Efficacy and Safety of Biologics in Primary Biliary Cholangitis: A Systematic Review of Experimental Treatments

Abstract

Background: Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disease characterised by progressive bile duct destruction, leading to liver failure if untreated. While ursodeoxycholic acid (UDCA) is the first-line therapy for PBC, 30-40% of patients exhibit an incomplete response. For these patients, biologic therapies targeting specific immune pathways offer promising alternatives. This systematic review evaluates the efficacy and safety of biologic treatments in PBC, focusing on improvements in liver function, disease progression, symptom relief, and adverse events. Methods: Adhering to PRISMA 2020 guidelines, a comprehensive search of PubMed, Embase, Cochrane Library, Web of Science, and Scopus was conducted to identify studies evaluating biologic therapies in PBC. Studies published in the last 15 years were included, focusing on experimental treatments compared to standard care or placebo. Both randomised controlled trials (RCTs) and observational studies were considered. Data extraction focused on study design, population characteristics, treatment outcomes, and safety profiles. Results: Seven studies, including 9,590 participants, were reviewed, focusing on the efficacy and safety of biologic therapies in PBC. The majority of patients were women, aged 18 to 75, who had an incomplete response to UDCA. Obeticholic acid (OCA) was assessed in multiple studies, with an RCT showing no significant difference in the primary endpoint (HR 1.01, 95% CI 0.68–1.51) compared to placebo. However, external control analysis showed a significant reduction in liver-related events (HR 0.39, p=0.0010). Seladelpar demonstrated a significant reduction in ALP levels, with 78.2% of patients achieving a biochemical response (p<0.0001) and 27.3% normalising ALP. It also reduced pruritus (p=0.02). Adverse events included high rates of pruritus in OCA-treated patients (78.6%), leading to treatment discontinuation in 30.6% of cases. Seladelpar had fewer side effects but still reported mild issues like abdominal pain and pruritus. Conclusion: Biologic therapies show potential in improving PBC outcomes, but safety concerns, particularly related to adverse events, must be carefully managed. Future research should explore long-term efficacy and safety to better refine treatment strategies for PBC.