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Hepatology
Original research
Number needed to treat with ursodeoxycholic acid therapy to prevent liver transplantation or death in primary biliary cholangitis
  1. Maren H Harms1,
  2. Rozanne C de Veer1,
  3. Willem J Lammers1,
  4. Christophe Corpechot2,
  5. Douglas Thorburn3,
  6. Harry L A Janssen4,
  7. Keith D Lindor5,6,
  8. Palak J Trivedi7,
  9. Gideon M Hirschfield4,7,
  10. Albert Pares8,
  11. Annarosa Floreani9,
  12. Marlyn J Mayo10,
  13. Pietro Invernizzi11,
  14. Pier Maria Battezzati12,
  15. Frederik Nevens13,
  16. Cyriel Y Ponsioen14,
  17. Andrew L Mason15,
  18. Kris V Kowdley16,
  19. Bettina E Hansen4,
  20. Henk R van Buuren1,
  21. Adriaan J van der Meer1
  1. 1 Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
  2. 2 Service d'Hépatologie, Centre de Référence des Maladies Inflammatoires des Voies Biliaires, Hôpital Saint-Antoine, APHP, Paris, France
  3. 3 The Sheila Sherlock Liver Centre and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
  4. 4 Toronto Centre for Liver Disease, Francis Family Liver Clinic, Toronto Western Hospital Liver Centre, Toronto, Ontario, Canada
  5. 5 College of Health Solutions, Arizona State University, Phoenix, Arizona, USA
  6. 6 Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
  7. 7 Birmingham NIHR Biomedical Research Centre and Centre for Liver Research, University of Birmingham, Birmingham, UK
  8. 8 Liver Unit, Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
  9. 9 Department of Surgery, Oncology and Gastroenterology, Universita degli Studi di Padova, Padova, Italy
  10. 10 Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
  11. 11 Division of Gastroenterology and Program for Autoimmune Liver Diseases, International Center for Digestive Health, Department of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy
  12. 12 Department of Health Sciences, University of Milan, Milano, Italy
  13. 13 Department of Hepatology, UZ Leuven, Leuven, Belgium
  14. 14 Department of Gastroenterology and Hepatology - location Academic Medical Center, Amsterdam University Medical Centres, Amsterdam, The Netherlands
  15. 15 Division of Gastroenterology and Hepatology, University of Alberta, Edmonton, Alberta, Canada
  16. 16 Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, Washington, USA
  1. Correspondence to Adriaan J van der Meer, Dept of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam 3015 GD, The Netherlands; a.vandermeer{at}erasmusmc.nl

Abstract

Objective The clinical benefit of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has never been reported in absolute measures. The aim of this study was to assess the number needed to treat (NNT) with UDCA to prevent liver transplantation (LT) or death among patients with PBC.

Methods The NNT was calculated based on the untreated LT-free survival and HR of UDCA with respect to LT or death as derived from inverse probability of treatment weighting-adjusted Cox proportional hazard analyses within the Global PBC Study Group database.

Results We included 3902 patients with a median follow-up of 7.8 (4.1–12.1) years. The overall HR of UDCA was 0.46 (95% CI 0.40 to 0.52) and the 5-year LT-free survival without UDCA was 81% (95% CI 79 to 82). The NNT to prevent one LT or death within 5 years (NNT5y) was 11 (95% CI 9 to 13). Although the HR of UDCA was similar for patients with and without cirrhosis (0.33 vs 0.31), the NNT5y was 4 (95% CI 3 to 5) and 20 (95% CI 14 to 34), respectively. Among patients with low alkaline phosphatase (ALP) (≤2× the upper limit of normal (ULN)), intermediate ALP (2–4× ULN) and high ALP (>4× ULN), the NNT5y to prevent one LT or death was 26 (95% CI 15 to 70), 11 (95% CI 8 to 17) and 5 (95% CI 4 to 8), respectively.

Conclusion The absolute clinical efficacy of UDCA with respect to LT or death varied with baseline prognostic characteristics, but was high throughout. These findings strongly emphasise the incentive to promptly initiate UDCA treatment in all patients with PBC and may improve patient compliance.

  • primary biliary cirrhosis
  • clinical decision making
  • hepatobiliary disease
  • liver
https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/gutjnl-2019-319057

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    Footnotes

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    • Presented at This study was previously presented as an abstract at the following conferences: The Liver Meeting 2016, American Association for the Study of Liver Diseases, 11–15 November 2016, Boston, USA; and the International Bile Acid Meeting: Bile Acids in Health and Disease 2018, 6–7 July 2018, Dublin, Ireland.

