Impact of Delayed Treatment Initiation With Resmetirom in Patients With Noncirrhotic Non-Alcoholic Steatohepatitis (NASH) With Moderate to Advanced Fibrosis

OBJECTIVES: Resmetirom is FDA-approved for adults with noncirrhotic NASH with moderate-to-advanced liver fibrosis. This study aims to quantify the impact of delayed NASH treatment initiation on associated costs and clinical outcomes in patients with F2 and F3 fibrosis.

METHODS: A decision-analytic Markov model was developed to simulate fibrosis progression and the onset of advanced liver complications. Using a US setting, the model assessed the effects of annual delays in NASH treatment initiation over 10 years, comparing outcomes with those of patients receiving timely treatment with resmetirom (100mg).

RESULTS: Over a 3-year period, F2 patients experienced an annual average decrease in overall survival (OS) by 1.77% and F3 patients’ OS decreased by 1.44% for every year their treatment was delayed. Quality-adjusted life-years (QALYs) also declined annually by 2.27% for F2 and 1.90% for F3 patients. Untreated patients experienced advanced liver complications more rapidly than those receiving resmetirom. Yearly treatment delays in F2 patients resulted in 2.9% more cases of decompensated cirrhosis (DCC) and hepatocellular carcinoma (HCC), and 3.35% more liver transplants (LT). In F3 patients, this resulted in 3.0% more DCC, 3.1% more HCC, and 3.41% more LT cases per year, over three years. Consequently, the total additional costs per patient for liver disease management ranged from $20,196 to $29,376 after a one-year delay, to up to $47,917 and $55,114 after a 3-year delay for F2 and F3 patients, respectively. An annual average increase of 8.9%-10.3% in costs of liver fibrosis and complication management was observed, with liver transplantation showing the highest cost increase, ranging from 15.8% in F2 to 16.0% in F3 patients.

CONCLUSIONS: Incorrect or late diagnoses that lead to treatment delays in patients with F2–F3 fibrosis exacerbate disease severity and negatively impact patient outcomes. Timely treatment initiation with resmetirom is crucial to prevent rapid disease progression and manage associated healthcare costs effectively.