Real-world pharmacovigilance analysis and cross-database consistency assessment of resmetirom-related adverse events using FAERS and VigiAccess

Abstract

Objective This study aimed to characterize the post-marketing safety profile and potential adverse event signals of resmetirom using the FAERS and VigiAccess databases. Methods FAERS reports from the quarter of initial United States approval through 2026Q1 were analyzed. After deduplication, DEMO, DRUG, REAC, THER, and OUTC tables were integrated, and reports listing resmetirom as the primary suspect drug were included. Disproportionality analysis used four methods: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), with IC and EBGM as the respective Bayesian signal metrics. PTs meeting all four predefined criteria were defined as robust signals. Additional analyses assessed SOC/PT profiles, label expectedness, seriousness and outcomes, time-to-onset (TTO), Weibull patterns, and cross-database consistency with VigiAccess. Results We identified 1,409 resmetirom-related FAERS reports and 1,417 VigiAccess reports. Sixty-two robust PT signals across nine SOCs were detected, mainly involving gastrointestinal disorders, investigations, hepatobiliary disorders, and skin and subcutaneous tissue disorders. Prominent signals included diarrhoea, nausea, pruritus, alanine aminotransferase increased, aspartate aminotransferase increased, abdominal pain upper, dizziness, vomiting, weight decreased, and hepatic cirrhosis. Among FAERS reports, 419 (29.7%) were serious and 65 (4.6%) reported death. Sixteen robust PTs were not listed as corresponding adverse reactions in either the current United States. Prescribing Information or European SmPC. Complete temporal information was available for 170 reports (12.1%); median TTO was 26 days (IQR, 5–66), and the Weibull shape parameter was 0.72 (95% CI, 0.64–0.80), indicating an early-failure pattern. SOC-stratified analyses showed heterogeneous onset patterns. FAERS and VigiAccess showed high descriptive concordance in SOC- and PT-level reporting patterns (Spearman ρ = 0.998). Conclusion Resmetirom-related reports were mainly gastrointestinal, laboratory, hepatobiliary, and skin-related. Hepatobiliary signals warrant particular attention, while cross-database concordance provides supportive, non-causal pharmacovigilance evidence.