Comprehensive Safety Evaluation of Valbenazine in Tardive Dyskinesia: A Meta-Analysis of Randomized Controlled Trials and Disproportionality Analysis of FAERS
Author(s)
Muhammed F. KT1, Beema T. Yoosuf, PhD2, aparna ashok bhosale, M pharm2, Mamidi Niveditha, MS, PhD2, Dipika Bansal, MD2.
1PhD Research Scholar, National Institute of Pharmaceutical Education and Research, Mohali, India, 2National Institute of Pharmaceutical Education and Research - NIPER, S.A.S. Nagar,, Mohali, India.
1PhD Research Scholar, National Institute of Pharmaceutical Education and Research, Mohali, India, 2National Institute of Pharmaceutical Education and Research - NIPER, S.A.S. Nagar,, Mohali, India.
OBJECTIVES: Concerns about the long-term safety of valbenazine persist, particularly due to limited evidence on rare or delayed adverse events (AEs). This study integrates safety data on valbenazine for the treatment of tardive dyskinesia (TD) from randomized controlled trials (RCTs) and the FDA Adverse Event Reporting System (FAERS).
METHODS: Comprehensive searches were conducted in PubMed, EMBASE, Ovid-MEDLINE, and ClinicalTrials.gov to identify RCTs evaluating the safety of valbenazine in patients with TD. A random-effects meta-analysis was performed to calculate Peto odds ratios (OR) with 95% confidence intervals (CIs). Additionally, the FAERS database was queried using OpenVigil 2.1. Disproportionality analysis was conducted using the Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR), with signal refinement achieved by restricting the drug role to “primary suspect.”
RESULTS: Nine RCTs were included. Valbenazine use was significantly associated with an increased risk of somnolence (OR = 3.42; 95% CI: 1.97-5.92; p < 0.01) and akathisia (OR = 2.85; 95% CI: 1.03-7.89; p = 0.04). Higher odds were observed for dry mouth (OR = 15.51; 95% CI: 0.19-11.9), fatigue (OR = 2.27; 95% CI: 0.93-5.59), dyskinesia (OR = 3.56; 95% CI: 0.93-13.67), and salivary hypersecretion (OR = 1.71; 95% CI: 0.53-5.50). Additionally, valbenazine was not associated with an increased risk of dizziness or headache. In the FAERS database, 14,873 patients were reported to have experienced AEs associated with valbenazine. Among the Preferred Terms (PTs), somnolence was the most frequently reported event (n = 1347), demonstrating a strong signal with a PRR of 10.36 and an ROR of 10.67. Dyskinesia, reported in 493 cases, also exhibited a notable signal with a PRR of 18.83 and an ROR of 17.76.
CONCLUSIONS: This study identified several labeled and unlabeled AEs linked to valbenazine, highlighting the need for continued monitoring to support informed, risk-benefit-based clinical decisions.
METHODS: Comprehensive searches were conducted in PubMed, EMBASE, Ovid-MEDLINE, and ClinicalTrials.gov to identify RCTs evaluating the safety of valbenazine in patients with TD. A random-effects meta-analysis was performed to calculate Peto odds ratios (OR) with 95% confidence intervals (CIs). Additionally, the FAERS database was queried using OpenVigil 2.1. Disproportionality analysis was conducted using the Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR), with signal refinement achieved by restricting the drug role to “primary suspect.”
RESULTS: Nine RCTs were included. Valbenazine use was significantly associated with an increased risk of somnolence (OR = 3.42; 95% CI: 1.97-5.92; p < 0.01) and akathisia (OR = 2.85; 95% CI: 1.03-7.89; p = 0.04). Higher odds were observed for dry mouth (OR = 15.51; 95% CI: 0.19-11.9), fatigue (OR = 2.27; 95% CI: 0.93-5.59), dyskinesia (OR = 3.56; 95% CI: 0.93-13.67), and salivary hypersecretion (OR = 1.71; 95% CI: 0.53-5.50). Additionally, valbenazine was not associated with an increased risk of dizziness or headache. In the FAERS database, 14,873 patients were reported to have experienced AEs associated with valbenazine. Among the Preferred Terms (PTs), somnolence was the most frequently reported event (n = 1347), demonstrating a strong signal with a PRR of 10.36 and an ROR of 10.67. Dyskinesia, reported in 493 cases, also exhibited a notable signal with a PRR of 18.83 and an ROR of 17.76.
CONCLUSIONS: This study identified several labeled and unlabeled AEs linked to valbenazine, highlighting the need for continued monitoring to support informed, risk-benefit-based clinical decisions.
Conference/Value in Health Info
2025-09, ISPOR Real-World Evidence Summit 2025, Tokyo, Japan
Value in Health Regional, Volume 49S (September 2025)
Code
RWD152
Topic Subcategory
Reproducibility & Replicability
Disease
SDC: Neurological Disorders