MASH treatments compared in network meta-analysis

Pegozafermin, cilofexor plus firsocostat, and cilofexor plus selonsertib appear to be the most effective interventions for metabolic dysfunction-associated steatohepatitis (MASH), a recent study found.

Researchers performed an updated network meta-analysis to compare the effectiveness of different pharmacological agents for fibrosis regression and for MASH resolution. Studies were included if they were randomized controlled trials published from 2020 to Dec. 1, 2024, that compared pharmacological interventions in patients with biopsy-proven MASH. Fibrosis improvement of at least one stage without worsening of MASH and MASH resolution without worsening of fibrosis were the co-primary endpoints. Treatments were ranked using surface under the cumulative ranking (SUCRA) curve analysis. The results were published Feb. 4 by Hepatology.

Thirty-one studies reporting data from 29 randomized controlled trials, with a total of 9,324 patients, were included in the analysis. Nine of the trials were conducted in North America, three in Asia, and one in Europe, and 16 trials were conducted in multiple countries. Trial duration ranged from 24 to 72 weeks. Pegozafermin, cilofexor plus firsocostat, and cilofexor plus selonsertib were ranked as the most effective interventions overall. For achieving fibrosis regression without worsening MASH, pegozafermin, cilofexor plus firsocostat, denifanstat, survodutide, obeticholic acid, tirzepatide, resmetirom, and semaglutide significantly outperformed placebo. For achieving MASH resolution without worsening fibrosis, pegozafermin, survodutide, tirzepatide, efruxifermin, liraglutide, vitamin E plus pioglitazone, resmetirom, semaglutide, pioglitazone, denifanstat, semaglutide, and lanifibranor were all significantly better than placebo, with pegozafermin, survodutide, and tirzepatide ranked as most effective.

The authors noted that some of the evaluated therapies are no longer being considered for use in MASH and that the included trials involved different populations and different durations, among other limitations. “In conclusion, this network meta-analysis provides contemporaneous and relative rank-order evidence on the efficacy of MASH therapies for achieving fibrosis regression and MASH resolution,” they wrote. “These data may help the development of combination therapies, which are likely to improve histologic response with further treatment of comorbidities.” They called for future head-to-head trials to confirm their findings.