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A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis.

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A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis. / Nevens, Frederik; Andreone, Pietro; Mazzella, Giuseppe; Strasser, Simone I; Bowlus, Christopher; Invernizzi, Pietro; Drenth, Joost P H; Pockros, Paul J; Regula, Jaroslaw; Beuers, Ulrich; Trauner, Michael; Jones, David E; Floreani, Annarosa; Hohenester, Simon; Luketic, Velimir; Shiffman, Mitchell; van Erpecum, Karel J; Vargas, Victor; Vincent, Catherine; Hirschfield, Gideon M; Shah, Hemant; Hansen, Bettina; Lindor, Keith D; Marschall, Hanns-Ulrich; Kowdley, Kris V; Hooshmand-Rad, Roya; Marmon, Tonya; Sheeron, Shawn; Pencek, Richard; MacConell, Leigh; Pruzanski, Mark; Shapiro, David; POISE Study Group.

in: NEW ENGL J MED, Jahrgang 375, Nr. 7, 18.08.2016, S. 631-43.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Nevens, F, Andreone, P, Mazzella, G, Strasser, SI, Bowlus, C, Invernizzi, P, Drenth, JPH, Pockros, PJ, Regula, J, Beuers, U, Trauner, M, Jones, DE, Floreani, A, Hohenester, S, Luketic, V, Shiffman, M, van Erpecum, KJ, Vargas, V, Vincent, C, Hirschfield, GM, Shah, H, Hansen, B, Lindor, KD, Marschall, H-U, Kowdley, KV, Hooshmand-Rad, R, Marmon, T, Sheeron, S, Pencek, R, MacConell, L, Pruzanski, M, Shapiro, D & POISE Study Group 2016, 'A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis.', NEW ENGL J MED, Jg. 375, Nr. 7, S. 631-43. https://doi.org/10.1056/NEJMoa1509840

APA

Nevens, F., Andreone, P., Mazzella, G., Strasser, S. I., Bowlus, C., Invernizzi, P., Drenth, J. P. H., Pockros, P. J., Regula, J., Beuers, U., Trauner, M., Jones, D. E., Floreani, A., Hohenester, S., Luketic, V., Shiffman, M., van Erpecum, K. J., Vargas, V., Vincent, C., ... POISE Study Group (2016). A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis. NEW ENGL J MED, 375(7), 631-43. https://doi.org/10.1056/NEJMoa1509840

Vancouver

Nevens F, Andreone P, Mazzella G, Strasser SI, Bowlus C, Invernizzi P et al. A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis. NEW ENGL J MED. 2016 Aug 18;375(7):631-43. https://doi.org/10.1056/NEJMoa1509840

