Efficacy and Safety of Biologics in Primary Biliary Cholangitis: A Systematic Review of Experimental Treatments
Tobechukwu Chinenye Ezike *
College of Public Health, East Tennessee State University, USA.
Tania M. Cobena Bravo
American University of Antigua College of Medicine, Antigua & Barbuda.
Roshan Goswami
American University of Antigua College of Medicine, Antigua & Barbuda.
Luis Fernando Jimenez Cepeda
Universidad Libre Seccional Barranquilla, Colombia.
Huma Irfan
Isra University, Pakistan.
Tagbo Ejike Onyemelukwe
American University of Barbados School of Medicine, Barbados.
Maryfortune Ugoeze Chilaka
Chukwuemeka Odumegwu Ojukwu University College of Medical Sciences, Nigeria.
Ibiai Stephanie Lolomari
American University of Barbados School of Medicine, Barbados.
Vimla Devi
People’s Medical College, Pakistan.
Sefiyah Lawal
American University of Barbados School of Medicine, Barbados.
Chukwuma Chuma-Eze
American University of Barbados School of Medicine, Barbados.
Oluwatobi Bamikole Opeyemi
Zaporizhzhia State Medical University, Ukraine.
Shwetha Gopal
Davao Medical School Foundation, Philippines.
Agho Osamede
Oba Okunade College of Health Sciences, Igbinedion University, Nigeria.
Peace Divine Akhimienmhona
Kharkiv National University V.N.Karazin, Ukraine.
*Author to whom correspondence should be addressed.
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.
Keywords: Primary biliary cholangitis, biologics, ursodeoxycholic acid, obeticholic acid, seladelpar, autoimmune liver disease, adverse events