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

Introduction 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 TM -3 (NCT02274558), KINECT TM -4 (NCT02405091), and JKINECT (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. Funding Neurocrine Biosciences, Inc.