{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:47:25Z","timestamp":1789001245983,"version":"build-2803163510"},"reference-count":59,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100006686","name":"University of Miami","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006686","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Pruritus is a frequent and debilitating symptom in primary biliary cholangitis (PBC), substantially impairing sleep, mood and quality of life. Peroxisome proliferator\u2010activated receptor (PPAR) agonists are promising second\u2010line therapies for patients with an inadequate response to ursodeoxycholic acid (UDCA). We conducted a systematic review and meta\u2010analysis to evaluate the efficacy of PPAR agonists on pruritus and health\u2010related quality of life (HRQoL) in PBC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically searched for randomised placebo\u2010controlled trials (RCTs) of PPAR agonists in PBC through December 2025. Eligible studies reported validated pruritus or HRQoL outcomes. Main outcomes were NRS and PBC\u201040 total score. Pooled estimates were calculated using random\u2010effects models and expressed as mean differences (MD) with 95% confidence intervals (CI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Five RCTs evaluating bezafibrate, elafibranor and seladelpar (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009660;\u2009390 PPAR agonist;\u2009270 placebo) met the inclusion criteria. For pruritus intensity analyses, data were restricted to participants with moderate\u2010to\u2010severe baseline symptoms (NRS \u2265\u20094) when available. PPAR agonists significantly reduced NRS scores at 3\u2009months (MD, \u22121.39; 95%\u2009CI: \u22122.49 to \u22120.29), 6\u2009months (MD, \u22121.17; 95%\u2009CI: \u22121.96 to \u22120.38) and 12\u2009months (MD, \u22121.73; 95%\u2009CI, \u22123.00 to \u22120.46); in individual agent analyses, bezafibrate and seladelpar reached statistical significance at two or more time points. While improvements were also noted in PBC\u201040 itch\u2010domain and 5D\u2010itch score, an impact on overall HRQoL as reflected by PBC\u201040 total score could not be demonstrated, with a lower level of certainty.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PPAR agonists, notably bezafibrate and seladelpar, reduce pruritus severity in PBC patients with moderate\u2010to\u2010severe symptoms and consistently improve itch\u2010specific outcomes. However, effects on global HRQoL remain uncertain. These findings underscore the incorporation of validated, symptom\u2010focused endpoints in future PBC trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.70634","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T11:21:05Z","timestamp":1774264865000},"page":"1190-1200","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Meta\u2010Analysis:\n                    <scp>PPAR<\/scp>\n                    Agonists for Pruritus and Quality of Life in Primary Biliary Cholangitis"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2653-2238","authenticated-orcid":false,"given":"Adrielly","family":"Martins","sequence":"first","affiliation":[{"name":"Schiff Center for Liver Diseases University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidah S.","family":"Khakoo","sequence":"additional","affiliation":[{"name":"Division of Digestive Diseases, Department of Medicine Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Corpechot","sequence":"additional","affiliation":[{"name":"Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, European Reference Network on Hepatological Diseases (ERN Rare\u2010Liver), saint\u2010Antoine Hospital, Assistance Publique \u2010 H\u00f4pitaux de Paris &amp; Inserm UMR_S938, Saint\u2010Antoine Research Center, Sorbonne University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Rousseau","sequence":"additional","affiliation":[{"name":"Clinical Research Platform of East of Paris, Saint\u2010Antoine Hospital, Assistance Publique \u2010 H\u00f4pitaux de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Louis Calder Memorial Library University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9263-948X","authenticated-orcid":false,"given":"Andreas E.","family":"Kremer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Z\u00fcrich University of Z\u00fcrich  Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Hassan","family":"Murad","sequence":"additional","affiliation":[{"name":"Evidence\u2010Based Practice Center, Kern Center for the Science of Healthcare Delivery Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahnaz","family":"Sultan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University of Minnesota and Minneapolis Veterans Affairs Medical Center  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Levy","sequence":"additional","affiliation":[{"name":"Schiff Center for Liver Diseases University of Miami Miller School of Medicine  Miami Florida USA"},{"name":"Division of Digestive Health and Liver Diseases, Department of Medicine