Beyond Ursodeoxycholic Acid: A Comprehensive Review of Second-Line Agents in Primary Biliary Cholangitis

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterised by progressive bile duct injury and cholestasis. It predominantly affects middle-aged women and typically presents with symptoms such as fatigue, pruritus, and deranged liver enzymes. While ursodeoxycholic acid (UDCA) remains the first-line therapy, a significant proportion of patients fail to achieve adequate biochemical response, leaving them vulnerable to disease progression. Until recently, treatment options for these individuals in the United Kingdom (UK) were limited. However, the therapeutic landscape is evolving with the recent approval of elafibranor and seladelpar, offering new hope for patients and clinicians alike. This review highlights key characteristics of these emerging second-line agents, including their mechanisms of action, administration, safety profiles, and regulatory status in the UK. Special attention is given to the clinical implications of their approval and accessibility within NHS pathways. In addition to disease-modifying therapies, adjunctive strategies for symptom control, particularly for pruritus and fatigue, are also discussed, along with a brief overview of future therapeutic directions. By summarising the expanding treatment arsenal, this review aims to support evidence-informed decision-making and promote timely specialist referral in patients with suboptimal response to UDCA.