(SLA-056) Neurological Adverse Events Associated with Valbenazine in Tardive Dyskinesia: A Meta-Analysis of Randomized Controlled Trials and FAERS Based Disproportionality Analysis

Background: Valbenazine is a commonly used drug for tardive dyskinesia (TD), but limited evidence on rare and delayed neurological adverse events (AEs) raises ongoing concerns about its safety profile.

Objectives: To evaluate the risk of neurological AEs in patients with TD treated with valbenazine, utilizing data from randomized controlled trials (RCTs) and the FDA Adverse Event Reporting System (FAERS).

Methods: We conducted comprehensive searches on PubMed, EMBASE, Ovid MEDLINE, and ClinicalTrials.gov to identify RCTs assessing the safety of valbenazine in patients with TD till September 2024. The primary outcome is to assess the risk associated with valbenazine use and the occurrence of all neurological AEs. A random-effects meta-analysis was performed to calculate the Peto odds ratio (OR) with 95% confidence intervals (CIs). Additionally, the quality of the findings was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. The FAERS database was queried using Open Vigil 2.1 until September 2024. Disproportionality was assessed using the proportional reporting ratio (PRR) and reporting odds ratio (ROR), with signal refinement performed by restricting the drug roles to primary suspect.

Results: For the safety meta-analysis, nine RCTs with available AEs were examined. A total of 153 AEs were found associated with the valbenazine group and 52 AEs with placebo. Valbenazine significantly increased the risk of somnolence (OR=3.42, 95% CI: 1.97-5.92, p: < 0.0001) and akathisia (OR, 2.85 [95% CI: 1.03-7.89], p: 0.0435) compared with the placebo. The GRADE approach rated the evidence as low. In the FAERS database, 14,873 patients were reported with AEs associated with valbenazine. Disproportionality analysis identified 20 neurological AEs strongly associated with valbenazine, with signal refinement confirming these associations. Notable AEs include parkinsonism (ROR=53.84, PRR=58.46), somnolence (ROR =10.67, PRR=10.67), tremor (ROR =7.89, PRR=8.03), dyskinesia (ROR =17.76, PRR=18.83), drooling (ROR =117.26, PRR=125.30), and balance disorders.

Conclusions: This study identified both known and novel neurological AEs associated with valbenazine, emphasizing the need for further investigation. These findings support clinicians in optimizing risk-benefit assessments for safer therapeutic use.