Efficacy and safety of resmetirom among patients with non-alcoholic steatohepatitis: a systematic review and meta-analysis

Background: Non-alcoholic steatohepatitis (NASH) is a severe medical illness that has few available therapeutic options. Resmetirom, a liver-targeting agonist of the thyroid hormone receptor (THR), has recently been licenced by the FDA. We assess the effectiveness and safety of resmetirom in patients with NASH. Methods: PubMed, SCOPUS and Cochrane Central were searched till March 2024 to find potential articles. Outcomes assessed included MRI-proton density fat fraction (MRI-PDFF), Fat Reduction, and NASH Resolution Without Fibrosis, changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), low-density lipoprotein (LDL), and triglyceride (TG) levels, along with diarrhoea, nausea, urinary tract infection (UTI), and headache. Subgroup analysis was performed between outcomes before and after 6 months. Outcomes were analyzed with a random-effects model and results presented as mean difference (MD) for continuous outcomes and odds ratios (OR) for safety analysis, along with their 95% confidence intervals. A risk of bias assessment was performed using Cochrane Risk of Bias tool. Results: Four randomized controlled trials (RCTs) were included in our analysis. Resmetirom shown a substantial improvement in MRI-PDFF with a MD of -19.23 (P<0.00001). Additionally, it resulted in a 30% reduction in fat (OR: 3.54, P=0.004) and resolution of NASH without fibrosis (OR: 2.41, P=0.04). There was no notable enhancement observed in AST levels, with a mean difference of -0.87 and a P value of 0.73. The usage of resmetirom resulted in significant improvement in ALT levels (MD: -4.36, P value: 0.32), GGT levels (MD: -17.87, P value: <0.00001), TG levels (MD: -23.48, P value: <0.00001), LDL levels (mean difference: -12.80, P value: <0.00001), and rT3 levels (MD: -2.08, P value: <0.00001). The use of Resmetirom was associated with a higher likelihood of experiencing diarrhoea (OR: 2.07, P<0.0001) and nausea (OR: 1.81, P=0.0003). However, there was no significant difference observed in the occurrence of UTI (OR: 1.04, P=0.85) or headaches (OR: 0.79, P=0.48). Conclusion: Resmetirom demonstrates efficacy in enhancing MRI-PDFF score, diminishing adipose tissue, resolving NASH without fibrosis, reducing GGT, TG, LDL, reverse triiodothyronine (rT3) levels in NASH patients. Nevertheless, there is also an observed heightened susceptibility to experiencing diarrhoea and nausea. Additional trials are necessary to further examine the efficacy and safety of this medication.