OBJECTIVES: Lipid levels impact cardiovascular disease (CVD) risk, including stroke and myocardial infarction. This analysis assessed the impact of treatment-related changes in lipid levels resulting from two potential treatments for nonalcoholic steatohepatitis (NASH), resmetirom and obeticholic acid (OCA), on costs and health outcomes versus placebo from a U.S. healthcare payer perspective over a lifetime horizon.

METHODS: Using Monte Carlo simulation, a scenario analysis was performed in a previously conducted cost-effectiveness analysis comparing resmetirom, OCA, and placebo. It was assumed that the active treatments would have identical fibrosis outcomes as estimated in the placebo arm, with changes in lipid levels, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides, being the only parameters explored to assess impact on overall cost-effectiveness. Based on published evidence, the change in lipid levels versus placebo was estimated for resmetirom (HDL: +3.80%; LDL: -17.30%; triglycerides: -36.00%) and OCA (HDL: -8.67%; LDL: +15.07%; triglycerides: -21.64%). CVD risk was assessed based on the Framingham risk calculator.

RESULTS: The lifetime CVD event risks for resmetirom, OCA, and placebo were 46.67%, 61.97%, and 60.28%, respectively. The lifetime CVD-associated mortality rates were estimated at 10.91%, 14.48%, and 14.09%, respectively. Over a lifetime horizon, changes in CVD events led to a quality-adjusted life-year (QALY) gain of 0.152 for resmetirom and a QALY loss of 0.135 for OCA versus placebo. Additionally, per patient costs of CVD events were decreased by $5,785 with resmetirom and increased by $719 with OCA. Net monetary benefits of $21,029 and -$14,264 for CVD events were estimated for resmetirom and OCA, respectively.

CONCLUSIONS: Changes in CVD event risk factors are strong drivers of cost-effectiveness in economic evaluations of treatments for NASH. Therapies that reduce lipid levels may enhance the effect of fibrosis improvement and lead to improved quality-of-life and reduced costs among patients with NASH.