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The ethics of unlicensed therapy use in primary biliary cholangitis: a counter view

Nature Reviews Gastroenterology & Hepatology (2026)Cite this article

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Corpechot and colleagues recently argued for an ‘ethical imperative’ to use off-licence bezafibrate to treat primary biliary cholangitis (PBC), despite the availability of several licensed therapies (Bezafibrate for primary biliary cholangitis: time to act on the evidence. Nat. Rev. Gastroenterol. Hepatol. 22, 805–807 (2025))1. Here, we present an alternative view.

Outcomes in PBC have improved markedly with a treatment approach of first-line ursodeoxycholic acid, followed by second-line agents in patients showing incomplete response. Bezafibrate has played a part as one such second-line therapy2; however, it remains unlicensed for use in PBC and has undergone only limited formal safety and efficacy evaluation. By contrast, newer peroxisome proliferator-activated receptor (PPAR) agonists (elafibranor and seladelpar)3,4 and the farnesoid X receptor agonist obeticholic acid (OCA)5 were developed specifically for PBC and have undergone full regulatory scrutiny. Corpechot and colleagues argue that bezafibrate is safer, more effective and cheaper than licensed alternatives, but here we ask how these agents actually compare (Table 1).

Table 1 Characteristics of the licensed and unlicensed second-line therapies currently used in primary biliary cholangitis
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References

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Author information

Authors and Affiliations

  1. Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK

    David E. J. Jones

  2. PBC Foundation, Edinburgh, UK

    Robert Mitchell-Thain

  3. Translational Gastroenterology and Liver Unit, John Radcliffe Hospital, Oxford, UK

    Emma L. Culver

  4. National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre, Oxford, UK

    Emma L. Culver

  5. Liver Unit, Freeman Hospital, Newcastle upon Tyne, UK

    Jessica K. Dyson

  6. Hepatitis B Foundation, San Diego, CA, USA

    Robert G. Gish

  7. Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA

    Robert G. Gish

  8. Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands

    Bettina E. Hansen

  9. IHPME, University of Toronto, Toronto, Ontario, Canada

    Bettina E. Hansen

  10. Toronto Center for Liver Disease, University Health Network, Toronto, Ontario, Canada

    Bettina E. Hansen

  11. The Autoimmune and Rare Liver Disease Programme, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto, Ontario, Canada

    Gideon M. Hirschfield

  12. Liver Institute Northwest, Elson S. Floyd College of Medicine, Washington State University, Pullman, WA, USA

    Kris V. Kowdley

  13. Velocity Clinical Research, Seattle, WA, USA

    Kris V. Kowdley

  14. Department of Biomedical Sciences, Humanitas University, Milan, Italy

    Ana Lleo

  15. Internal Medicine and Liver Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy

    Ana Lleo

  16. Department of Gastroenterology and Hepatology, University Hospital Zürich, University of Zürich, Zurich, Switzerland

    Andreas E. Kremer

  17. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Marlyn J. Mayo

  18. University of Calgary, Calgary, Alberta, Canada

    Mark G. Swain

  19. Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria

    Michael Trauner

  20. National Institute for Health and Care Research, Birmingham Biomedical Research Centre, Birmingham, UK

    Palak J. Trivedi

  21. Liver Unit, University Hospitals Birmingham, Birmingham, UK

    Palak J. Trivedi

  22. Section of Gastroenterology & Hepatology, Baylor Health, Houston, TX, USA

    John M. Vierling

  23. Gastroenterology and Hepatology, Nepean Hospital, Kingswood, New South Wales, Australia

    Martin Weltman

  24. Aneurin Bevan University Health Board, Gwent Liver Unit, Newport, UK

    Andrew D. Yeoman

  25. Division of Digestive Health and Liver Diseases and Schiff Center for Liver Diseases, University of Miami, Miami, FL, USA

    Cynthia Levy

  26. Division of Gastroenterology and Centre for Autoimmune Liver Disease, University of Milano-Bicocca, Milan, Italy

    Marco Carbone

  27. Liver Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy

    Marco Carbone

Authors
  1. David E. J. Jones
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  2. Robert Mitchell-Thain
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  3. Emma L. Culver
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  7. Gideon M. Hirschfield
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  11. Marlyn J. Mayo
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  14. Palak J. Trivedi
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  15. John M. Vierling
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  17. Andrew D. Yeoman
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  19. Marco Carbone
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Corresponding author

Correspondence to David E. J. Jones.

Ethics declarations

Competing interests

The authors are all either officers or medical advisors to the PBC Foundation. All the authors other than R.M.-T. (who is a patient representative) are clinicians who are experienced investigators and have contributed to the development of licensed therapies in PBC.

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Jones, D.E.J., Mitchell-Thain, R., Culver, E.L. et al. The ethics of unlicensed therapy use in primary biliary cholangitis: a counter view. Nat Rev Gastroenterol Hepatol (2026). https://doi.org/10.1038/s41575-026-01179-8

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