OBJECTIVES: Resmetirom is an orally-administered, liver-targeted, thyroid hormone receptor-beta selective agonist which has shown promising results in Phase 2/3 trials for nonalcoholic steatohepatitis (NASH). A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to assess the efficacy of resmetirom compared with obeticholic acid (OCA) and placebo. An economic evaluation was subsequently performed to explore the cost-effectiveness of resmetirom versus OCA and placebo from a US healthcare payer perspective.

METHODS: A comprehensive search of key databases was conducted through 05 May 2022 to identify eligible randomized controlled trials (RCTs). An NMA within the Bayesian framework was performed to assess the comparative efficacy of resmetirom versus OCA and placebo on outcomes (NASH resolution, fibrosis improvement, fibrosis stabilization, fibrosis at least stable, fibrosis worsening). To explore cost-effectiveness, a Markov model was developed to simulate the course of NASH over a lifetime horizon. A willingness-to-pay threshold of $100,000 was applied to assess cost-effectiveness.

RESULTS: Overall, 64 publications were included in the SLR. In the NMA, 5 interventions within 5 trials (with 1,579 participants) were compared. For the outcome of fibrosis improvement, resmetirom was superior to OCA and placebo (posterior probability of success = 58% and 68%, respectively). Resmetirom was also superior to OCA and placebo for the fibrosis at least stable outcome. For the other outcomes, resmetirom was similar to OCA but superior to placebo. The Markov model indicated resmetirom had a higher probability of being cost-effective versus placebo (incremental cost-effectiveness ratio = $74,018) and was dominant versus OCA (less costly and more effective).

CONCLUSIONS: In an SLR and NMA including eligible RCTs, resmetirom was superior to OCA and placebo for the outcomes of fibrosis improvement and fibrosis at least stable. Furthermore, an economic evaluation showed resmetirom would be cost-effective for treatment of NASH; improving clinical outcomes and reducing costs.