Herring WL, Gould IG, Wittrup-Jensen V, Kuti E, Mettam S, Ertle J, Wolowacz S. A conceptual model for the economic evaluation of emerging nonalcoholic steatohepatitis therapies: the impact of treatment efficacy profiles on health outcomes. Poster presented at the 2020 SMDM 18th Biennial European Conference (Conference cancelled); June 16, 2020.

PURPOSE: Nonalcoholic steatohepatitis (NASH) is a leading cause of liver transplantation and the focus of ongoing drug development efforts. This study presents a modeling approach for the economic evaluation of emerging NASH therapies and investigates the impact on health outcomes of different treatment efficacy profiles.

: We designed a Markov model structure informed by published economic and epidemiology studies to capture the natural history of NASH and associated liver complications. The structure used an annual cycle length and included health states for NASH fibrosis stages F0-F3, NASH resolution fibrosis stages F0-F3, compensated cirrhosis (F4), liver-related complications (LRC) (decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, and liver-related death), and all-cause death. Standard of care (SoC) transition probabilities and mortality rates were obtained from published literature, and outcomes were validated against long-term observational data. Based on clinical trial endpoints (reflecting different treatment mechanisms), we considered three hypothetical efficacy profiles modifying the SoC transition probabilities for NASH resolution (hazard ratio [HR] = 2.0), fibrosis improvement (HR = 2.0), and fibrosis worsening (HR = 0.5). We used the model to estimate 10-year LRC rates and lifetime discounted (3% annually) life-years (LYs) for cohorts starting in fibrosis stages F1 through F4 for each efficacy profile (the NASH resolution profile was not applicable [NA] for F4). Patients were treated for 2 years or until leaving the baseline fibrosis stage.

RESULT: For patients receiving the SoC, 10-year LRC rates increased with baseline fibrosis stage (F1: 3.3%; F2: 10.6%; F3: 28.9%; F4: 67.9%) while lifetime discounted LYs decreased (F1: 17.4; F2: 16.4; F3: 14.1; F4: 9.0). Of the three efficacy profiles, slowing fibrosis worsening had the largest impact on 10-year LRC rates (F1: 2.3%; F2: 8.0%; F3: 22.9%; F4: 64.2%) and lifetime discounted LYs (F1: 17.6; F2: 16.8; F3: 14.8; F4: 9.5). The NASH resolution/fibrosis improvement profiles were comparable in their impact on 10-year LRC rates (F1: 2.9%/2.9%; F2: 9.3%/9.1%; F3: 25.1%/24.7%; F4: NA/64.1%) and lifetime discounted LYs (F1: 17.5/17.5; F2: 16.6/16.6; F3: 14.6/14.6; F4: NA/9.4).

CONCLUSION: As emerging therapies for NASH near the market, a comprehensive modeling approach will be necessary to assist decision makers conducting economic evaluations of these treatments. This analysis demonstrates the impact of different efficacy profiles on long-term NASH outcomes, and thus the potential cost-effectiveness of NASH treatments.

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