Bibtex

@article{8c2d4836ec564783ae4e059354200120,
title = "A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis.",
abstract = "BACKGROUND: Primary biliary cholangitis (formerly called primary biliary cirrhosis) can progress to cirrhosis and death despite ursodiol therapy. Alkaline phosphatase and bilirubin levels correlate with the risk of liver transplantation or death. Obeticholic acid, a farnesoid X receptor agonist, has shown potential benefit in patients with this disease.METHODS: In this 12-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 217 patients who had an inadequate response to ursodiol or who found the side effects of ursodiol unacceptable to receive obeticholic acid at a dose of 10 mg (the 10-mg group), obeticholic acid at a dose of 5 mg with adjustment to 10 mg if applicable (the 5-10-mg group), or placebo. The primary end point was an alkaline phosphatase level of less than 1.67 times the upper limit of the normal range, with a reduction of at least 15% from baseline, and a normal total bilirubin level.RESULTS: Of 216 patients who underwent randomization and received at least one dose of obeticholic acid or placebo, 93% received ursodiol as background therapy. The primary end point occurred in more patients in the 5-10-mg group (46%) and the 10-mg group (47%) than in the placebo group (10%; P<0.001 for both comparisons). Patients in the 5-10-mg group and those in the 10-mg group had greater decreases than those in the placebo group in the alkaline phosphatase level (least-squares mean, -113 and -130 U per liter, respectively, vs. -14 U per liter; P<0.001 for both comparisons) and total bilirubin level (-0.02 and -0.05 mg per deciliter [-0.3 and -0.9 μmol per liter], respectively, vs. 0.12 mg per deciliter [2.0 μmol per liter]; P<0.001 for both comparisons). Changes in noninvasive measures of liver fibrosis did not differ significantly between either treatment group and the placebo group at 12 months. Pruritus was more common with obeticholic acid than with placebo (56% of patients in the 5-10-mg group and 68% of those in the 10-mg group vs. 38% in the placebo group). The rate of serious adverse events was 16% in the 5-10-mg group, 11% in the 10-mg group, and 4% in the placebo group.CONCLUSIONS: Obeticholic acid administered with ursodiol or as monotherapy for 12 months in patients with primary biliary cholangitis resulted in decreases from baseline in alkaline phosphatase and total bilirubin levels that differed significantly from the changes observed with placebo. There were more serious adverse events with obeticholic acid. (Funded by Intercept Pharmaceuticals; POISE ClinicalTrials.gov number, NCT01473524; Current Controlled Trials number, ISRCTN89514817.).",
keywords = "Adult, Aged, Alkaline Phosphatase, Bile Acids and Salts, Bone Density, Chenodeoxycholic Acid, Double-Blind Method, Female, Fibroblast Growth Factors, Humans, Liver Cirrhosis, Liver Cirrhosis, Biliary, Male, Middle Aged, Pruritus, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't",
author = "Frederik Nevens and Pietro Andreone and Giuseppe Mazzella and Strasser, {Simone I} and Christopher Bowlus and Pietro Invernizzi and Drenth, {Joost P H} and Pockros, {Paul J} and Jaroslaw Regula and Ulrich Beuers and Michael Trauner and Jones, {David E} and Annarosa Floreani and Simon Hohenester and Velimir Luketic and Mitchell Shiffman and {van Erpecum}, {Karel J} and Victor Vargas and Catherine Vincent and Hirschfield, {Gideon M} and Hemant Shah and Bettina Hansen and Lindor, {Keith D} and Hanns-Ulrich Marschall and Kowdley, {Kris V} and Roya Hooshmand-Rad and Tonya Marmon and Shawn Sheeron and Richard Pencek and Leigh MacConell and Mark Pruzanski and David Shapiro and {POISE Study Group}",
year = "2016",
month = aug,
day = "18",
doi = "10.1056/NEJMoa1509840",
language = "English",
volume = "375",
pages = "631--43",
journal = "NEW ENGL J MED",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "7",

}

RIS

TY - JOUR

T1 - A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis.

