Cost‐Effectiveness of Pharmacologic Therapies for Metabolic Dysfunction–Associated Steatohepatitis With Significant Fibrosis in the United States

AIMS: The approval of new pharmacotherapies for metabolic dysfunction-associated steatohepatitis (MASH) presents a critical need for value assessment. We evaluated the cost-effectiveness of resmetirom, semaglutide and tirzepatide for U.S. adults with MASH and F2-F3 fibrosis. MATERIALS AND METHODS: We developed a Markov cohort model with a lifetime horizon from the perspective of a U.S. healthcare payer. The model simulated biopsy-confirmed patients with MASH progressing through liver-specific health states. Efficacy inputs for fibrosis regression and MASH resolution were obtained from a Bayesian network meta-analysis. Each pharmacotherapy was compared individually against standard of care; a formal sequential incremental analysis across active therapies was not performed. Cost-effectiveness was assessed against the standard of care using a $100 000/QALY willingness-to-pay threshold. RESULTS: In the base-case analysis, tirzepatide had the largest QALY gain and the lowest incremental cost relative to standard of care, yielding an incremental cost-effectiveness ratio of ($42 705/QALY). Semaglutide was also cost-effective (ICER: $80 076/QALY). Resmetirom (ICER: $273 445/QALY) exceeded the WTP threshold. Drug price was the most influential parameter in sensitivity analyses; probabilistic sensitivity analysis showed a 99.5% probability of cost-effectiveness for tirzepatide and 89.8% for semaglutide at $100 000/QALY. CONCLUSIONS: At current U.S. prices, tirzepatide and semaglutide are cost-effective for MASH with F2-F3 fibrosis, while resmetirom is not. The tirzepatide finding should be interpreted with caution, given that it is not yet FDA-approved for MASH and its effect estimate is based on a network meta-analysis of a phase 2 trial. Payer coverage and equitable access to MASH therapies require value-based pricing strategies.