TY - JOUR
T1 - Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis
AU - Harms, Maren H.
AU - van Buuren, Henk R.
AU - Corpechot, Christophe
AU - Thorburn, Douglas
AU - Janssen, Harry L.A.
AU - Lindor, Keith D.
AU - Hirschfield, Gideon M.
AU - Parés, Albert
AU - Floreani, Annarosa
AU - Mayo, Marlyn J.
AU - Invernizzi, Pietro
AU - Battezzati, Pier Maria
AU - Nevens, Frederik
AU - Ponsioen, Cyriel Y.
AU - Mason, Andrew L.
AU - Kowdley, Kris V.
AU - Lammers, Willem J.
AU - Hansen, Bettina E.
AU - van der Meer, Adriaan J.
N1 - Funding Information:
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.The following authors declared that they have no conflicts of interest: P.M. Battezzati, F. Nevens, M.J. Mayo. M.H. Harms reports a speaker fee from Zambon Nederland B.V. H.R. van Buuren is a consultant for Intercept Pharma Benelux and received unrestricted research grants from Intercept Pharmaceuticals and from Zambon Nederland B.V. C. Corpechot is consultant for Intercept Pharmaceuticals France. D. Thorburn reports consulting activities for Intercept Pharmaceuticals. K.D. Lindor reports that he is an unpaid advisor for Intercept Pharmaceuticals and Shire. H.L.A. Janssen reports grants from and consulting work for AbbVie Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences, Innogenetics, Merck, Novartis, Roche, Intercept Pharmaceuticals and Janssen. G.M. Hirschfield reports advisory services for Intercept Pharmaceuticals, Novartis and GlaxoSmithKline Pharmaceuticals. A. Parés reports consulting services for Intercept Pharmaceuticals and Novartis Pharma. A. Floreani reports consulting activities for Intercept Pharmaceuticals. P. Invernizzi reports personal fees from Intercept and non-financial support from Bruschettini and Menarini Diagnostics. C.Y. Ponsioen has received grant support form Takeda, speaker's fees from Abbvie, Takeda, and Dr Falk Pharma, and served as consultant for Takeda. A.L. Mason 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 Inc., AbbVie and Gilead Sciences. K.V. Kowdley reports personal fees from Gilead Sciences, Intercept Pharmaceuticals and Novartis; and grants from Gilead Sciences and Intercept Pharmaceuticals. W.J. Lammers reports consulting services for Intercept Pharmaceuticals. B.E. Hansen reports grants from Intercept Pharmaceuticals and Zambon Nederland B.V. and consulting work for Intercept Pharmaceuticals and Novartis. A.J. van der Meer reports speakers fees from MSD, Gilead Sciences, AbbVie Pharmaceuticals and Zambon Nederland B.V., received an unrestricted grant from Gilead Sciences, and report travel expenses covered by Dr. Falk Pharma. This study was performed on behalf of the Global PBC Study Group.
Funding Information:
The following authors declared that they have no conflicts of interest: P.M. Battezzati, F. Nevens, M.J. Mayo. M.H. Harms reports a speaker fee from Zambon Nederland B.V. H.R. van Buuren is a consultant for Intercept Pharma Benelux and received unrestricted research grants from Intercept Pharmaceuticals and from Zambon Nederland B.V. C. Corpechot is consultant for Intercept Pharmaceuticals France. D. Thorburn reports consulting activities for Intercept Pharmaceuticals. K.D. Lindor reports that he is an unpaid advisor for Intercept Pharmaceuticals and Shire. H.L.A. Janssen reports grants from and consulting work for AbbVie Pharmaceuticals , Bristol-Myers Squibb , Gilead Sciences , Innogenetics , Merck , Novartis , Roche , Intercept Pharmaceuticals and Janssen . G.M. Hirschfield reports advisory services for Intercept Pharmaceuticals, Novartis and GlaxoSmithKline Pharmaceuticals. A. Parés reports consulting services for Intercept Pharmaceuticals and Novartis Pharma. A. Floreani reports consulting activities for Intercept Pharmaceuticals. P. Invernizzi reports personal fees from Intercept and non-financial support from Bruschettini and Menarini Diagnostics. C.Y. Ponsioen has received grant support form Takeda , speaker’s fees from Abbvie, Takeda, and Dr Falk Pharma, and served as consultant for Takeda. A.L. Mason 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 Inc., AbbVie and Gilead Sciences. K.V. Kowdley reports personal fees from Gilead Sciences, Intercept Pharmaceuticals and Novartis; and grants from Gilead Sciences and Intercept Pharmaceuticals. W.J. Lammers reports consulting services for Intercept Pharmaceuticals. B.E. Hansen reports grants from Intercept Pharmaceuticals and Zambon Nederland B.V. and consulting work for Intercept Pharmaceuticals and Novartis. A.J. van der Meer reports speakers fees from MSD, Gilead Sciences, AbbVie Pharmaceuticals and Zambon Nederland B.V., received an unrestricted grant from Gilead Sciences, and report travel expenses covered by Dr. Falk Pharma.
