Journal article
Long-Term Obeticholic Acid Therapy Improves Histological Endpoints in Patients With Primary Biliary Cholangitis.
- Bowlus CL Division of Gastroenterology and Hepatology, University of California Davis, Sacramento, California. Electronic address: clbowlus@ucdavis.edu.
- Pockros PJ Division of Gastroenterology/Hepatology, Scripps Clinic and Scripps Translational Science Institute, San Diego, La Jolla, California.
- Kremer AE Department of Medicine I, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
- Parés A Hospital Clinic, University of Barcelona, Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas, Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain.
- Forman LM Division of Gastroenterology-Hepatology, University of Colorado, Aurora, Colorado.
- Drenth JPH Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
- Ryder SD National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, United Kingdom.
- Terracciano L Department of Pathology, University of Basel, Basel, Switzerland.
- Jin Y Intercept Pharmaceuticals, San Diego, California.
- Liberman A Intercept Pharmaceuticals, San Diego, California.
- Pencek R Intercept Pharmaceuticals, San Diego, California.
- Iloeje U Intercept Pharmaceuticals, San Diego, California.
- MacConell L Intercept Pharmaceuticals, San Diego, California.
- Bedossa P Department of Pathology, Physiology and Imaging, University Paris Diderot, Paris, France.
- 2019-10-14
Published in:
- Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. - 2020
English
BACKGROUND & AIMS
Primary biliary cholangitis (PBC) is an autoimmune disease characterized by bile duct destruction that can progress to cirrhosis. A liver biopsy substudy was conducted in the PBC obeticholic acid (OCA) International Study of Efficacy (POISE) to determine the long-term effects of OCA on liver damage and fibrosis in patients with PBC. POISE is a phase 3, double-blind, placebo-controlled, randomized trial with a 5-year open-label extension that evaluated 5 to 10 mg OCA daily in patients who were intolerant or unresponsive to ursodeoxycholic acid.
METHODS
Liver biopsy specimens were collected from 17 patients at time of enrollment in the double-blind phase and after 3 years of OCA treatment. Histologic evaluations were performed by 2 pathologists in a blinded, randomized fashion to determine the effects of OCA on fibrosis and other histologic parameters. Collagen morphometry assessments were performed by automated second harmonic generation and 2-photon excitation microscopy to observe quantitative measures of fibrosis.
RESULTS
From the time of enrollment until 3 years of treatment, most patients had improvements or stabilization in fibrosis (71%), bile duct loss (76%), ductopenia (82%), ductular reaction (82%), interface hepatitis (100%), and lobular hepatitis (94%). Over the 3-year period, we found significant reductions in collagen area ratio (median, -2.1; first quartile, -4.6, third quartile, -0.3; P = .013), collagen fiber density (median, -0.8; first quartile, -2.5; third quartile, 0; P = .021), collagen reticulation index (median, -0.1; first quartile, -0.3; third quartile, 0; P = .008), and fibrosis composite score (median, -1.0; first quartile, -2.5; third quartile, -0.5; P = .002).
CONCLUSIONS
A subanalysis of data from the POISE study showed that long-term OCA treatment in patients with PBC is associated with improvements or stabilization of disease features, including ductular injury, fibrosis, and collagen morphometry features (ClinicalTrials.gov no: NCT01473524 and EudraCT no: 2011-004728-36).
Primary biliary cholangitis (PBC) is an autoimmune disease characterized by bile duct destruction that can progress to cirrhosis. A liver biopsy substudy was conducted in the PBC obeticholic acid (OCA) International Study of Efficacy (POISE) to determine the long-term effects of OCA on liver damage and fibrosis in patients with PBC. POISE is a phase 3, double-blind, placebo-controlled, randomized trial with a 5-year open-label extension that evaluated 5 to 10 mg OCA daily in patients who were intolerant or unresponsive to ursodeoxycholic acid.
METHODS
Liver biopsy specimens were collected from 17 patients at time of enrollment in the double-blind phase and after 3 years of OCA treatment. Histologic evaluations were performed by 2 pathologists in a blinded, randomized fashion to determine the effects of OCA on fibrosis and other histologic parameters. Collagen morphometry assessments were performed by automated second harmonic generation and 2-photon excitation microscopy to observe quantitative measures of fibrosis.
RESULTS
From the time of enrollment until 3 years of treatment, most patients had improvements or stabilization in fibrosis (71%), bile duct loss (76%), ductopenia (82%), ductular reaction (82%), interface hepatitis (100%), and lobular hepatitis (94%). Over the 3-year period, we found significant reductions in collagen area ratio (median, -2.1; first quartile, -4.6, third quartile, -0.3; P = .013), collagen fiber density (median, -0.8; first quartile, -2.5; third quartile, 0; P = .021), collagen reticulation index (median, -0.1; first quartile, -0.3; third quartile, 0; P = .008), and fibrosis composite score (median, -1.0; first quartile, -2.5; third quartile, -0.5; P = .002).
CONCLUSIONS
A subanalysis of data from the POISE study showed that long-term OCA treatment in patients with PBC is associated with improvements or stabilization of disease features, including ductular injury, fibrosis, and collagen morphometry features (ClinicalTrials.gov no: NCT01473524 and EudraCT no: 2011-004728-36).
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/j.cgh.2019.09.050
- PMID 31606455
- Persistent URL
- https://sonar.ch/global/documents/160138
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