Safety and Efficacy of Long‐Term Deutetrabenazine Use in Children and Adolescents with Tics Associated with Tourette Syndrome: An Open‐Label Extension Study

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and phonic tics. OBJECTIVE: To assess the safety and efficacy of deutetrabenazine (Teva Neuroscience, Inc, Parsippany, NJ), a vesicular monoamine transporter 2 inhibitor, in children and adolescents with TS. METHODS: Alternatives for Reducing Tics in TS (ARTISTS) open‐label extension (OLE) (NCT03567291) was a 54‐week, global, phase 3, open‐label extension study of deutetrabenazine (6–48 mg daily) conducted May 28, 2018 to April 3, 2020 with a 2‐week randomized withdrawal period. Participants (6–16 years of age) had TS and active tics causing distress or impairment. Safety (primary outcome) was assessed by treatment‐emergent adverse events (TEAEs) and clinical laboratory testing. Efficacy was measured by the Yale Global Tic Severity Scale‐Total Tic Score (YGTSS‐TTS). RESULTS: The intent‐to‐treat population (228 participants; mean age, 12.0 years; 79.8% male; 86.4% white) had a median (range) duration of exposure of 28.4 (0.3–52.9) weeks. Of 227 participants in the safety analysis, 161 (70.9%) reported ≥1 TEAE (exposure‐adjusted incidence rate, 2.77/patient‐year), of which 95 (41.9%) were treatment related. The most frequently reported TEAEs were headaches, somnolence, nasopharyngitis, weight increases, and anxiety. No additional safety signals were observed. Worsening of YGTSS‐TTS after the 2‐week randomized withdrawal was not statistically significant (least squares mean difference, −0.4; P = 0.78). Several exploratory measures showed sustained improvement throughout the treatment periods. CONCLUSIONS: In this long‐term, open‐label trial, deutetrabenazine was well tolerated with low frequency of TEAEs. There was no significant difference in tics between treatment arms during the 2‐week randomized withdrawal period, however, descriptive statistics and comparison with baseline showed a numeric improvement in tics, quality of life, and other measures.