Funding Information:
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.
Publisher Copyright:
© 2019 European Association for the Study of the Liver
PY - 2019/8
Y1 - 2019/8
N2 - Background & Aims: The clinical efficacy of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) remains subject to debate as definitive randomized controlled trials are lacking. We aimed to determine whether UDCA prolongs liver transplant (LT)-free survival in patients with PBC. Methods: This international cohort study included patients from the Global PBC Study Group database, originating from 8 countries in Europe and North America. Both UDCA-treated and untreated patients were included. LT and death were assessed as a combined endpoint through Cox regression analyses, with inverse probability treatment weighting (IPTW). Results: In the 3,902 patients included, the mean (SD) age was 54.3 (11.9) years, 3,552 patients (94.0%) were female, 3,529 patients (90.4%) were treated with UDCA and 373 patients (9.6%) were not treated. The median (interquartile range) follow-up was 7.8 (4.1–12.1) years. In total, 721 UDCA-treated patients and 145 untreated patients died or underwent LT. After IPTW, the 10-year cumulative LT-free survival was 79.7% (95% CI 78.1–81.2) among UDCA-treated patients and 60.7% (95% CI 58.2–63.4) among untreated patients (p <0.001). UDCA was associated with a statistically significant reduced risk of LT or death (hazard ratio 0.46, 95% CI 0.40–0.52; p <0.001). The hazard ratio remained statistically significant in all stages of disease. Patients classified as inadequate biochemical responders after 1 year of UDCA had a lower risk of LT or death than patients who were not treated (adjusted hazard ratio 0.56; 95% CI 0.45–0.69; p <0.001). Conclusion: The use of UDCA improves LT-free survival among patients with PBC, regardless of the disease stage and the observed biochemical response. These findings support UDCA as the current universal standard of care in PBC. Lay summary: In this international multicenter study of 3,902 patients with primary biliary cholangitis, we found that treatment with ursodeoxycholic acid is associated with prolonged liver transplant-free survival. This association was significant, irrespective of sex, age, or disease stage. The survival benefit remained statistically significant in patients with an incomplete biochemical response to ursodeoxycholic acid therapy.
AB - Background & Aims: The clinical efficacy of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) remains subject to debate as definitive randomized controlled trials are lacking. We aimed to determine whether UDCA prolongs liver transplant (LT)-free survival in patients with PBC. Methods: This international cohort study included patients from the Global PBC Study Group database, originating from 8 countries in Europe and North America. Both UDCA-treated and untreated patients were included. LT and death were assessed as a combined endpoint through Cox regression analyses, with inverse probability treatment weighting (IPTW). Results: In the 3,902 patients included, the mean (SD) age was 54.3 (11.9) years, 3,552 patients (94.0%) were female, 3,529 patients (90.4%) were treated with UDCA and 373 patients (9.6%) were not treated. The median (interquartile range) follow-up was 7.8 (4.1–12.1) years. In total, 721 UDCA-treated patients and 145 untreated patients died or underwent LT. After IPTW, the 10-year cumulative LT-free survival was 79.7% (95% CI 78.1–81.2) among UDCA-treated patients and 60.7% (95% CI 58.2–63.4) among untreated patients (p <0.001). UDCA was associated with a statistically significant reduced risk of LT or death (hazard ratio 0.46, 95% CI 0.40–0.52; p <0.001). The hazard ratio remained statistically significant in all stages of disease. Patients classified as inadequate biochemical responders after 1 year of UDCA had a lower risk of LT or death than patients who were not treated (adjusted hazard ratio 0.56; 95% CI 0.45–0.69; p <0.001). Conclusion: The use of UDCA improves LT-free survival among patients with PBC, regardless of the disease stage and the observed biochemical response. These findings support UDCA as the current universal standard of care in PBC. Lay summary: In this international multicenter study of 3,902 patients with primary biliary cholangitis, we found that treatment with ursodeoxycholic acid is associated with prolonged liver transplant-free survival. This association was significant, irrespective of sex, age, or disease stage. The survival benefit remained statistically significant in patients with an incomplete biochemical response to ursodeoxycholic acid therapy.
KW - Cholestasis
KW - Clinical trials
KW - Mortality
KW - Patient management
KW - Treatment
KW - UDCA, transplantation
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U2 - 10.1016/j.jhep.2019.04.001
DO - 10.1016/j.jhep.2019.04.001
M3 - Article
C2 - 30980847
AN - SCOPUS:85066080497
SN - 0168-8278
VL - 71
SP - 357
EP - 365
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 2
ER -