    • Contributors Guarantor of the article: MHH and AJvdM. MHH and AJvdM had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of data analyses. Study concept and design: MHH, RCdV, WL, CC, DT, HLAJ, KL, PT, GH, AP, AF, MM, PI, PMB, FN, CYP, AM, KK, BEH, HvB, AJvdM. Acquisition of data: MHH, WL, CC, DT, HLAJ, KL, PT, GH, AP, AF, MM, PI, PMB, FN, CYP, AM, KK, BEH, HvB, AJvdM. Analysis and interpretation of data: MHH, RCdV, AJvdM. Drafting of the manuscript: MHH, RCdV, CC, DT, BEH, HvB, AJvdM. Critical revision of the manuscript for important intellectual content: MHH, RCdV, WL, CC, DT, HLAJ, KL, PT, GH, AP, AF, MM, PI, PMB, FN, CYP, AM, KK, BEH, HvB, AJvdM. Statistical analysis: MHH, AJvdM. Obtained funding: BEH, HvB. Study supervision: MHH, RCdV, WL, CC, DT, HLAJ, KL, PT, GH, AP, AF, MM, PI, PMB, FN, CYP, AM, KK, BEH, HvB, AJvdM.

    • Funding This investigator-initiated study was supported by an unrestricted grant from Intercept Pharmaceuticals and was funded by the Foundation for Liver and Gastrointestinal Research (a not-for-profit foundation) in Rotterdam, the Netherlands. The supporting parties had no influence on the study design, data collection and analyses, writing of the manuscript, or on the decision to submit the manuscript for publication.

    • Competing interests MHH reports a speaker fee from Zambon Nederland. WL reports consulting services for Intercept Pharmaceuticals. CC is a consultant for Intercept Pharmaceuticals France. DT reports consulting activities for Intercept Pharmaceuticals. HLAJ reports grants from and consulting work for AbbVie Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences, Innogenetics, Merck, Novartis, Roche, Intercept Pharmaceuticals and Janssen. KL reports that he is an unpaid advisor for Intercept Pharmaceuticals and Shire. PT receives institutional salary support from the NIHR Birmingham Liver Biomedical Research Centre. He received research grant funding from the Wellcome Trust, Guts UK, PSC Support and Intercept Pharmaceuticals. He also received advisory and consultancy fees from Intercept and Dr Falk Pharma, and speaker fees from Intercept, Dr Falk Pharma, Zambon and Perspectum Diagnostics. GH reports advisory services for Intercept Pharmaceuticals, Novartis and GlaxoSmithKline Pharmaceuticals. AP reports consulting services for Intercept Pharmaceuticals and Novartis Pharma. AF reports consulting activities for Intercept Pharmaceuticals. PI reports personal fees from Intercept and non-financial support from Bruschettini and Menarini Diagnostics. CYP has received grant support form Takeda, speaker’s fees from AbbVie, Takeda and Dr Falk Pharma, and served as a consultant for Takeda and Pliant. AM reports advisory services for Intercept Pharmaceuticals, AbbVie and Novartis, and research funding resources from the Canadian Institutes of Health Research, Canadian Liver Foundation, American Kennel Club, Intercept Pharmaceuticals, AbbVie and Gilead Sciences. KK reports personal fees from Gilead Sciences, Intercept Pharmaceuticals and Novartis, and grants from Gilead Sciences and Intercept Pharmaceuticals. BEH reports grants from Intercept Pharmaceuticals and Zambon Nederland, and consulting work for Intercept Pharmaceuticals and Novartis. HvB is a consultant for Intercept Pharma Benelux and received unrestricted research grants from Intercept Pharmaceuticals and from Zambon Nederland. AJvdM reports speaker's fees from MSD, Gilead Sciences, AbbVie Pharmaceuticals and Zambon Nederland, received an unrestricted grant from Gilead Sciences, and reports travel expenses covered by Dr Falk Pharma.

    • Patient consent for publication Not required.

    • Ethics approval This study was conducted in accordance with the Declaration of Helsinki. The protocol was approved by the institutional research board of the corresponding centre and at each participating centre, in accordance with their local regulations.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement No data are available.

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