OBJECTIVES: Resmetirom is an oral, liver-directed, thyroid hormone receptor beta (THR-β) selective agonist in Phase III development for nonalcoholic steatohepatitis with significant fibrosis (NASH). An economic evaluation was conducted to assess the cost-effectiveness of resmetirom in the US setting.

METHODS: A Markov model was developed consisting of two sub-models of NASH, with and without cardiovascular (CV) history. In each sub-model, patients transitioned among no-fibrosis (F0) and fibrosis (F1-F3) stages, compensated cirrhosis (or F4), decompensated cirrhosis, hepatocellular carcinoma, post-liver transplant, and death. Data from a published randomized clinical trial of resmetirom versus placebo were used to populate the model. The transition from the first to second sub-model was driven by the first occurrence of a nonfatal CV event in NASH patients, estimated based on pooled baseline patient characteristics. The model captured worsening and improvement in the patients’ fibrosis stages (F0-F3) based on changes in liver fat, as assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF). Model outcomes were quality-adjusted life-years (QALYs), cirrhosis/F4 and liver transplant cases avoided, and costs. Deterministic and probabilistic sensitivity analyses (DSA/PSA) were performed, with a willingness-to-pay threshold of $100,000/QALY applied.

RESULTS: An incremental 1.392 QALYs were gained in the resmetirom arm, with an incremental cost of $107,705 compared to no-treatment. The incremental cost/QALY gained for resmetirom versus no-treatment was $77,348. The cirrhosis/F4 and liver transplant risks were reduced by 32.48% and 33.82%, leading to cost savings of $47,880 (-39.98%) and $32,372 (-40.50%) in the resmetirom arm, respectively. The most impactful input parameter was the proportion of patients achieving fibrosis improvement in both arms, according to DSA. The PSA showed that resmetirom was cost-effective, with a probability of 70%.

CONCLUSIONS: Model results showed that managing NASH with resmetirom would be cost-effective in the US; reducing or preventing end-stage liver events and associated costs.