Safety Profile of Resmetirom: A Real-World Study Based on FAERS Database

Objective: To systematically evaluate adverse event reporting patterns and potential safety signals associated with resmetirom using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: FAERS reports from the first quarter of 2024 through the second quarter of 2026 were analyzed. Adverse events associated with resmetirom were coded using the Medical Dictionary for Regulatory Activities and evaluated at the Preferred Term (PT) and System Organ Class (SOC) levels. Signal detection was performed using the reporting odds ratio, proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Multi-item Gamma Poisson Shrinker. A signal was considered positive only when all 4 algorithms met their predefined criteria. Time-to-onset patterns were further assessed using Weibull distribution analysis. Results: A total of 2035 resmetirom-related reports were identified. The most frequently reported adverse events included diarrhea, nausea, pruritus, fatigue, and increased alanine aminotransferase. Positive PT-level signals were observed across gastrointestinal, hepatobiliary, laboratory, and thyroid-related events, including diarrhea, nausea, abdominal pain, hepatotoxicity, suspected drug-induced liver injury, cholelithiasis, and abnormalities in thyroid function tests. At the SOC level, investigations and hepatobiliary disorders met all 4 signal detection criteria. Among 220 reports with valid onset information, the median time to onset was 14.5 days (interquartile range, 1.5-60.5 days). The Weibull shape parameter was 0.60 (95% CI, 0.54-0.67), indicating an early failure pattern. Conclusions: This postmarketing pharmacovigilance study largely reinforced the known gastrointestinal, hepatic, gallbladder, and thyroid-related safety profile of resmetirom while identifying additional reporting signals that warrant further investigation. Adverse events tended to be reported early after treatment initiation, supporting closer monitoring during the initial treatment period. These findings should be interpreted as disproportionality signals rather than evidence of incidence or causality and require validation in longitudinal real-world studies.