Custo-Efetividade do Resmetirom para Esteato-Hepatite associada a disfunção metabólica no Brasil

Abstract

Introduction: Metabolic dysfunctionassociated steatohepatitis (MASH) is a chronic, progressive liver disease characterized by steatosis, lobular inflammation, and hepatocellular ballooning, which may progress to advanced fibrosis and cirrhosis. MASH is estimated to affect 5.3% of the global adult population. Recently, resmetirom, the first drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of MASH with fibrosis, demonstrated promising clinical results. Objective: To evaluate the costeffectiveness of resmetirom compared with placebo for the treatment of metabolic dysfunctionassociated steatohepatitis (MASH) with liver fibrosis in Brazil. Methods: A Markov model with a 20year time horizon and annual cycles was developed using TreeAge Pro 2009. Resmetirom was compared with standard care from the healthcare system perspective. The hypothetical cohort included patients with MASH at fibrosis stages F0 to F4. Patients were eligible to receive resmetirom if they were at fibrosis stages F2–F3. Healthstate transitions, clinical event probabilities, and effectiveness data were obtained from international studies. Direct costs were estimated using Brazilian data sources and adjusted to 2024 purchasing power parity (PPP) US dollars. Outcomes were expressed as qualityadjusted life years (QALYs). An annual discount rate of 5% was applied to both costs and outcomes. Oneway deterministic and probabilistic sensitivity analyses with 1,000 simulations were performed. Results: The resmetirom strategy resulted in an accumulated cost of US$263,157 and an effectiveness of 6.94 QALYs, compared with US$143,033 and 5.86 QALYs for standard care. The incremental costeffectiveness ratio (ICER) was US$111,252 per QALY gained, exceeding the costeffectiveness thresholds commonly adopted in Brazil and internationally. In the deterministic sensitivity analysis, the parameters with the greatest influence on the ICER were the cost of resmetirom, the discount rate, and the treatmentrelated risk difference. The probabilistic sensitivity analysis demonstrated robust findings, with resmetirom consistently being more costly and more effective. The ICER distribution ranged from PPPUS$53,279 to PPPUS$209,016 per QALY, with a median of PPPUS$122,951 per QALY. Conclusions: Resmetirom provides incremental clinical benefit in the management of MASH with F2–F3 fibrosis; however, its incremental costeffectiveness ratio exceeds the thresholds generally considered acceptable in Brazil. A price reduction would be necessary for its incorporation into the Brazilian healthcare system to be considered economically feasible.