Considerations for Treatment Sequencing in Primary Biliary Cholangitis

In recognition of the US Food and Drug Administration accelerated approval of Gilead's seladelpar (Livdelzi) and other recent evolutions in primary biliary cholangitis (PBC), the latest HCPLive Special Report spotlights a conversation between a trio of subject matter experts on the latest advancements in PBC and their implications for disease management.

A chronic and progressive autoimmune liver disease affecting intrahepatic bile ducts, common symptoms of PBC include ​​jaundice, pruritus, and fatigue. Ursodeoxycholic acid (UDCA) has long been the mainstay of treatment for PBC and continues to be the only first-line therapy. However, many patients do not respond to or are unable to tolerate UDCA, underscoring the need for more treatment options to prevent progression to cirrhosis and eventual liver failure as well as to improve symptoms most negatively impacting patients. In the past 3 months alone, the PBC treatment landscape has seen the addition of 2 new therapeutic options with the accelerated approvals of seladelpar and elafibranor, both of which are proliferator-activated receptor agonists shown to reduce alkaline phosphatase.

In the fourth segment of our 6-part HCPLive Special Report on the evolving landscape of PBC management, moderator Nancy Reau, MD, asks Palak Trivedi, MD, PhD, and Gideon Hirschfield, PhD, MB BChir, about controversies regarding the sequencing of treatments. Hirschfield responds that although he does not think the field is completely certain about sequencing, it has generally included licensed therapies first, and he expects it to continue to change as more choices of licensed therapies become available. As a whole, he expresses excitement about having the choice to sequence therapies in PBC compared to where the field was in 2016.

Trivedi also highlights 3 things he considers when determining sequencing: policy, patient phenotype, and the regulatory pathway leading to market entry. He places particular emphasis on patient phenotype but acknowledges the importance of effectively navigating all 3 for optimizing patient outcomes in PBC management.

Check out the other segments in this series:

• Part 1: Shifting Treatment Goals, Timelines in PBC
• Part 2: Recent Advances in Second-Line Therapies
• Part 3: Assessing PBC Treatment Options, Sequencing
• Part 4: Considerations for Treatment Sequencing in PBC
• Part 5: Impact of Next-Generation PPAR Agonists on PBC Management
• Part 6: The Future of PBC Management, Pipeline Developments

Panelists

• Nancy Reau, MD (Moderator): associate director of solid organ transplantation and section chief of hepatology at Rush University Medical Center
• Palak Trivedi, MD, PhD: associate professor and honorary consultant hepatologist and clinical research director for industry engagement at the University of Birmingham
• Gideon Hirschfield, PhD, MB BChir: director of the Autoimmune Liver Disease Program at University Health Network’s Francis Family Liver Clinic and Toronto Centre for Liver Disease and Lily and Terry Horner Chair in Autoimmune Liver Disease Research at the University of Toronto

Relevant disclosures for Reau include Eiger, Gilead, AbbVie, Salix, and Intercept. Relevant disclosures for Trivedi include Bristol Myers Squibb, Gilead, Intercept, CymbaBay, and others. Relevant disclosures for Hirschfield include CymaBay, Escient, Gilead, GSK, HighTide, Intercept, Ipsen, Mirum, and Pliant.