Comparative efficacy of pharmacologic therapies for MASLD in improving fibrosis: systematic review and network meta-analysis

Fibrosis is a key predictor of the long-term prognosis in metabolic dysfunction-associated steatotic liver disease (MASLD). Numerous clinical trials in drug development for MASLD have used fibrosis improvement as an efficacy endpoint. We aim to compare the efficacy of pharmacologic therapies for MASLD in improving fibrosis using histopathological and noninvasive assessments. A comprehensive search for randomized controlled trials (RCTs) was conducted across multiple databases, focusing on drug therapy in adult patients with MASLD. The primary outcome was more than 1-stage fibrosis improvement. The secondary outcomes included changes in liver stiffness measurement (LSM) via vibration-controlled transient elastography (VCTE) and magnetic resonance elastography. Each intervention's ranking probability was assessed using the surface under the cumulative ranking curve (SUCRA). Forty-eight RCTs involving 10 119 participants were included. For the primary outcome, pegozafermin, obeticholic acid (OCA), and resmetirom all outperformed placebo in the fibrosis stage F1-3 analysis. OCA was superior to placebo in the 1.5-year analysis. Pegbelfermin (SUCRA: 77.11%) and pegozafermin (SUCRA: 74.91%) at F1-3, and OCA at 1.5 years (SUCRA: 81.64%) were ranked as the most effective treatments. For the secondary outcome, pegozafermin significantly outperformed placebo for decreasing LSM via VCTE in 0.5-year analysis, ranking as the most effective treatment for this outcome (SUCRA: 96.98%). Several new drugs currently in clinical trials have shown potential therapeutic effects for fibrosis improvement in MASLD patients, especially those targeting fibroblast growth factor 21 (FGF21). More definitive efficacy will depend on the results of phase III clinical trials.