Investigational drugs in phase II clinical trials for primary biliary cholangitis

Marina G. Silveira, Keith Lindor

Research output: Contribution to journalReview article

2 Citations (Scopus)

Abstract

Introduction: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that may lead to biliary fibrosis, and eventually cirrhosis. The primary treatment for PBC is ursodeoxycholic acid (UDCA), which has favorably altered its natural history. However, up to 40% of patients have an inadequate response to UDCA, and are therefore at high risk of liver-related complications. Obeticholic acid has recently been approved for use in patients with PBC with inadequate response or who are intolerant to UDCA, but improvement in long-term outcomes has not yet been demonstrated. Alternative therapeutic options for PBC are needed. Areas covered: Recent advances in research including epidemiological, genetic and pre-clinical studies in animal models of PBC have yielded numerous agents currently at different stages of development for treatment of patients with PBC; in this review, we cover novel therapies that were recently or are recently being investigated in phase II clinical trials. Expert opinion: Despite the evolving landscape in PBC, the main challenges facing development of novel therapies remain the rarity of the disease and the limitations to design and conduct of controlled clinical trials in PBC, which are needed to determine the long-term effects of novel therapies on the clinical outcomes of PBC.

Original languageEnglish (US)
Pages (from-to)1115-1121
Number of pages7
JournalExpert Opinion on Investigational Drugs
Volume26
Issue number10
DOIs
StatePublished - Oct 3 2017

Fingerprint

Investigational Drugs
Phase II Clinical Trials
Cholangitis
Ursodeoxycholic Acid
Fibrosis
Therapeutics
Controlled Clinical Trials
Expert Testimony
Natural History
Liver Diseases
Animal Models

Keywords

  • Autoimmune liver disease
  • bile duct disorders
  • cholestasis
  • pharmacotherapy

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Investigational drugs in phase II clinical trials for primary biliary cholangitis. / Silveira, Marina G.; Lindor, Keith.

In: Expert Opinion on Investigational Drugs, Vol. 26, No. 10, 03.10.2017, p. 1115-1121.

Research output: Contribution to journalReview article

@article{2bb781bf89d6416e973f68493384c9c9,
title = "Investigational drugs in phase II clinical trials for primary biliary cholangitis",
abstract = "Introduction: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that may lead to biliary fibrosis, and eventually cirrhosis. The primary treatment for PBC is ursodeoxycholic acid (UDCA), which has favorably altered its natural history. However, up to 40{\%} of patients have an inadequate response to UDCA, and are therefore at high risk of liver-related complications. Obeticholic acid has recently been approved for use in patients with PBC with inadequate response or who are intolerant to UDCA, but improvement in long-term outcomes has not yet been demonstrated. Alternative therapeutic options for PBC are needed. Areas covered: Recent advances in research including epidemiological, genetic and pre-clinical studies in animal models of PBC have yielded numerous agents currently at different stages of development for treatment of patients with PBC; in this review, we cover novel therapies that were recently or are recently being investigated in phase II clinical trials. Expert opinion: Despite the evolving landscape in PBC, the main challenges facing development of novel therapies remain the rarity of the disease and the limitations to design and conduct of controlled clinical trials in PBC, which are needed to determine the long-term effects of novel therapies on the clinical outcomes of PBC.",
keywords = "Autoimmune liver disease, bile duct disorders, cholestasis, pharmacotherapy",
author = "Silveira, {Marina G.} and Keith Lindor",
year = "2017",
month = "10",
day = "3",
doi = "10.1080/13543784.2017.1371135",
language = "English (US)",
volume = "26",
pages = "1115--1121",
journal = "Expert Opinion on Investigational Drugs",
issn = "1354-3784",
publisher = "Informa Healthcare",
number = "10",

}

TY - JOUR

T1 - Investigational drugs in phase II clinical trials for primary biliary cholangitis

AU - Silveira, Marina G.

AU - Lindor, Keith

PY - 2017/10/3

Y1 - 2017/10/3

N2 - Introduction: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that may lead to biliary fibrosis, and eventually cirrhosis. The primary treatment for PBC is ursodeoxycholic acid (UDCA), which has favorably altered its natural history. However, up to 40% of patients have an inadequate response to UDCA, and are therefore at high risk of liver-related complications. Obeticholic acid has recently been approved for use in patients with PBC with inadequate response or who are intolerant to UDCA, but improvement in long-term outcomes has not yet been demonstrated. Alternative therapeutic options for PBC are needed. Areas covered: Recent advances in research including epidemiological, genetic and pre-clinical studies in animal models of PBC have yielded numerous agents currently at different stages of development for treatment of patients with PBC; in this review, we cover novel therapies that were recently or are recently being investigated in phase II clinical trials. Expert opinion: Despite the evolving landscape in PBC, the main challenges facing development of novel therapies remain the rarity of the disease and the limitations to design and conduct of controlled clinical trials in PBC, which are needed to determine the long-term effects of novel therapies on the clinical outcomes of PBC.

AB - Introduction: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that may lead to biliary fibrosis, and eventually cirrhosis. The primary treatment for PBC is ursodeoxycholic acid (UDCA), which has favorably altered its natural history. However, up to 40% of patients have an inadequate response to UDCA, and are therefore at high risk of liver-related complications. Obeticholic acid has recently been approved for use in patients with PBC with inadequate response or who are intolerant to UDCA, but improvement in long-term outcomes has not yet been demonstrated. Alternative therapeutic options for PBC are needed. Areas covered: Recent advances in research including epidemiological, genetic and pre-clinical studies in animal models of PBC have yielded numerous agents currently at different stages of development for treatment of patients with PBC; in this review, we cover novel therapies that were recently or are recently being investigated in phase II clinical trials. Expert opinion: Despite the evolving landscape in PBC, the main challenges facing development of novel therapies remain the rarity of the disease and the limitations to design and conduct of controlled clinical trials in PBC, which are needed to determine the long-term effects of novel therapies on the clinical outcomes of PBC.

KW - Autoimmune liver disease

KW - bile duct disorders

KW - cholestasis

KW - pharmacotherapy

UR - http://www.scopus.com/inward/record.url?scp=85029221949&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029221949&partnerID=8YFLogxK

U2 - 10.1080/13543784.2017.1371135

DO - 10.1080/13543784.2017.1371135

M3 - Review article

VL - 26

SP - 1115

EP - 1121

JO - Expert Opinion on Investigational Drugs

JF - Expert Opinion on Investigational Drugs

SN - 1354-3784

IS - 10

ER -