AU - Nevens, Frederik

AU - Andreone, Pietro

AU - Mazzella, Giuseppe

AU - Strasser, Simone I

AU - Bowlus, Christopher

AU - Invernizzi, Pietro

AU - Drenth, Joost P H

AU - Pockros, Paul J

AU - Regula, Jaroslaw

AU - Beuers, Ulrich

AU - Trauner, Michael

AU - Jones, David E

AU - Floreani, Annarosa

AU - Hohenester, Simon

AU - Luketic, Velimir

AU - Shiffman, Mitchell

AU - van Erpecum, Karel J

AU - Vargas, Victor

AU - Vincent, Catherine

AU - Hirschfield, Gideon M

AU - Shah, Hemant

AU - Hansen, Bettina

AU - Lindor, Keith D

AU - Marschall, Hanns-Ulrich

AU - Kowdley, Kris V

AU - Hooshmand-Rad, Roya

AU - Marmon, Tonya

AU - Sheeron, Shawn

AU - Pencek, Richard

AU - MacConell, Leigh

AU - Pruzanski, Mark

AU - Shapiro, David

AU - POISE Study Group

PY - 2016/8/18

Y1 - 2016/8/18

N2 - BACKGROUND: Primary biliary cholangitis (formerly called primary biliary cirrhosis) can progress to cirrhosis and death despite ursodiol therapy. Alkaline phosphatase and bilirubin levels correlate with the risk of liver transplantation or death. Obeticholic acid, a farnesoid X receptor agonist, has shown potential benefit in patients with this disease.METHODS: In this 12-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 217 patients who had an inadequate response to ursodiol or who found the side effects of ursodiol unacceptable to receive obeticholic acid at a dose of 10 mg (the 10-mg group), obeticholic acid at a dose of 5 mg with adjustment to 10 mg if applicable (the 5-10-mg group), or placebo. The primary end point was an alkaline phosphatase level of less than 1.67 times the upper limit of the normal range, with a reduction of at least 15% from baseline, and a normal total bilirubin level.RESULTS: Of 216 patients who underwent randomization and received at least one dose of obeticholic acid or placebo, 93% received ursodiol as background therapy. The primary end point occurred in more patients in the 5-10-mg group (46%) and the 10-mg group (47%) than in the placebo group (10%; P<0.001 for both comparisons). Patients in the 5-10-mg group and those in the 10-mg group had greater decreases than those in the placebo group in the alkaline phosphatase level (least-squares mean, -113 and -130 U per liter, respectively, vs. -14 U per liter; P<0.001 for both comparisons) and total bilirubin level (-0.02 and -0.05 mg per deciliter [-0.3 and -0.9 μmol per liter], respectively, vs. 0.12 mg per deciliter [2.0 μmol per liter]; P<0.001 for both comparisons). Changes in noninvasive measures of liver fibrosis did not differ significantly between either treatment group and the placebo group at 12 months. Pruritus was more common with obeticholic acid than with placebo (56% of patients in the 5-10-mg group and 68% of those in the 10-mg group vs. 38% in the placebo group). The rate of serious adverse events was 16% in the 5-10-mg group, 11% in the 10-mg group, and 4% in the placebo group.CONCLUSIONS: Obeticholic acid administered with ursodiol or as monotherapy for 12 months in patients with primary biliary cholangitis resulted in decreases from baseline in alkaline phosphatase and total bilirubin levels that differed significantly from the changes observed with placebo. There were more serious adverse events with obeticholic acid. (Funded by Intercept Pharmaceuticals; POISE ClinicalTrials.gov number, NCT01473524; Current Controlled Trials number, ISRCTN89514817.).

AB - BACKGROUND: Primary biliary cholangitis (formerly called primary biliary cirrhosis) can progress to cirrhosis and death despite ursodiol therapy. Alkaline phosphatase and bilirubin levels correlate with the risk of liver transplantation or death. Obeticholic acid, a farnesoid X receptor agonist, has shown potential benefit in patients with this disease.METHODS: In this 12-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 217 patients who had an inadequate response to ursodiol or who found the side effects of ursodiol unacceptable to receive obeticholic acid at a dose of 10 mg (the 10-mg group), obeticholic acid at a dose of 5 mg with adjustment to 10 mg if applicable (the 5-10-mg group), or placebo. The primary end point was an alkaline phosphatase level of less than 1.67 times the upper limit of the normal range, with a reduction of at least 15% from baseline, and a normal total bilirubin level.RESULTS: Of 216 patients who underwent randomization and received at least one dose of obeticholic acid or placebo, 93% received ursodiol as background therapy. The primary end point occurred in more patients in the 5-10-mg group (46%) and the 10-mg group (47%) than in the placebo group (10%; P<0.001 for both comparisons). Patients in the 5-10-mg group and those in the 10-mg group had greater decreases than those in the placebo group in the alkaline phosphatase level (least-squares mean, -113 and -130 U per liter, respectively, vs. -14 U per liter; P<0.001 for both comparisons) and total bilirubin level (-0.02 and -0.05 mg per deciliter [-0.3 and -0.9 μmol per liter], respectively, vs. 0.12 mg per deciliter [2.0 μmol per liter]; P<0.001 for both comparisons). Changes in noninvasive measures of liver fibrosis did not differ significantly between either treatment group and the placebo group at 12 months. Pruritus was more common with obeticholic acid than with placebo (56% of patients in the 5-10-mg group and 68% of those in the 10-mg group vs. 38% in the placebo group). The rate of serious adverse events was 16% in the 5-10-mg group, 11% in the 10-mg group, and 4% in the placebo group.CONCLUSIONS: Obeticholic acid administered with ursodiol or as monotherapy for 12 months in patients with primary biliary cholangitis resulted in decreases from baseline in alkaline phosphatase and total bilirubin levels that differed significantly from the changes observed with placebo. There were more serious adverse events with obeticholic acid. (Funded by Intercept Pharmaceuticals; POISE ClinicalTrials.gov number, NCT01473524; Current Controlled Trials number, ISRCTN89514817.).

KW - Adult

KW - Aged

KW - Alkaline Phosphatase

KW - Bile Acids and Salts

KW - Bone Density

KW - Chenodeoxycholic Acid

KW - Double-Blind Method

KW - Female

KW - Fibroblast Growth Factors

KW - Humans

KW - Liver Cirrhosis

KW - Liver Cirrhosis, Biliary

KW - Male

KW - Middle Aged

KW - Pruritus

KW - Clinical Trial, Phase III

KW - Journal Article

KW - Multicenter Study

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.1056/NEJMoa1509840

DO - 10.1056/NEJMoa1509840

M3 - SCORING: Journal article

C2 - 27532829

VL - 375

SP - 631

EP - 643

JO - NEW ENGL J MED

JF - NEW ENGL J MED

SN - 0028-4793

IS - 7

ER -