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A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis

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A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis. / Kowdley, Kris V; Luketic, Velimir; Chapman, Roger; Hirschfield, Gideon M; Poupon, Raoul; Schramm, Christoph; Vincent, Catherine; Rust, Christian; Parés, Albert; Mason, Andrew; Marschall, Hanns-Ulrich; Shapiro, David; Adorini, Luciano; Sciacca, Cathi; Beecher-Jones, Tessa; Böhm, Olaf; Pencek, Richard; Jones, David; Obeticholic Acid PBC Monotherapy Study Group.

In: HEPATOLOGY, Vol. 67, No. 5, 05.2018, p. 1890-1902.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Kowdley, KV, Luketic, V, Chapman, R, Hirschfield, GM, Poupon, R, Schramm, C, Vincent, C, Rust, C, Parés, A, Mason, A, Marschall, H-U, Shapiro, D, Adorini, L, Sciacca, C, Beecher-Jones, T, Böhm, O, Pencek, R, Jones, D & Obeticholic Acid PBC Monotherapy Study Group 2018, 'A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis', HEPATOLOGY, vol. 67, no. 5, pp. 1890-1902. https://doi.org/10.1002/hep.29569

APA

Kowdley, K. V., Luketic, V., Chapman, R., Hirschfield, G. M., Poupon, R., Schramm, C., Vincent, C., Rust, C., Parés, A., Mason, A., Marschall, H-U., Shapiro, D., Adorini, L., Sciacca, C., Beecher-Jones, T., Böhm, O., Pencek, R., Jones, D., & Obeticholic Acid PBC Monotherapy Study Group (2018). A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis. HEPATOLOGY, 67(5), 1890-1902. https://doi.org/10.1002/hep.29569

Vancouver

Kowdley KV, Luketic V, Chapman R, Hirschfield GM, Poupon R, Schramm C et al. A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis. HEPATOLOGY. 2018 May;67(5):1890-1902. https://doi.org/10.1002/hep.29569

Bibtex

@article{e11f8f2af7234b1fadb8f9b9d258e3f5,
title = "A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis",
abstract = "Obeticholic acid (OCA), a potent farnesoid X receptor agonist, was studied as monotherapy in an international, randomized, double-blind, placebo-controlled phase 2 study in patients with primary biliary cholangitis who were then followed for up to 6 years. The goals of the study were to assess the benefit of OCA in the absence of ursodeoxycholic acid, which is relevant for patients who are intolerant of ursodeoxycholic acid and at higher risk of disease progression. Patients were randomized and dosed with placebo (n = 23), OCA 10 mg (n = 20), or OCA 50 mg (n = 16) given as monotherapy once daily for 3 months (1 randomized patient withdrew prior to dosing). The primary endpoint was the percent change in alkaline phosphatase from baseline to the end of the double-blind phase of the study. Secondary and exploratory endpoints included change from baseline to month 3/early termination in markers of cholestasis, hepatocellular injury, and farnesoid X receptor activation. Efficacy and safety continue to be monitored through an ongoing 6-year open-label extension (N = 28). Alkaline phosphatase was reduced in both OCA groups (median% [Q1, Q3], OCA 10 mg -53.9% [-62.5, -29.3], OCA 50 mg -37.2% [-54.8, -24.6]) compared to placebo (-0.8% [-6.4, 8.7]; P < 0.0001) at the end of the study, with similar reductions observed through 6 years of open-label extension treatment. OCA improved many secondary and exploratory endpoints (including γ-glutamyl transpeptidase, alanine aminotransferase, conjugated bilirubin, and immunoglobulin M). Pruritus was the most common adverse event; 15% (OCA 10 mg) and 38% (OCA 50 mg) discontinued due to pruritus.CONCLUSION: OCA monotherapy significantly improved alkaline phosphatase and other biochemical markers predictive of improved long-term clinical outcomes. Pruritus increased dose-dependently with OCA treatment. Biochemical improvements were observed through 6 years of open-label extension treatment. (Hepatology 2018;67:1890-1902).",
keywords = "Journal Article",
author = "Kowdley, {Kris V} and Velimir Luketic and Roger Chapman and Hirschfield, {Gideon M} and Raoul Poupon and Christoph Schramm and Catherine Vincent and Christian Rust and Albert Par{\'e}s and Andrew Mason and Hanns-Ulrich Marschall and David Shapiro and Luciano Adorini and Cathi Sciacca and Tessa Beecher-Jones and Olaf B{\"o}hm and Richard Pencek and David Jones and {Obeticholic Acid PBC Monotherapy Study Group}",
note = "{\textcopyright} 2017 The Authors. Hepatology published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.",
year = "2018",
month = may,
doi = "10.1002/hep.29569",
language = "English",
volume = "67",
pages = "1890--1902",
journal = "HEPATOLOGY",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "5",

}

RIS

TY - JOUR

T1 - A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis

AU - Kowdley, Kris V

AU - Luketic, Velimir

AU - Chapman, Roger

AU - Hirschfield, Gideon M

AU - Poupon, Raoul

AU - Schramm, Christoph

AU - Vincent, Catherine

AU - Rust, Christian

AU - Parés, Albert

AU - Mason, Andrew

AU - Marschall, Hanns-Ulrich

AU - Shapiro, David

AU - Adorini, Luciano

AU - Sciacca, Cathi

AU - Beecher-Jones, Tessa

AU - Böhm, Olaf

AU - Pencek, Richard

AU - Jones, David

AU - Obeticholic Acid PBC Monotherapy Study Group

N1 - © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.

