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Research Article
1 November 2022

Evaluation of emerging NASH therapies: the impact of treatment efficacy profiles on long-term health outcomes

Authors: William L Herring https://orcid.org/0000-0001-8222-9914 [email protected], Ian Gopal Gould https://orcid.org/0000-0002-5566-7668, Villum Wittrup-Jensen, Judith Ertle, Effie Kuti, and Sorrel Wolowacz https://orcid.org/0000-0001-5497-612XAuthor Info & Affiliations
Volume 11, Number 18
https://doi.org/10.2217/cer-2021-0194
PDFFormats

Abstract

Aim: Evaluations of nonalcoholic steatohepatitis (NASH) treatments require predicting lifetime outcomes from short-term clinical trials. Materials & methods: A Markov model with NASH fibrosis stages F0–F3, NASH resolution, compensated cirrhosis (F4/CC), and liver-related complication (LRC) states was developed using literature-based standard of care (SoC) data. Hypothetical efficacy profiles were defined affecting resolution (100%-increase), fibrosis improvement (100% increase), or fibrosis worsening (50% decrease). Results: For the SoC, 10-year LRC rates increased with baseline fibrosis stage (F1: 3.0%; F2: 9.8%; F3: 27.2%; F4/CC: 64.9%). The fibrosis worsening profile reduced predicted 10-year LRC rates (F1: 1.9%; F2: 6.5%; F3: 19.1%; F4/CC: 55.0%) more than the resolution and fibrosis improvement profiles (F1: 2.6%/2.6%; F2: 8.5%/8.3%; F3: 23.3%/23.0%; F4/CC: NA/59.0%). Scenario analyses considered alternative SoC progression, treatment efficacy and treatment-stopping rules. Conclusion: Potential NASH efficacy profiles have differing impacts on predicted long-term outcomes, providing insights for future stakeholders.

Plain language summary

Many new treatments are being investigated for nonalcoholic steatohepatitis (NASH), a progressive and life-threatening disease often resulting in liver fibrosis (scarring) and advanced liver disease. The clinical value of these treatments and whether they are good value for money will depend on their ability to reduce the risk of advanced liver disease and subsequent liver transplantation. We developed a disease progression model which tracks survival and quality of life for two identical groups of NASH patients over their lifetimes. One group received a new hypothetical treatment for NASH while the other received current standard care. We used the model to estimate the potential health benefits of different hypothetical treatments for NASH. Our results suggest that treatments slowing fibrosis worsening may lead to greater long-term health benefits than treatments that improve NASH or improve existing fibrosis. These findings may provide insights to researchers involved in the development of new treatments for NASH.

Supplementary Material

File (supplementary material.docx)

References

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