PARIS — budesonide add-on therapy to ursodeoxycholic acid did not significantly improve histology in high-risk patients with primary biliary cholangitis, the combination showed meaningful improvements in biochemical markers of disease activity, according to a presentation at the International Liver Congress 2018.
“We have very clear guidelines now from EASL about the management of PBC, for which the goals of treatment are to prevent end-stage liver disease and to manage associated symptoms.” Gideon M. Hirschfield, MD, PhD, from the Centre for Liver Research, University of Birmingham, said in his presentation. “We are interested to understand the role of a therapy such as budesonide for those patients with inflammatory phenotypes of PBC, features of autoimmune hepatitis, and inadequate response to current therapies.”
To evaluate the impact of treating patients with Budenofalk (budesonide, Falk) with UDCA after inadequate response to UDCA, Hirschfield and colleagues randomly assigned 62 patients with comparable baseline data to receive either budesonide or placebo for 36 weeks. Twenty-nine patients completed 3 years of treatment.
“For our primary efficacy endpoint the improvement in liver histology we looked at the rates of improvement with respect to inflammation and no progression,” Hirschfield sad “At last observation, we did not meet the primary endpoint.”
However, Hirschfield and colleagues observed a significant proportion of treated patients who achieved serum alkaline phosphatase of 1.67 or less than the upper limit of normal and a 15% decrease in alkaline phosphatase from baseline with normal bilirubin compared with placebo at 12 months (40% vs. 18%; P = .029), 24 months (45% vs. 18%; P = .021), and 36 months (43% vs. 23%; P = .038).
Reported adverse events were similar between the treated group and the placebo group.
“Clinical research to improve the therapeutic options available for primary biliary cholangitis is key, and studies such as these are important to help understand the measures need to individualize treatment protocols by identifying the hallmark clinical features of response,” Marco Marzioni, MD, from the University Hospital of Ancona in Italy and EASL Governing Board Member, said in a press release. “This study also highlights the complexity of research focusing on cholangiopathies, and how this is impacted by the small pool of patients that are eligble to enter clinical trials. Yet, hepatologists do not leave those patients behind, and continue to work on developing more effective clinical management options.”
For more information:
Hirschfield G, et al. Abstract GS-011. Presented at: International Liver Congress; Apr. 11-15, 2018; Paris, France.
Disclosure: Hirschfield reports he has consulted for Cymabay, GlaxoSmithKline, Intercept and Novartis; served on the speakers bureau for Falk and Intercept; and received unrestricted grants from Falk and Gilead.
Editor’s note: This item has been updated with clarifications from the presenter.