OBJECTIVES: Valbenazine (VBZ) and deutetrabenazine (DTBZ) are approved for treating tardive dyskinesia (TD) in adults, but no head-to-head studies of these medications have been conducted. This analysis assessed the relative efficacy of VBZ and DTBZ, using an indirect treatment comparison (ITC) of data from double-blind, placebo-controlled studies.

METHODS: The analysis included four studies: two 6-week VBZ trials (KINECT2 [25-75mg]; KINECT3 [40 or 80mg]) and two 12-week DTBZ trials (ARM-TD [12-48mg]; AIM-TD [12, 24, or 36mg]). Trials were pooled (KINECT2/KINECT3; ARM-TD/AIM-TD) using Cochrane’s Revman 5.3. Analyses included the mean change from baseline (CFB) in the Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1-7) and an AIMS response threshold (≥50% total score improvement from baseline). For AIMS CFB, the Bucher ITC method was used to compare pooled VBZ (25-80mg, 6 weeks) with pooled DTBZ (12-48mg, 6/8 weeks [data extracted from publications using a plot digitizer]). Since DTBZ 12mg did not demonstrate efficacy in AIM-TD, a more conservative analysis was conducted that excluded this dose from the pooled DTBZ dataset. For AIMS response, an ITC of pooled VBZ (25-80mg, 6 weeks) was compared with pooled DTBZ (12-48mg, 12 weeks [no available visual data for 6/8 week]).

RESULTS: For AIMS CFB, the ITC statistically favored pooled VBZ (n=178, placebo n=89) versus pooled DTBZ (n=222, placebo n=117) (mean difference [95% CI], -1.39 [-2.39, -0.39];P<0.01). VBZ was also statistically favored when DTBZ 12mg was removed (mean difference [95% CI], -1.17 [-2.19, -0.15];P<0.05). For AIMS response, the ITC favored pooled VBZ versus pooled DTBZ with an odds ratio (95% CI) of 2.30 (0.91, 5.81).

CONCLUSIONS: Results of this ITC suggest that VBZ had statistically stronger efficacy in treating TD than DTBZ. Methodological and other study factors such as inclusion criteria, concomitant medications, and TD severity may need to be considered when interpreting the results.