S2923 Resmetirom Significantly Reduces Mortality and Complications in MASLD: A Matched Cohort Study

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern with limited pharmacologic options. Resmetirom, a selective thyroid hormone receptor-β (THR-β) agonist, has demonstrated promise in improving hepatic steatosis and metabolic parameters in early-phase studies. However, real-world data on clinical outcomes remain limited. This study aimed to evaluate the association between resmetirom use and major clinical outcomes in patients with MASLD using a large, real-world dataset. Methods: Using the TriNetX research network, we identified adult patients with MASLD were identified via International Classification of Diseases, Tenth Revision (ICD-10) codes. Resmetirom exposure was defined as documented use after MASLD diagnosis. A 1:1 propensity score matching was performed based on demographics, cirrhosis status, metabolic comorbidities, and baseline laboratory values. Patients with pre-existing outcomes were excluded prior to follow-up (mean follow-up is 135 days). Primary outcomes included all-cause mortality, hepatic complications (ascites, spontaneous bacterial peritonitis [SBP], variceal bleeding, portal hypertension), cardiovascular events, renal outcomes (dialysis initiation, CKD progression), healthcare utilization (hospitalizations, outpatient visits), and secondary malignancies. Time-to-event analyses were conducted using Kaplan-Meier curves and Cox proportional hazards models. Results: Among 2,380 matched patients (1,190 patients in the resmetirom group and 1,190 matched controls), resmetirom use was associated with significantly lower all-cause mortality (0.8% vs 2.1%, HR 0.16, P = 0.010). Cardiovascular events, including cardiac arrest and myocardial infarction, occurred only in controls (0.8% and 0.9%, respectively; P < 0.01). Hepatic decompensation events were less frequent in the resmetirom group, with hazard ratios ranging from 0.25 to 0.36 (P < 0.05). Hospitalizations (1.1% vs 3.6%, HR 0.31, P < 0.001) and dialysis initiation (0.9% vs 0%, P = 0.001) were also significantly reduced. Despite a higher numerical rate of cirrhosis progression (4.7% vs 2.3%), time-to-event analysis favored the control group (HR 4.5, P = 0.001). Secondary malignancies and liver transplantation occurred only in controls. Conclusion: Resmetirom use in MASLD patients was associated with improved clinical outcomes, including reduced mortality, hepatic and cardiovascular complications, and healthcare utilization. These findings support further prospective evaluation of resmetirom in MASLD treatment.