{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T05:38:28Z","timestamp":1791005908245,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T00:00:00Z","timestamp":1735084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Approximately 40% of patients with Primary Biliary Cholangitis (PBC) show incomplete response to ursodeoxycholic acid, thus needing second\u2010line treatment to prevent disease progression. As no head\u2010to\u2010head comparison study is available, we used a network meta\u2010analysis (NMA) to compare efficacy and safety of available second\u2010line therapies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a systematic literature review including randomised, placebo\u2010controlled trials of patients with PBC and incomplete response, or intolerance, to ursodeoxycholic acid, and compared relative risks (RRs) for primary (biochemical response at 52\u2010week) and secondary outcomes [incidence of new\u2010onset pruritus and serious adverse events (SAEs)].<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The NMA included three studies, each testing obeticholic acid (OCA), seladelpar or elafibranor versus placebo (active therapy\/placebo: 379\/191 patients). All treatments significantly increased the RR for biochemical response with an advantage of elafibranor versus seladelpar (RR: 4.37, 95% CI: 1.01\u201318.87). OCA 5\u201310\u2009mg\/10\u2009mg was associated with a higher risk of new\u2010onset pruritus compared to placebo (RR: 1.43; 95% CI: 1.09\u20131.88\/RR: 1.79; 95% CI: 1.37\u20132.33), while seladelpar decreased this risk (RR: 0.30; 95% CI: 0.12\u20130.80). Compared to placebo, OCA 5\u201310\u2009mg\/10\u2009mg was associated with an increased risk of SAE (RR: 3.82; 95% CI: 1.46\u201310.02\/RR 2.67; 95% CI: 1.00\u20137.08).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Among second line therapies for patients with PBC, elafibranor is slightly more effective in obtaining biochemical response than seladelpar that, on the other hand, is the only drug associated with a lower incidence of pruritus. While of similar efficacy, OCA was associated with increased pruritus and SAEs. These findings may help personalise second\u2010line treatment in patients with PBC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.16222","type":"journal-article","created":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T10:21:56Z","timestamp":1735122116000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Second\u2010Line Treatment for Patients With Primary Biliary Cholangitis: A Systematic Review With Network Meta\u2010Analysis"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8526-837X","authenticated-orcid":false,"given":"Edoardo G.","family":"Giannini","sequence":"first","affiliation":[{"name":"Gastroenterology Unit, Department of Internal Medicine University of Genoa  Genoa Italy"},{"name":"Gastroenterology Unit IRCCS Ospedale Policlinico San Martino  Genoa Italy"},{"name":"Liver Center, Digestive Diseases Section, Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1791-4506","authenticated-orcid":false,"given":"Andrea","family":"Pasta","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Department of Internal Medicine University of Genoa  Genoa Italy"},{"name":"Gastroenterology Unit IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4706-1499","authenticated-orcid":false,"given":"Francesco","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Department of Internal Medicine University of Genoa  Genoa Italy"},{"name":"Gastroenterology Unit IRCCS Ospedale Policlinico San Martino  Genoa 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