numeric improvement at the end of the titration period.
2. Deutetrabenazine was well tolerated after 8 weeks of treatment, with no evidence of any new safety signals for increased risk of depression or suicidality.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Tourette syndrome is a neurodevelopmental movement disorder characterized by childhood onset of motor and phonic tics. Currently, the only medications approved by the US Food and Drug Administration are dopamine-receptor antagonists including haloperidol, pimozide, and aripiprazole, however, there are significant concerns around their safety/side effect profile in the pediatric population. Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor currently used for the treatment of chorea associated with Huntington disease and tardive dyskinesia, where its efficacy for the treatment of childhood tics is unknown. This phase 3, placebo-controlled ARTISTS 2 trial evaluated the efficacy and safety of fixed doses of deutetrabenazine in reducing symptoms of motor and phonic tics associated with Tourette syndrome in pediatric patients. The main endpoint was change in motor and behavioral function from baseline to week 8 assessed using the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) for high-dose deutetrabenazine. Secondary endpoints included changes on YGTSS-TTS for low-dose deutetrabenazine, Tourette Syndrome Clinical Global Impression score, Tourette Syndrome Patient Global Impression of Impact score, and Child and Adolescent Gilles de la Tourette Syndrome-Quality of Life Activities of Daily Living subscale score. Lastly, treatment-emergent adverse events were assessed to determine the safety profile of fixed-dose deutetrabenazine. Among 158 pediatric patients, no significant differences in tic severity were found between deutetrabenazine and placebo after 8 weeks of treatment, despite initial numeric improvements at the end of the 4-week titration period with similar mild or moderate treatment-emergent adverse events reported across all groups. In this 8-week randomized clinical trial on the efficacy of fixed-dose deutetrabenazine in children and adolescents with Tourette syndrome, the primary efficacy endpoint was not met, with no significant differences between treatment and placebo groups. Overall, deutetrabenazine was well tolerated after 8 weeks of treatment, with no evidence of any new safety signals for increased risk of depression or suicidality. A limitation of this study was that most participants were non-Hispanic Caucasian children, limiting the generalizability of the study findings in a more diverse population.
In-Depth [randomized controlled trial]: This phase 3, randomized, double-blind, placebo-controlled study included 158 children and adolescents (mean [SD] age, 11.7 [2.6] years; 119 [75%] boys; 135 [85%] White, 32 [20%] Hispanic, 7 [4%] Asian). The study took place across 52 centers in 10 countries between June 2018 to December 2019, with analysis completed in April 2020. Children and adolescents aged 6 to 16 years with a diagnosis of Tourette syndrome and active tics were randomized (1:1:1) to low-dose deutetrabenazine (n =54; up to 36 mg/d), high-dose deutetrabenazine (n = 52; up to 48mg/d), or a matching placebo (n = 52), with similar baseline characteristics between groups. Among 158 patients, mean time since Tourette syndrome diagnosis was 3.3 (2.8) years, and mean baseline YGTSS-TTS was 33.8 (6.6) points. After a 4-week titration period followed by a 4-week maintenance period, there was no significant difference in YGTSS-TTS between the high-dose deutetrabenazine and placebo groups (least-squares mean difference, -0.8 points; 95%CI, -3.9 to 2.3 points; P = .60; Cohen d, -0.11). Furthermore, there were no nominally significant differences between groups for key secondary outcomes. Mild or moderate treatment-emergent adverse events were reported in 34 patients (65%) treated with high dose deutetrabenazine, 24 (44%) treated with low-dose deutetrabenazine, and 25 (49%) treated with placebo.
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