Efficacy and safety of resmetirom among patients with Non-alcoholic steatohepatitis: a systematic review and Meta-Analysis

Abstract

Nonalcoholic 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 non-alcoholic steatohepatitis (NASH). PubMed, SCOPUS and Cochrane Central were searched till March 2024 to find potential articles. Outcomes assessed included MRI-PDFF, Fat Reduction, and NASH Resolution Without Fibrosis, changes in AST, ALT, GGT, LDL, and triglyceride (TG) levels, along with diarrhea, nausea, UTI, and headache. Subgroup analysis was performed between outcomes before and after 6 months. Outcomes were analyzed with 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. Risk of bias assessment was performed using Cochrane Risk of Bias tool. Four RCTs were included in our analysis. Resmetirom shown a substantial improvement in MRI-PDFF with a mean difference of -19.23 (P<0.00001). Additionally, it resulted in a 30% reduction in fat (odds ratio: 3.54, P=0.004) and resolution of NASH without fibrosis (odds ratio: 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 (mean difference: -4.36, P-value: 0.32), GGT levels (mean difference: -17.87, P-value: <0.00001), TG levels (mean difference: -23.48, P-value: <0.00001), LDL levels (mean difference: -12.80, P-value: <0.00001), and rT3 levels (mean difference: -2.08, P-value: <0.00001). The use of Resmetirom was associated with a higher likelihood of experiencing diarrhea (odds ratio [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 urinary tract infections (UTI) (OR: 1.04, P=0.85) or headaches (OR: 0.79, P=0.48). Resmetirom demonstrates efficacy in enhancing MRI-PDFF score, diminishing adipose tissue, resolving NASH without fibrosis, reducing GGT, TG, LDL, rT3 levels in NASH patients. Nevertheless, there is also an observed heightened susceptibility to experiencing diarrhea and nausea. Additional trials are necessary to further examine the efficacy and safety of this medication.