A total of 29 randomized controlled trials involving 9,324 patients were analyzed for the efficacy of pharmacological agents in treating metabolic dysfunction-associated steatohepatitis ().
Pegozafermin, cilofexor + firsocostat, and cilofexor + selonsertib were ranked as the most effective for achieving fibrosis regression without worsening MASH.
Pegozafermin, survodutide, and tirzepatide were identified as the leading agents for achieving MASH resolution without worsening fibrosis.
Multiple pharmacological agents significantly outperformed placebo in both fibrosis regression and MASH resolution.
The study utilized surface under the cumulative ranking curve () analysis to evaluate the comparative efficacy of treatments.
Simplified
BACKGROUND AND AIMS: Metabolic dysfunction-associated steatohepatitis () is a leading cause of liver disease. With the advent of multiple therapeutic targets in late-phase clinical drug development for MASH, there is a knowledge gap to better understand the comparative efficacy of various pharmacological agents. We conducted an updated network meta-analysis to evaluate the relative rank order of the different pharmacological agents for both fibrosis regression and MASH resolution.
APPROACH AND RESULTS: We searched PubMed and Embase databases from January 1, 2020 to December 1, 2024, for published randomized controlled trials comparing pharmacological interventions in patients with biopsy-proven MASH. The co-primary endpoints were fibrosis improvement ≥1 stage without MASH worsening and MASH resolution without worsening fibrosis. We conducted surface under the cumulative ranking curve () analysis. A total of 29 randomized controlled trials (n=9324) were included. Pegozafermin, cilofexor + firsocostat, denifanstat, survodutide, obeticholic acid, tirzepatide, resmetirom, and semaglutide were significantly better than placebo in achieving fibrosis regression without worsening MASH. Pegozafermin (SUCRA: 79.92), cilofexor + firsocostat (SUCRA: 71.38), and cilofexor + selonsertib (SUCRA: 69.11) were ranked the most effective interventions. Pegozafermin, survodutide, tirzepatide, efruxifermin, liraglutide, vitamin E + pioglitazone, resmetirom, semaglutide, pioglitazone, denifanstat, semaglutide, and lanifibranor were significantly better than placebo in achieving MASH resolution without worsening fibrosis. Pegozafermin (SUCRA: 91.75), survodutide (SUCRA: 90.87), and tirzepatide (SUCRA: 84.70) were ranked the most effective interventions for achieving MASH resolution without worsening fibrosis.
CONCLUSIONS: This study provides updated rank-order efficacy of MASH pharmacological therapies for fibrosis regression and MASH resolution. These data are helpful to inform practice and clinical trial design.
Key numbers
79.92
Highest for Improvement
Rank for without worsening .
91.75
Highest for
Rank for without worsening .
Full Text
We can’t show the full text here under this license.
Daniel Q. Huang consults for, advises, and is on the speakers' bureau for Roche. He consults for and advises Gilead. Rohit Loomba consults for and received grants from Arrowhead, AstraZeneca, Eli Lilly, Gilead, Intercept, Inventiva, Ionis, Janssen, Madrigal, Merck, Novo Nordisk, Pfizer, and Terns. He consults for Aardvark, Altimmune, Cascade, Glympse Bio, Inipharma, Lipidio, Neurobo, Sagimet, 89 Bio, Takeda, and Viking. He received grants from Boehringer-Ingelheim, Bristol-Myers Squibb, Galectin, Hanmi, and Sonic Incytes. He has stock options in Sagimet Biosciences and is a co-founder of LipoNexus Inc. The remaining authors have no conflicts to report.
