Austedo did not significantly reduce tics linked to Tourette syndrome in children

Austedo was generally well tolerated among children and adolescents with Tourette syndrome; however, the efficacy was not significantly different compared with placebo, according to a study in JAMA Network Open.

“[In] this 8-week randomized clinical trial of the efficacy and safety of fixed doses of [Austedo (deutetrabenazine, Teva Pharmaceuticals)] in children and adolescents with Tourette syndrome, the primary efficacy endpoint was not met, despite a numeric improvement at the end of the titration period,” Barbara Coffey, MD, MS, from the University of Miami Miller School of Medicine and colleagues wrote. “Secondary efficacy endpoint results were generally similar to the primary endpoint.”

Coffey and colleagues identified 158 children and adolescents with Tourette syndrome and active tics from 52 sites in 10 countries. There were 54 children randomly assigned to either low-dose deutetrabenazine (up to 36 mg per day), 52 to high-dose deutetrabenazine (up to 48 mg per day), and 52 to the placebo group, who were titrated over 4 weeks to the target dose. Of these patients, 64 were aged 6 to 11 and 94 were aged 12 to 16 years. This was then followed by a 4-week maintenance period. Patients were followed for 1 week. The change from baseline to week 8 in the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) for high-dose deutetrabenazine served as the primary efficacy point. Other endpoints 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.

The incidence of treatment-emergent adverse events (TEAEs), laboratory parameters, vital signs and questionnaires were among the safety assessment included. Investigators noted the mean time since diagnosis of Tourette syndrome was 3.3 years. The mean baseline YGTSS-TTS was 33.8 points.

Results showed the difference in YGTSS-TTS was not significant between the high-dose deutetrabenazine and placebo groups (least-squares mean difference, –0.8 points; 95% CI, –3.9 to 2.3 points at 8 weeks). The key secondary endpoints were not nominally significantly different between groups.

Coffey and colleagues reported 34 patients treated with high-dose deutetrabenazine, 24 (44%) treated with low-dose deutetrabenazine and 25 (49%) treated with placebo had TEAEs that were generally mild or moderate.

In a related editorial, Mark S. Baron, MD, from Virginia Commonwealth University Parkinson’s Movement Disorders Center, said the study along with other large controlled clinical trials do not suggest effectiveness of vesicular monoamine transporter 2 (VMAT-2) inhibitors like deutetrabenazine for the treatment of tics in patients with Tourette syndrome. Coffey and colleagues found improvement in YGTSS-TTS favoring deutetrabenazine compared with placebo at the end of the 4-week titration; however, this demonstrates a placebo effect.

“Considering the frequency of TEAEs, a high proportion of the participants who were treated with a VMAT-2 drug were surely unblinded to the fact that they were receiving a drug and not a placebo; therefore, they would have been more likely to have perceived a benefit early on,” Baron wrote. “The lack of benefits in primary and secondary measures at 8 weeks should support this impression.”