Deutetrabenazine failed to meet the primary efficacy end point for the treatment of Tourette syndrome (TS) among children and adolescents. These findings, from a phase 2/3, randomized, double-masked, placebo-controlled, parallel-group, dose-titration study, were published in JAMA Network Open.
The ARTISTS 1 study recruited patients (N=119) aged 6-16 years with TS at 36 centers in six countries across Europe and North America between 2018 and 2019. Stratified by age, patients were randomized in a 1:1 ratio to receive deutetrabenazine (n=59) or placebo (n=60) for 12 weeks.
The dosage was initiated at 6 mg/d and was titrated over 7 weeks on the basis of body weight and cytochrome P450 2D6 impairment status. After a 1 week washout period, the primary outcome was change in Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS).
The intervention and control cohorts were aged mean 11.5 (standard deviation [SD], 2.5) and 11.5 (SD, 2.6) years, 90% and 85% were boys, 83% and 88% were White, 81% and 67% had a history of psychiatric disorders, and 53% and 43% were receiving TS treatment, respectively. The baseline YGTSS-TTS score was an average of 32.3 (SD, 5.9).
At 12 weeks, YGTSS-TTS decreased from baseline by -9.1 (SD, 1.28) among the deutetrabenazine and -8.4 (SD, 1.25) among the placebo recipients (P =.69).
Similarly, there was no significant group differences in the scores for the TS-Clinical Global Impression (P =.85), the TS-Patient Global Impression Impact (P =.05), or the Child and Adolescent Gilles de la TS-Quality of Life Activities of Daily Living (P =.73).
Treatment-emergent adverse events were reported by 65.5% of deutetrabenazine and 55.9% of placebo recipients. Events were mild or moderate in severity. No additional safety concerns beyond current labeling were observed. Adverse events were more frequently reported during the titration period (57%) than during the maintenance period (26%). Events in the suicide/self-injury realm were reported by 1 deutetrabenazine and 3 placebo recipients.
This study was limited by the primary outcome, tic, which has been shown in previous studies to be difficult to capture response due to its frequency and intensity.
This study did not find a significant effect on tics from deutetrabenazine among pediatric patients with TS.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Jankovic J, Coffey B, Claassen DO, et al. Safety and efficacy of flexible-dose deutetrabenazine in children and adolescents with Tourette Syndrome: a randomized clinical trial. JAMA Netw Open. Published online October 5, 2021. doi:10.1001/jamanetworkopen.2021.28204