Efficacy and safety of resmetirom for the treatment of nonalcoholic steatohepatitis: a GRADE assessed systematic review and meta-analysis

Abstract

There are no Food and Drug Administration (FDA)-approved treatment options for nonalcoholic steatohepatitis (NASH) which is a prevailing disease that leads to fibrosis, cirrhosis, or hepatocellular carcinoma. Hence, this systematic review and metaanalysis aims to determine the efficacy and safety of resmetirom, the first FDA-approved drug, for the treatment of NASH. A Grading of Recommendations, Assessment, Development, and Evaluation assessed systematic search of Cochrane Library, MEDLINE, Scopus, and Google Scholar database was conducted from inception till 31 March 2024. Meta-analyses were carried out in accordance with the PRISMA statement. Heterogeneity was determined to be significant if found above 50%. This meta-analysis encompasses three randomized clinical trials, including a total of 2231 patients. The findings show resmetirom’s significant efficacy in several key outcomes, including improvement in fibrosis risk ratios, 1.67 [95% confidence intervals (CI), 1.26–2.20], reductions in liver fat content (95% CI, −39.58 to −23.5), and enhanced liver fibrosis score (95% CI, −0.37 to −0.13) along with improved levels of liver enzymes. Resmetirom was found to be associated with nausea and diarrhea. This is the first systematic review and meta-analysis to determine the safety and efficacy of resmetirom which showed significant positive results in fibrosis improvement, liver fat content, lipid profiles, and liver enzymes in comparison to placebo. Moreover, moderate side effects, such as diarrhea and nausea, were seen in few patients indicating a satisfactory safety profile.