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Digital ILC 2020: Large Japanese study reports that the combination of bezafibrate plus ursodeoxycholic acid (UDCA) improves liver transplant-free survival compared with no treatment or UDCA monotherapy in patients with primary biliary cholangitis

EUROPEAN ASSOCIATION FOR THE STUDY OF THE LIVER (EASL)

27 August 2020: The combination of bezafibrate and ursodeoxycholic acid (UDCA) has been shown to increase transplant-free survival compared with no treatment or UDCA monotherapy in a Japanese cohort study involving a large number of patients with primary biliary cholangitis (PBC). The study, which was reported at the Digital International Liver Congress (DILC) 2020, adds to the growing body of evidence suggesting that the addition of bezafibrate to UDCA therapy improves both biochemical markers and long-term outcomes in PBC, especially in patients with an inadequate response to UDCA.1–3

PBC is an immune-mediated liver disease that is characterized by the development of serum autoantibodies, inflammation, the destruction of small intrahepatic bile ducts, progressive cholestasis, and a slow progression towards cirrhosis and liver failure.1,2 UDCA is the recommended first-line pharmacological treatment for PBC in Europe.4 However, around 20% of patients show an inadequate response to UDCA,5 and these patients are at greater risk of hepatic complications and more likely to need liver transplantation than treatment responders.5,6

Bezafibrate is a hypolipidaemic fibrate that is currently approved for the treatment of PBC in France.2 It has been used in Japan as a second-line treatment for patients with PBC and an incomplete response to UDCA for more than a decade,3 enabling an assessment of its long-term efficacy as a combination treatment.

The study, presented at the DILC 2020, was a retrospective analysis of 8,180 PBC patients of whom 6,087 (74%) received UDCA monotherapy, 943 (12%) received a combination of UDCA and bezafibrate, and 1,133 (14%) received no treatment; the remaining 17 patients received bezafibrate monotherapy. Patients treated with UDCA monotherapy had a significantly lower risk of all-cause death or liver transplantation than those receiving no treatment; the adjusted hazard ratio (aHR) was 0.55 (95% confidence interval [CI] 0.47, 0.65; p<0.0001). The addition of bezafibrate to UDCA conferred a further risk reduction compared with UDCA monotherapy, with an aHR of 0.23 (95% CI 0.15, 0.35; p<0.0001). Results were similar when considering a combined outcome of liver-related death or liver transplant.

“Ideally, the long-term effectiveness of UDCA and bezafibrate should be assessed in prospective, randomized, placebo-controlled studies”, said Dr Atsushi Tanaka from the Teikyo University School of Medicine in Tokyo, Japan, who presented the study findings. “This is challenging in Japan because bezafibrate is a standard-of-care second-line treatment”.

“However, this study evaluated a large nationwide cohort of PBC patients, and the addition of bezafibrate to UDCA produced enhanced long-term benefits, markedly reducing the risk of all-cause death or liver transplantation compared with UDCA treatment alone. As response to UDCA can now be anticipated from pre-treatment features, a new treatment approach may be to start bezafibrate combination therapy immediately in patients with a predicted poor response to UDCA”.

“Prospective, randomized, placebo-controlled trials of adequate size and duration are a golden standard to demonstrate the efficacy of novel therapeutic interventions in diseases for which treatment options are limited”, said Professor Ulrich Beuers of the Tytgat Institute for Liver and Intestinal Research in Amsterdam, The Netherlands, and an EASL Governing Board member. “Retrospective analyses can also lead to enormous knowledge gain when carefully performed. In PBC, UDCA (13–15 mg/kg/day) is the standard of care for all patients. Japanese clinicians and researchers were the first to combine UDCA with bezafibrate treatment in patients who did not respond adequately to UDCA alone. The retrospective analysis presented by Professor Tanaka, representing a large group of Japanese hepatologists, summarizes the Japanese long-term experience with UDCA and bezafibrate in a cohort of more than 8000 PBC patients. This report, together with well-designed prospective studies, will have major impact for the future management of PBC worldwide and deserves deep appreciation for the efforts of our Japanese colleagues”.

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About The International Liver Congress™

This annual congress is EASL’s flagship event, attracting scientific and medical experts from around the world to learn about the latest in liver research and exchange clinical experience. Attending specialists present, share, debate, and conclude on the latest science and research in hepatology, working to enhance the treatment and management of liver disease in clinical practice. This year, the congress is being held entirely digitally due to the global health situation. The Digital International Liver Congress™ 2020 will take place from 27–29 August 2020. For more information on attendance and registration, please visit https://ilc-congress.eu/.

About The European Association for the Study of the Liver (EASL)

Since its foundation in 1966, this not-for-profit organization has grown to over 4,500 members from all over the world, including many of the leading hepatologists in Europe and beyond. EASL is the leading liver association in Europe, having evolved into a major European association with international influence, and with an impressive track record in promoting research in liver disease, supporting wider education, and promoting changes in European liver policy.

Contact

For more information or to speak to an expert, please contact Sean Deans in the ILC Press Office at:

Session details

Session title: General session I
Date and time of session: Thursday 27 August 2020, 13.15–13.30
Presenter: Atsushi Tanaka
Abstract: Bezafibrate add-on therapy improves liver transplantation-free survival in patients with primary biliary cholangitis: a Japanese nationwide cohort study (GS01)

Author disclosures

Atsushi Tanaka reports receiving consultant fees from EA Pharma, Gilead Sciences, and GlaxoSmithKline. Among the study co-authors: Bettina Hansen has received unrestricted grants and consultant fees from Albireo, Calliditas, Cymabay, Intercept, and Mirum, and consultant fees from ChemoMab and Genfi; Olivier Chazouillères has received grant support from Aptalis, fees for teaching from Mayoly Spindler, consulting fees from Genfit, and fees for teaching and consulting fees from Intercept; and Christophe Corpechot has received grants from Arrow and Intercept France, consulting fees from GenKyoTex, Intercept France, and Inventiva Pharma, and fees for teaching from GlaxoSmithKline France and Intercept France. No other potential conflicts of interest relevant to this study are reported.

References

  1. Corpechot C, et al. A placebo-controlled trial of bezafibrate in primary biliary cholangitis. N Engl J Med.2018;378(23):2171–81.
  2. Agrawal R, et al. Effectiveness of bezafibrate and ursodeoxycholic acid in patients with primary biliary cholangitis: a meta-analysis of randomized controlled trials. Ann Gastroenterol. 2019;32(5):489–97.
  3. Honda A, et al. Bezafibrate improves GLOBE and UK-PBC scores and long-term outcomes in patients with primary biliary cholangitis. Hepatology. 2019;70(6):2035–46.
  4. European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol.2017;67(1):145–72.
  5. Harms MH, et al. Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis. J Hepatol. 2019;71(2):357–65.
  6. Harms MH, et al. Major hepatic complications in ursodeoxycholic acid-treated patients with primary biliary cholangitis: risk factors and time trends in incidence and outcome. Am J Gastroenterol. 2018;113(2):254–64.
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