Clinical and metabolic benefits of efruxifermin in MASH: a GRADE-assessed meta-analysis of randomized trials with...

Efruxifermin, a long-acting FGF21 analog, has shown promising results in adults with metabolic dysfunction-associated steatohepatitis (MASH). We conducted a meta-analysis to evaluate the efficacy and safety of efruxifermin in biopsy-confirmed MASH/NASH.

We searched PubMed, Cochrane Library, Scopus, and Web of Science from inception to 5 June 2025 for randomized controlled trials (RCTs) comparing efruxifermin with placebo. Random-effects models pooled mean differences (MDs) for continuous outcomes and risk ratios (RRs) for binary outcomes with 95% confidence intervals (CIs). Trial sequential analysis (TSA) evaluated whether the accumulated evidence was sufficient for firm conclusions.

Four RCTs (n = 419 patients) were included. Efruxifermin improved ≥ 1-stage fibrosis without MASH worsening (39.7% vs. 17.1%, RR 1.83, 95%CI: [1.17-2.84]) and MASH resolution without worsening (45.1% vs. 13.5%, RR 2.42, 95% CI: [1.48-3.94]). However, TSA suggested the evidence is not yet conclusive. Efruxifermin also reduced ALT (MD -13.97, 95% CI [-23.12; -4.82]), AST (MD -13.24, 95% CI [-21.29; -5.20]), and ELF score (MD -0.66, 95% CI [-0.84; -0.49]). However, no benefit was seen for ≥ 2-stage fibrosis (p = 0.25). Drug-related adverse events (AEs) (71.2% vs. 43.7%%, RR 1.35, 95% CI [1.06-1.71]) and discontinuations (10.3% vs. 2.2%, RR 3.13, 95% CI [1.12-8.76]) increased, but not serious AEs or mortality.

Efruxifermin may produce meaningful histologic and biomarker improvements in MASH, but tolerability may limit persistence. Larger phase III RCTs with longer follow-up are needed to confirm durability, clarify effects in cirrhosis, and better define safety.