A Cost-Effectiveness Model of Semaglutide 2.4 mg, Resmetirom 80 mg, and Resmetirom 100 mg Versus Standard of Care for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis in the United States.

backgroundGiven the considerable clinical and economic burden posed by non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced fibrosis, there is a substantial demand for effective treatment options. Although semaglutide 2.4 mg has demonstrated clinical benefits in this patient population and offers a promising new treatment option, it is also essential for payers to understand the financial impact. This study used a cohort Markov state-transition cost-effectiveness model to evaluate the cost effectiveness of semaglutide 2.4 mg and resmetirom (80 mg and 100 mg), with each treatment compared against standard of care (SoC) in patients with non-cirrhotic MASH with moderate to advanced fibrosis.

methodsCost effectiveness was assessed from a United States (US) third-party payer perspective. The impact of semaglutide 2.4 mg on quality-adjusted life years (QALYs), cost, and clinical outcomes was simulated over a lifetime horizon. Mortality rates, treatment discontinuation, and disease transition probabilities were based on published literature and clinical trials (i.e., ESSENCE, MAESTRO-NASH). Costs were adjusted to 2025 US dollars. Costs and health outcomes were discounted at 3% annually. Cost effectiveness was evaluated at willingness-to-pay (WTP) thresholds of $50,000, $100,000, and $150,000 per QALY gained. Sensitivity, subgroup, and scenario analyses were performed by varying model parameters.

resultsIn the base case analysis, treatment with semaglutide 2.4 mg produced an additional 1.66 QALYs with an incremental cost of US$33,031 compared with SoC. Treatment with resmetirom 80 mg and resmetirom 100 mg produced an additional 1.20 and 1.24 QALYs with incremental costs of US$415,110 and US$245,991, respectively, compared with SoC. In the cost-effectiveness analysis, semaglutide 2.4 mg had an incremental cost-effectiveness ratio of US$19,911 per QALY gained compared with SoC, while corresponding incremental cost-effectiveness ratios were US$346,810 for resmetirom 80 mg and US$198,607 for resmetirom 100 mg. At a WTP threshold of US$150,000, semaglutide 2.4 mg was cost effective in 99.5% of simulations. Sensitivity analyses confirmed the robustness of these findings. In a scenario analysis that used the direct-to-consumer cash price for semaglutide 2.4 mg (US$499 per month), semaglutide 2.4 mg was less costly and more effective than SoC.

conclusionOur model indicates that semaglutide 2.4 mg is clinically favorable and cost effective compared with SoC, while demonstrating more favorable economic outcomes than resmetirom, for patients with non-cirrhotic MASH with moderate to advanced fibrosis. Notably, semaglutide 2.4 mg demonstrates a cost per QALY gain that is significantly lower than commonly accepted WTP thresholds. Overall, our findings suggest that semaglutide 2.4 mg represents an economically viable option for US payers.