{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:25:46Z","timestamp":1784543146759,"version":"3.55.0"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JGH Open"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Peroxisome proliferator\u2010activated receptor (PPAR) agonists are agents used for patients with primary biliary cholangitis (PBC) who do not respond to conventional agents like ursodeoxycholic acid (UDCA). This meta\u2010analysis aimed to assess the safety and efficacy of PPAR agonists, including fibrates and selective PPAR agonists, on biochemical response and safety outcomes in patients with primary biliary cholangitis who were non\u2010responders to UDCA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We searched various electronic databases, including MEDLINE (via PubMed), Embase, the Cochrane Library, and <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>, to retrieve randomized controlled trials (RCTs) comparing PPAR agonists to placebo in patients with PBC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our meta\u2010analysis, including 12 RCTs involving 973 patients, showed that PPAR agonists, including fibrates and selective PPAR agonists, significantly reduce mean alkaline phosphatase (ALP) levels from baseline to follow\u2010up as compared to placebo. They also increase the number of patients with the composite biochemical response (RR 5.51; 95% CI: 2.80, 10.86) and normalize ALP levels with a reduction in pruritus NRS Score and the incidence of pruritus. There was no significant change between the two groups when assessing the mean change in total bilirubin, adverse events, serious adverse events, or mean change in PBC\u201040 score.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In conclusion, our research underscores the potential of novel PPAR agonists in improving biochemical markers in PBC, particularly in patients unresponsive to UDCA. However, further studies with larger sample sizes, longer follow\u2010up durations, and a focus on patient\u2010centered outcomes are necessary. Additionally, exploring combination therapies and mechanistic insights will help us fully realize the therapeutic potential of PPAR agonists in PBC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgh3.70196","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T08:49:17Z","timestamp":1749199757000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Peroxisome Proliferator\u2010Activated Receptor (<scp>PPAR<\/scp>) Agonists for Patients With Primary Biliary Cholangitis With Inadequate Response to Ursodeoxycholic Acid (<scp>UDCA<\/scp>): A Systematic Review and Meta\u2010Analysis of Randomized Controlled Trials"],"prefix":"10.1002","volume":"9","author":[{"given":"Maadeha H.","family":"Zaidi","sequence":"first","affiliation":[{"name":"Department of Medicine Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaroon","family":"Haider","sequence":"additional","affiliation":[{"name":"Department of Medicine CMH Lahore Medical College  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FNU","family":"Sadia","sequence":"additional","affiliation":[{"name":"Department of Medicine Jinnah Sindh Medical University  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Tayyab","sequence":"additional","affiliation":[{"name":"Department of Medicine Faisalabad Medical University  Faisalabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Naveed","family":"Tariq","sequence":"additional","affiliation":[{"name":"Department of Medicine Khyber Medical University  Peshawar Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasaan H.","family":"Ans","sequence":"additional","affiliation":[{"name":"Department of Medicine FMH College of Medicine &amp; 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