Early post-marketing safety profile of resmetirom in FAERS: an exploratory assessment of statin co-reporting.

BACKGROUND

Resmetirom is the first thyroid hormone receptor-beta agonist approved in the United States for adults with non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) and moderate-to-advanced fibrosis. Dyslipidemia and cardiovascular risk are common in MASH, making statin co-use clinically relevant.

AIM: This study aims to characterize early post-marketing adverse event reporting for resmetirom in the FDA Adverse Event Reporting System (FAERS) and explore resmetirom-statin co-reporting.

METHODS

Cleaned and deduplicated FAERS reports from 2024 Q1 to 2026 Q1 were analyzed. Positive preferred-term (PT) signals required at least three reports and concordant positivity for the reporting odds ratio, proportional reporting ratio, and Bayesian information component. Reporter-type sensitivity analysis was restricted to healthcare professional (HCP) reports. Exploratory resmetirom-statin analyses used a suspect-anchored definition and prespecified hepatic, gallbladder-related, and muscle-related outcomes.

RESULTS

Among 3,155,054 unique FAERS cases, 1,407 were included in the resmetirom single-drug analysis and 267 met the primary resmetirom-statin co-reporting definition. Reports were concentrated in gastrointestinal, hepatobiliary, investigation, and skin-related system organ classes. The leading positive PTs were diarrhea, nausea, pruritus, alanine aminotransferase increased, and aspartate aminotransferase increased. The findings were compatible with the FDA label and remained similar in the reporter-type sensitivity analysis. Unlabeled terms among the top 20 signals included weight decreased and abdominal discomfort, which require cautious interpretation. Exploratory DDI analysis did not identify a consistent interaction-specific signal for the prespecified hepatic, gallbladder-related, or muscle-related outcomes. Rhabdomyolysis/myopathy was based on five co-reports; the odds ratio was elevated, whereas Omega025 was negative.

CONCLUSION

Early FAERS data indicate a resmetirom reporting spectrum mainly concordant with the FDA label. Unlabeled non-specific PTs, including weight decreased and abdominal discomfort, require cautious interpretation. Resmetirom-statin co-reporting did not show a stable interaction signal.