S2857 Efficacy and Safety of Efruxifermin in Patients With MASH: A Meta-Analysis of Randomized Controlled Trials

Introduction: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease marked by steatosis, inflammation, and fibrosis, with few approved treatment options. Efruxifermin, an FGF21 analog, has shown potential in improving both metabolic and histological features of MASH. This analysis evaluates its efficacy across key histological outcomes compared to placebo. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted by searching PubMed, Scopus, Web of Science, and Cochrane CENTRAL through May 28, 2025. Eligible studies included adult patients with MASH and compared efruxifermin with placebo. Meta-analyses were performed using risk ratios (RRs) with 95% confidence intervals for dichotomous outcomes. All statistical analyses were performed using Stata version 19. Results: Four randomized controlled trials comprising 419 patients were included, with 284 patients receiving efruxifermin and 135 receiving placebo. Efruxifermin significantly increased the likelihood of MASH resolution without worsening (RR = 2.42; 95% CI: 1.48–3.94; P < 0.001), ≥1-stage fibrosis improvement without MASH worsening (RR = 1.83; 95% CI: 1.17–2.84; P = 0.01). It also led to significant improvements in MASH resolution and improvement (RR = 3.77; 95% CI: 1.10–12.87; P = 0.03). However, ≥2-stage fibrosis improvement without MASH worsening was not statistically significant. Efruxifermin was associated with a higher risk of drug-related adverse and discontinuations due to adverse events, while no significant differences were observed in serious adverse events, deaths, or overall treatment-emergent adverse events. Conclusion: Efruxifermin was associated with improvements in fibrosis, MASH resolution compared to placebo. Additional RCTs are warranted to validate these effects and assess long-term efficacy and safety.