S2826 Harnessing FGF21: A Meta-Analytic Evaluation of Efruxifermin's Efficacy and Safety in Non-Alcoholic Steatohepatitis

Introduction: Non-alcoholic steatohepatitis (NASH) is a progressive liver disease with limited therapeutic options. Efruxifermin (EFX), a fibroblast growth factor 21 (FGF21) analogue, has emerged as a potential treatment. This meta-analysis evaluates the safety and efficacy of EFX compared to placebo in patients with NASH. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. Randomized controlled trials (RCTs) assessing EFX in NASH patients were identified through comprehensive database searches. Primary endpoints included histological improvements in fibrosis and NASH resolution. Secondary endpoints encompassed changes in liver fat content, metabolic parameters, and safety profiles. Data were analyzed using Review Manager (RevMan) version 5.4. Heterogeneity was assessed using the I² statistic, and a random-effects model was applied due to anticipated clinical heterogeneity among studies. Results: Five RCTs encompassing various stages of NASH (F1–F4 fibrosis) were analyzed. The pooled analysis demonstrated that EFX significantly improved liver histology and metabolic parameters compared to placebo. Specifically, the relative risk (RR) for achieving ≥1-stage fibrosis improvement without NASH worsening was 1.87 (95% CI: 1.15 to 2.92; I² = 45%), indicating a substantial benefit of EFX over placebo. Additionally, EFX treatment led to a significant reduction in liver fat content, with a mean difference (MD) of -13.80% (95% CI: -16.10% to -11.90%; I² = 75%). The most common adverse events associated with EFX were mild to moderate gastrointestinal events, including diarrhea and nausea. Conclusion: Efruxifermin exhibits significant efficacy in improving liver histology and metabolic parameters in NASH patients across fibrosis stages, with a favorable safety profile. These findings support further investigation of EFX in larger, long-term Phase 3 trials to establish its role in NASH management. Additionally, its dual impact on both fibrosis regression and liver fat reduction positions it as a promising disease-modifying agent. Integration of EFX into clinical practice could potentially shift the therapeutic paradigm in NASH, addressing both histologic progression and metabolic dysfunction.