Valbenazine Improves Tardive Dyskinesia With or Without Concomitant Antipsychotic Therapy: A Meta-Analysis of Three Long-Term Valbenazine Trials

Abstract: Background: Valbenazine is a highly selective vesicular monoamine transporter 2 inhibitor indicated for tardive dyskinesia (TD), a persistent and potentially debilitating movement disorder associated with prolonged antipsychotic exposure. Given the paucity of data regarding the course of TD in patients no longer taking antipsychotics, a meta-analysis of 3 long-term valbenazine studies was conducted in subgroups with and without concomitant antipsychotic use at baseline. Methods: KINECT™-3 (NCT02274558), KINECT™-4 (NCT02405091), and J KINECT (NCT03176771) data were analyzed in study completers taking antipsychotics at baseline (AP+) and those who were not (AP-). The Abnormal Involuntary Movement Scale (AIMS) total score was used to measure TD severity at baseline, Wk48 (end of valbenazine treatment), and Wk52 (4 weeks after valbenazine withdrawal). The meta-analysis implemented a random-effects model that weighted each study based on inverse variance, adjusted for between-study variance. Results: Of 576 enrolled patients, 336 (58.3%) were study completers and included for analysis: AP+ (n=269); AP- (n=67). Mean baseline AIMS scores ranged from 7.9–14.9 (AP+) and 10.9–14.5 (AP-). Mean changes from baseline in AIMS scores indicated substantial TD improvements with valbenazine at Wk48 (AP+, 6.1; AP-, -6.5) and return towards baseline severity at Wk52 (AP+, -2.1; AP-, -1.4). Conclusions: Once-daily valbenazine treatment resulted in substantial and sustained TD improvement through Wk48, with no meaningful differences between AP+ and AP- subgroups. The return towards baseline severity after valbenazine withdrawal shows TD is chronic and often irreversible, even in patients no longer taking antipsychotics. Continuous treatment with valbenazine may be warranted irrespective of antipsychotic therapy.Short Description: Valbenazine is indicated for once-daily treatment of tardive dyskinesia (TD), a movement disorder associated with prolonged antipsychotic exposure. Data from 3 long-term studies (KINECT™-3, KINECT™-4, J-KINECT) were analyzed to assess effects of valbenazine on TD severity in patients with or without concomitant antipsychotic use at baseline. Substantial and sustained TD improvement was observed through 48 weeks of valbenazine treatment, regardless of baseline antipsychotic use. After valbenazine withdrawal, TD severity returned towards baseline in both subgroups.Name of Sponsoring Organization(s): This study was funded by Neurocrine Biosciences, Inc.