Translating Trial to Treatment: A Scoping Review of Resmetirom First Year in Real-World Use for Moderate to Advanced...

Metabolic dysfunction-associated steatohepatitis (MASH), formally known as nonalcoholic steatohepatitis (NASH), a progressive subtype of nonalcoholic fatty liver disease (NAFLD), remains a major global contributor to liver-related morbidity and mortality. In early 2024, a new therapeutic option, Resmetirom, a liver-directed thyroid hormone receptor beta (THR-β) agonist, became available in the United States for individuals with MASH having moderate to advanced liver fibrosis (F2-F3), offering a targeted approach to treatment. This review aims to explore and consolidate real-world experience, clinical insights, regulatory developments, and implementation practices related to the use of Resmetirom within its first year of availability. This scoping review was conducted using a structured methodology aligned with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) guidelines. Relevant literature was identified through systematic searches in PubMed, Google Scholar, and clinical trial registries, using Boolean operators (AND). Search specificity was tested during strategy development, and studies published between April 2024 and May 2025 were included based on PICOS (Population, Intervention, Comparison, Outcomes, and Study Designs) criteria, focusing on adults with noncirrhotic MASH and F2-F3 fibrosis treated with Resmetirom. Study designs included clinical trials, observational studies, post-market reports, and real-world evidence. Supplementary data were extracted from Food and Drug Administration (FDA) and European Medicines Agency (EMA) announcements and proceedings from major liver congresses - American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL). The findings from the 20 studies included in this review were described using a narrative approach and grouped according to key themes. Key clinical trials and real-world data from the United States show that Resmetirom is effective in treating MASH, lowering liver fat and improving liver scarring in patients with moderate to advanced fibrosis (F2-F3). It also appears to be safe and well-tolerated, with good early adherence. Noninvasive tests to diagnose and monitor the disease are being used more often, but relying mainly on FIB-4 might miss some advanced cases. However, access to Resmetirom remains a challenge due to its high cost, insurance barriers, and limited evidence from global or high-risk populations. These issues highlight the need for fairer access and more post-approval studies to ensure broader use and understanding of the drug. In its first year of post-approval use, Resmetirom has shown consistent efficacy, safety, and quality-of-life benefits for patients with MASH and fibrosis. However, real-world adoption remains limited by high costs, complex access pathways, underrepresentation of high-risk populations, and a lack of global data. This review highlights existing evidence gaps and stresses the importance of global validation, improved diagnostic tools, and fair access to ensure Resmetirom can achieve its full clinical potential.