Efficacy and Safety of Fixed-Dose Deutetrabenazine in Children and Adolescents for Tics Associated With Tourette Syndrome

Abstract

IMPORTANCE Tourette syndrome is a neurodevelopmental disorder characterized by childhood onset of motor and phonic tics, often accompanied by behavioral and psychiatric comorbidities.Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor approved in the US for the treatment of chorea associated with Huntington disease and tardive dyskinesia. OBJECTIVETo report results of the ARTISTS 2 (Alternatives for Reducing Tics in Tourette Syndrome 2) study examining deutetrabenazine for treatment of Tourette syndrome. DESIGN, SETTING, AND PARTICIPANTS This phase 3, randomized, double-blind, placebocontrolled, parallel-group, fixed-dose study was conducted over 8 weeks with a 1-week follow-up (June 21, 2018, to December 9, 2019). Children and adolescents aged 6 to 16 years with a diagnosis of Tourette syndrome and active tics causing distress or impairment were enrolled in the study. Children were recruited from 52 sites in 10 countries. Data were analyzed from February 4 to April 22, 2020. INTERVENTIONS Participants were randomized (1:1:1) to low-dose deutetrabenazine (up to 36 mg/d), high-dose deutetrabenazine (up to 48 mg/d), or a matching placebo, which were titrated over 4 weeks to the target dose followed by a 4-week maintenance period. MAIN OUTCOMES AND MEASURES The primary efficacy end point was change from baseline to week 8 in the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) for high-dose deutetrabenazine. Key secondary end points included changes in 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. Safety assessments included incidence of treatment-emergent adverse events, laboratory parameters, vital signs, and questionnaires. RESULTSThe study included 158 children and adolescents (mean [SD] age, 11.7 [2.6] years). A total of 119 participants (75%) were boys; 7 (4%), Asian; 1 (1%), Black; 32 (20%), Hispanic; 4 (3%), Native American; 135 (85%), White; 2 (1%), multiracial; 9 (6%), other race; and 1 (0.6%), of unknown ethnic origin. Fifty-two participants were randomized to the high-dose deutetrabenazine group, 54 to the low-dose deutetrabenazine group, and 52 to the placebo group. Baseline characteristics for participants were similar between groups. Of the total 158 participants, 64 (41%) were aged 6 to 11 years, and 94 (59%) were aged 12 to 16 years at baseline. Mean time since Tourette syndrome diagnosis was 3.3 (2.8) years, and mean baseline YGTSS-TTS was 33.8 (6.6) points. At week 8, the difference in YGTSS-TTS was not significant between the high-dose deutetrabenazine and placebo (continued) Key Points Question Are fixed doses of deutetrabenazine up to 48 mg per day safe and effective for the treatment of tics associated with Tourette syndrome in pediatric patients? Findings In this randomized clinical trial of 158 children and adolescents, differences in tic severity b...

Tourette syndrome research highlights from 2021

“…To date, the mother compound, tetrabenazine, has been used largely off label for tic treatment in the absence of evidence derived from high quality clinical studies. Alas, both deutetrabenazine 90 , 91 and valbenazine failed to meet primary endpoints in their respective studies. 92 …”

“…To date, the mother compound, tetrabenazine, has been used largely off label for tic treatment in the absence of evidence derived from high quality clinical studies. Alas, both deutetrabenazine 90,91 and valbenazine failed to meet primary endpoints in their respective studies. 92 An interesting case series described six children or adolescents with aggressive behaviors in whom lurasidone, a novel antipsychotic, was added to either aripiprazole or risperidone; the addition of lurasidone appeared to diminish these symptoms with good tolerability.…”

The French version of the Gilles de la Tourette Syndrome Quality of Life Scale for adolescents (GTS-QOL-French-Ado): Adaptation and psychometric evaluation

“…Further evaluation of the psychometric properties of the GTS-QOL-French-Ado are needed on larger samples to confirm our first results, and notably its five-factor structure. However, to our knowledge, our study, using a specific HRQoL instrument, is one of those including the higher number of adolescents with GTS [ 4 , 49 , 56 – 60 ].…”

“…However, to our knowledge, our study, using a specific HRQoL instrument, is one of those including the higher number of adolescents with GTS [4,49,[56][57][58][59][60].…”

Emerging therapies and recent advances for Tourette syndrome

“…Participants were given either a low (up to 36 mg) or high (up to 48 mg) dose of deutetrabenazine or placebo. Both the high dose and low dose group did not reach the primary endpoint to demonstrate reductions in YGTSS-TTS ( p = 0.600 and p = 0.474 respectively) [ 62 ]. The most common TEAEs were somnolence, headache, and nasopharyngitis [ 62 ].…”