MedicalResearch.com Interview with:
Prof. Dr. F. Nevens, MD, PhD
Professor of Medicine
Hepatology and liver transplantation
University Hospitals KU Leuven, Belgium
MedicalResearch.com: What is the background for this study?
Response: Primary biliary cholangitis (PBC) is a rare, autoimmune cholestatic liver disease that puts patients at risk for life-threatening complications. PBC is primarily a disease of women, affecting approximately one in 1,000 women over the age of 40. If left untreated, survival of PBC patients is significantly worse than the general population.
The POISE trial evaluated the safety and efficacy of once-daily treatment with Ocaliva® (obeticholic acid) in PBC patients with an inadequate therapeutic response to, or who are unable to tolerate, ursodeoxycholic acid (UDCA), the current standard of care. Ocaliva is the first PBC therapy that targets the farnesoid X receptor (FXR), a key regulator of bile acid, inflammatory, fibrotic and metabolic pathways.
The trial’s primary endpoint was an alkaline phosphatase (ALP) 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 total bilirubin level at or below the upper limit of the normal range after 12 months of obeticholic acid therapy. These liver biomarkers have been shown to predict progression to liver failure and resulting liver transplant or premature death in patients with PBC.
MedicalResearch.com: What are the main findings?
Response: In POISE, 216 patients were randomized to three treatment arms—placebo, Ocaliva 5 mg titrated to 10 mg or Ocaliva 10 mg. The Ocaliva 5-10 mg titration group received Ocaliva 5 mg for six months, after which dosing was increased to 10 mg based on tolerability and biochemical response. Ocaliva 5-10 mg (46%) and Ocaliva 10 mg (47%) were both statistically superior to placebo (10%) in achieving the primary endpoint (p<0.001). The majority of patients (93%) continued receiving UDCA therapy during the trial.
A large majority (97%) of the patients who completed the double-blind phase entered an open-label extension. Patients who had received Ocaliva in the double-blind phase experienced sustained improvements in ALP and bilirubin, demonstrating a durable response through 2 years of treatment. Placebo patients initiating treatment with Ocaliva in the open-label extension demonstrated similar efficacy to the Ocaliva-treated patients in the double-blind phase, including reversal of previous increases in total bilirubin to levels comparable to baseline.
MedicalResearch.com: What should readers take away from your report?
Response: The POISE data support Ocaliva as a treatment option for the substantial group of Primary biliary cholangitis patients who have an inadequate response to, or cannot tolerate, UDCA and therefore remain at risk of adverse outcomes.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Obeticholic acid is an FXR agonist that has potential across a variety of non-viral liver diseases in addition to PBC. The therapy is also being evaluated for potential indications in nonalcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC), and biliary atresia.
MedicalResearch.com: Is there anything else you would like to add?
Response: For nearly 20 years, physicians have only had one option to help our PBC patients. The approval of Ocaliva in the U.S., supported by the data in POISE, provides physicians and patients with an opportunity to rethink treatment goals and take action when ALP and/or bilirubin remain elevated despite UDCA therapy.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis
Frederik Nevens, M.D., Ph.D., Pietro Andreone, M.D., Giuseppe Mazzella, M.D., Simone I. Strasser, M.B., B.S., M.D., Christopher Bowlus, M.D., Pietro Invernizzi, M.D., Ph.D., Joost P.H. Drenth, M.D., Ph.D., Paul J. Pockros, M.D., Jaroslaw Regula, M.D., Ph.D., Ulrich Beuers, M.D., Michael Trauner, M.D., David E. Jones, M.B., B.Chir., Ph.D., Annarosa Floreani, M.D., Simon Hohenester, M.D., Velimir Luketic, M.D., Mitchell Shiffman, M.D., Karel J. van Erpecum, M.D., Ph.D., Victor Vargas, M.D., Catherine Vincent, M.D., Gideon M. Hirschfield, M.B., B.Chir., Ph.D., Hemant Shah, M.D., M.Sc.C.H., H.P.T.E., Bettina Hansen, Ph.D., Keith D. Lindor, M.D., Hanns-Ulrich Marschall, M.D., Ph.D., Kris V. Kowdley, M.D., Roya Hooshmand-Rad, M.D., Ph.D., Tonya Marmon, Dr.P.H., Shawn Sheeron, B.S.N., M.B.A., Richard Pencek, Ph.D., Leigh MacConell, Ph.D., Mark Pruzanski, M.D., and David Shapiro, M.B., Ch.B., for the POISE Study Group*
N Engl J Med 2016; 375:631-643August 18, 2016DOI: 10.1056/NEJMoa150984
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