University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01303-5"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30145"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.022"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-022-07581-x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/HC9.0000000000000635"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.06.034"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12026"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-0350"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41687-024-00722-y"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.70276"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2007.11.021"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.12.029"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22428"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/HC9.0000000000000612"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0000000000001109"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.10.001"},{"key":"e_1_2_11_18_1","unstructured":"FDA \u201cFDA Roundup: June 11 2024 \u2010 FDA Approval of Iqirvo (Elafibranor) Oral Tablets for the Treatment of Primary Biliary Cholangitis (PBC): The U.S. Food and Drug Administration \u201d(2024) https:\/\/www.fda.gov\/news\u2010events\/press\u2010announcements\/fda\u2010roundup\u2010june\u201011\u20102024."},{"key":"e_1_2_11_19_1","unstructured":"EMA.\u201cEuropean Medicines Agency Conditional Approval for Iqirvo (Elafibranor) \u201d(2024) https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/iqirvo."},{"key":"e_1_2_11_20_1","unstructured":"EMA \u201cSeladelpar (lyvdelzi) \u201d(2024) https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/seladelpar\u2010gilead."},{"key":"e_1_2_11_21_1","unstructured":"\u201cNDA 217899 (Seladelpar) Accelerated Approval \u201d(2024)."},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1714519"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2312100"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2306185"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000395"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.01.013"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.08.025"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.065862"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2009.09586.x"},{"key":"e_1_2_11_30_1","volume-title":"Methodological Expectations of Cochrane Intervention Reviews","author":"Higgins J. P. T.","year":"2023"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000001465"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2016.01.021"},{"key":"e_1_2_11_34_1","volume-title":"\u201cEndnote 20 ed,\u201d","author":"The Endnote Team","year":"2013"},{"key":"e_1_2_11_35_1","volume-title":"Covidence Systematic Review Software","author":"Veritas Health Innovation","year":"2024"},{"key":"e_1_2_11_36_1","volume-title":"The Retraction Watch Database","author":"Watch R.","year":"2018"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-14-135"},{"key":"e_1_2_11_38_1","unstructured":"A.Rohatgi \u201cWebPlotDigitizer \u201d5.2 ed."},{"key":"e_1_2_11_39_1","volume-title":"RStudio: Integrated Development Environment for R. 2024.12.0.467","author":"Posit Team","year":"2024"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39489.470347.AD"},{"key":"e_1_2_11_42_1","volume-title":"GRADEpro Guideline Development Tool","year":"2025"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2022.10.032"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(25)00192-X"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41687-018-0056-3"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.12.004"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2021.100370"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03906-1"},{"key":"e_1_2_11_49_1","volume-title":"Patient\u2010Focused Drug Development: Selecting, Developing, or Modifying Fit\u2010for\u2010Purpose Clinical Outcome Assessments. Guidance for Industry","author":"U.S. Food and Drug Administration","year":"2022"},{"key":"e_1_2_11_50_1","volume-title":"Rare Diseases: Considerations for the Development of Drugs and Biological Products. Guidance for Industry","author":"U.S. Food and Drug Administration","year":"2019"},{"key":"e_1_2_11_51_1","unstructured":"European Medicines Agency \u201cReflection Paper on Regulatory Requirements for the Development of Medicinal Products for Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC) European Medicines Agency \u201d(2023)."},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-6296(01)00130-8"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11136-019-02300-y"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11136-011-9903-x"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtauto.2021.100081"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2010.04512.x"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1177\/20406223221114198"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874192401004010120"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-002-1102-7"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2015.20"}],"container-title":["Alimentary Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.70634","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/apt.70634","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.70634","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T17:01:49Z","timestamp":1776445309000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apt.70634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,23]]},"references-count":59,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1111\/apt.70634"],"URL":"https:\/\/doi.org\/10.1111\/apt.70634","archive":["Portico"],"relation":{},"ISSN":["0269-2813","1365-2036"],"issn-type":[{"value":"0269-2813","type":"print"},{"value":"1365-2036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,23]]},"assertion":[{"value":"2025-12-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}