Efficacy and safety of PPAR agonists in primary biliary cholangitis: a systematic review and meta-analysis of Randomized Controlled Trials
Behrad Saeedian, Nastaran Babajani, Tannaz Bagheri, Fatemeh Ojaghi Shirmard, Seyed Morteza Pourfaraji
Abstract
BACKGROUND AND AIMS: Primary biliary cholangitis (PBC) is a chronic, progressive autoimmune liver disease. Some patients with PBC do not adequately respond to Ursodeoxycholic acid (UDCA) as a first-line treatment, putting them at an increased risk of disease progression. Peroxisome Proliferator-Activated Receptor (PPAR) agonists are emerging as promising therapeutic options for PBC. We aim to investigate the efficacy and safety of PPAR agonists in treating PBC patients. METHODS: PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov were searched for Randomized Controlled Trials (RCTs) investigating the use of PPAR agonists in combination with UDCA in patients with PBC, compared to UDCA alone. Mean differences (MD) for continuous variables and risk ratios (RR) for dichotomous variables were calculated to compare treatment response endpoints. RESULTS: A total of 17 studies with 1219 PBC cases were included in the current review. Alkaline phosphatase (ALP) levels had a significantly greater decline in PPAR and UDCA arms than in UDCA alone (MD - 131.15, 95% CI - 155.95 to - 106.36). Furthermore, in combination therapy arms, gamma-glutamyl transferase (GGT) (MD - 55.69, 95% CI - 76.26 to - 35.13) and total bilirubin (MD - 0.08, 95% CI - 0.14 to - 0.03) were significantly lower than in the UDCA alone group. CONCLUSIONS: The current study demonstrates that combining UDCA and PPAR agonists effectively reduces ALP, GGT, and Bilirubin levels, crucial markers for effective therapy in PBC patients.