Comparison of pharmacological therapies in metabolic dysfunction–associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis
Year: 2025
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: BACKGROUND AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) 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 (SUCRA) 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.
Source: Hepatology
Authors: Matheus Souza, Lubna Al-Sharif, Vanio L.J. Antunes, Daniel Q. Huang, Rohit Loomba
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,900
Awards: A Cardiovascular-NASH disease nexus: Common Mechanisms and Treatments?, Non-invasive screening of diabetics for advanced fibrosis due to NAFLD, Ancillary Studies of NAFLD and NASH in HIV infected Adults, QUS Technology for Diagnosis and Grading of Hepatic Steatosis in NAFLD, San Diego Digestive Diseases Research Center, Clinical Research on Nonalcoholic Fatty Liver Disease, San Diego Cirrhosis Clinical Research Network
OpenAlex ID: W4407127207