Comparative Efficacy and Safety of Resmetirom and Efruxifermin for Metabolic Dysfunction-Associated Steatohepatitis:...

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver condition and a major cause of cirrhosis, hepatocellular carcinoma, and liver transplantation. Resmetirom, a thyroid hormone receptor β agonist, and Efruxifermin, a fibroblast growth factor 21 analogue, have shown promise in improving hepatic fat fraction (HFF) and liver enzyme levels. This study systematically compares the efficacy and safety of Resmetirom and Efruxifermin in treating MASH.

A systematic search of PubMed, Cochrane, and Scopus identified 211 studies, of which eight randomized controlled trials (RCTs) were included. Primary outcomes included reductions in liver enzyme levels. Secondary outcomes assessed HFF measured by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF), as well as lipid profiles. Safety outcomes consist of serious adverse events and events leading to treatment discontinuation.

Efruxifermin was associated with significant improvement in MRI-PDFF with an mean difference (MD) of -62.83% (95% CI: -72.30 to -53.36, p = 0.00), followed by Resmetirom with an MD of -37.15% (95% CI: -44.43 to -29.88, p = 0.00), additionally Efruxifermin was associated with significant reduction in aspartate transferase (AST) level, with an MD of -14.32 (95% CI: -23.92 to -4.72, p = 0.003), compared to Resmetirom (MD: -2.81; 95% CI: -12.40 to 6.79, p = 0.56). For lipid profiles, Efruxifermin showed a significant reduction in triglyceride levels with an MD of -36.95 (95% CI: -52.67 to -21.24, p = 0), while Resmetirom had an MD of -24.72 (95% CI: -33.31 to -16.14, p = 0.00).

Efruxifermin demonstrated a slightly greater effect on MRI-PDFF and AST, along with more favourable safety outcomes.