Tirzepatide and Semaglutide Cost-Effective for MASH with F2-F3 Fibrosis, Resmetirom Not
Background
Metabolic dysfunction-associated steatohepatitis (MASH), characterized by inflammation and liver damage, is a severe progression of MASLD and a leading cause of advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Despite its high prevalence, effective pharmacological therapies for MASH with significant fibrosis (F2-F3) remain limited, often relying on lifestyle modifications. The recent emergence of new pharmacotherapies, such as resmetirom, semaglutide, and tirzepatide, necessitates a robust value assessment to guide U.S. healthcare payer decisions and ensure equitable patient access. This study addresses the critical gap in understanding the cost-effectiveness of these novel treatments.
Study Design
Researchers developed a Markov cohort model to evaluate the cost-effectiveness of pharmacotherapies for U.S. adults with MASH and F2-F3 fibrosis, adopting a lifetime horizon from a U.S. healthcare payer perspective. The model simulated biopsy-confirmed patients progressing through liver-specific health states. Efficacy inputs for fibrosis regression and MASH resolution were derived from a Bayesian network meta-analysis. Each pharmacotherapy (resmetirom, semaglutide, tirzepatide) was individually compared against standard of care. Cost-effectiveness was assessed using a $100,000/QALY willingness-to-pay threshold.
Results
In the base-case analysis, tirzepatide demonstrated the largest Quality-Adjusted Life-Year (QALY) gain and the lowest incremental cost compared to standard of care. > Tirzepatide yielded an incremental cost-effectiveness ratio (ICER) of ($42,705/QALY), indicating high value. Semaglutide was also found to be cost-effective, with an ICER of $80,076/QALY. In contrast, resmetirom's ICER of $273,445/QALY significantly exceeded the $100,000/QALY willingness-to-pay threshold, suggesting it is not cost-effective at current U.S. prices. Sensitivity analyses revealed that drug price was the most influential parameter. Probabilistic sensitivity analysis further supported these findings, showing a 99.5% probability of cost-effectiveness for tirzepatide and 89.8% for semaglutide at the $100,000/QALY threshold. These results highlight substantial differences in the economic value proposition of these emerging MASH therapies.
Why It Matters
This economic analysis provides crucial insights for U.S. healthcare payers and clinicians navigating the landscape of emerging MASH therapies. Understanding the cost-effectiveness of resmetirom, semaglutide, and tirzepatide is vital for formulary decisions and ensuring equitable patient access. The findings suggest that GLP-1/GIP receptor agonists, specifically tirzepatide and semaglutide, offer a cost-effective long-term solution for patients with MASH and significant fibrosis, potentially reducing the burden of disease progression over a lifetime. While resmetirom is FDA-approved for MASH, its current pricing renders it less cost-effective in this model. This underscores the need for value-based pricing strategies to align drug costs with their clinical benefits and societal value, particularly as more therapies become available for this prevalent and progressive liver disease.