PY - 2018/5

Y1 - 2018/5

N2 - Obeticholic acid (OCA), a potent farnesoid X receptor agonist, was studied as monotherapy in an international, randomized, double-blind, placebo-controlled phase 2 study in patients with primary biliary cholangitis who were then followed for up to 6 years. The goals of the study were to assess the benefit of OCA in the absence of ursodeoxycholic acid, which is relevant for patients who are intolerant of ursodeoxycholic acid and at higher risk of disease progression. Patients were randomized and dosed with placebo (n = 23), OCA 10 mg (n = 20), or OCA 50 mg (n = 16) given as monotherapy once daily for 3 months (1 randomized patient withdrew prior to dosing). The primary endpoint was the percent change in alkaline phosphatase from baseline to the end of the double-blind phase of the study. Secondary and exploratory endpoints included change from baseline to month 3/early termination in markers of cholestasis, hepatocellular injury, and farnesoid X receptor activation. Efficacy and safety continue to be monitored through an ongoing 6-year open-label extension (N = 28). Alkaline phosphatase was reduced in both OCA groups (median% [Q1, Q3], OCA 10 mg -53.9% [-62.5, -29.3], OCA 50 mg -37.2% [-54.8, -24.6]) compared to placebo (-0.8% [-6.4, 8.7]; P < 0.0001) at the end of the study, with similar reductions observed through 6 years of open-label extension treatment. OCA improved many secondary and exploratory endpoints (including γ-glutamyl transpeptidase, alanine aminotransferase, conjugated bilirubin, and immunoglobulin M). Pruritus was the most common adverse event; 15% (OCA 10 mg) and 38% (OCA 50 mg) discontinued due to pruritus.CONCLUSION: OCA monotherapy significantly improved alkaline phosphatase and other biochemical markers predictive of improved long-term clinical outcomes. Pruritus increased dose-dependently with OCA treatment. Biochemical improvements were observed through 6 years of open-label extension treatment. (Hepatology 2018;67:1890-1902).

AB - Obeticholic acid (OCA), a potent farnesoid X receptor agonist, was studied as monotherapy in an international, randomized, double-blind, placebo-controlled phase 2 study in patients with primary biliary cholangitis who were then followed for up to 6 years. The goals of the study were to assess the benefit of OCA in the absence of ursodeoxycholic acid, which is relevant for patients who are intolerant of ursodeoxycholic acid and at higher risk of disease progression. Patients were randomized and dosed with placebo (n = 23), OCA 10 mg (n = 20), or OCA 50 mg (n = 16) given as monotherapy once daily for 3 months (1 randomized patient withdrew prior to dosing). The primary endpoint was the percent change in alkaline phosphatase from baseline to the end of the double-blind phase of the study. Secondary and exploratory endpoints included change from baseline to month 3/early termination in markers of cholestasis, hepatocellular injury, and farnesoid X receptor activation. Efficacy and safety continue to be monitored through an ongoing 6-year open-label extension (N = 28). Alkaline phosphatase was reduced in both OCA groups (median% [Q1, Q3], OCA 10 mg -53.9% [-62.5, -29.3], OCA 50 mg -37.2% [-54.8, -24.6]) compared to placebo (-0.8% [-6.4, 8.7]; P < 0.0001) at the end of the study, with similar reductions observed through 6 years of open-label extension treatment. OCA improved many secondary and exploratory endpoints (including γ-glutamyl transpeptidase, alanine aminotransferase, conjugated bilirubin, and immunoglobulin M). Pruritus was the most common adverse event; 15% (OCA 10 mg) and 38% (OCA 50 mg) discontinued due to pruritus.CONCLUSION: OCA monotherapy significantly improved alkaline phosphatase and other biochemical markers predictive of improved long-term clinical outcomes. Pruritus increased dose-dependently with OCA treatment. Biochemical improvements were observed through 6 years of open-label extension treatment. (Hepatology 2018;67:1890-1902).

KW - Journal Article

U2 - 10.1002/hep.29569

DO - 10.1002/hep.29569

M3 - SCORING: Journal article

C2 - 29023915

VL - 67

SP - 1890

EP - 1902

JO - HEPATOLOGY

JF - HEPATOLOGY

SN - 0270-9139

IS - 5

ER -