{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T05:29:50Z","timestamp":1791955790119,"version":"4.3.4"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:p>The interleukin (IL)\u201012 signaling cascade has been associated with primary biliary cholangitis (PBC). This multicenter, open\u2010label, proof\u2010of\u2010concept study evaluated the anti\u2010IL12\/23 monoclonal antibody, ustekinumab (90 mg subcutaneous at weeks 0 and 4, then every 8 weeks through week 20), in adults with PBC and an inadequate response to ursodeoxycholic acid therapy (i.e., alkaline phosphatase [ALP] &gt;1.67\u00d7 upper limit of normal [ULN] after \u22656 months). ALP response was defined as a &gt;40% decrease from baseline and ALP remission as ALP normalization (if baseline ALP 1.67\u00d7\u20102.8\u00d7 ULN) or &lt;1.67\u00d7 ULN (if baseline ALP &gt;2.8\u00d7 ULN). Changes in Enhanced Liver Fibrosis (ELF) scores and serum bile acids were also assessed. At baseline, patients had median disease duration of 3.2 years, median ELF score of 9.8, and highly elevated total bile acid concentration (median, 43.3\u00a0\u03bcmol\/L); 13 of 20 (65%) patients had baseline ALP &gt;3\u00d7 ULN. Although steady\u2010state serum ustekinumab concentrations were reached by week 12, no patient achieved ALP response or remission. Median percent ALP reduction from baseline to week 28 was 12.1%. ELF score decreased slightly from baseline to week 28 (median reduction: 0.173), and total serum bile acid concentrations decreased from baseline to week 28 (median reduction: 8.8\u00a0\u03bcmol\/L). No serious infections or discontinuations resulting from adverse events were reported through week 28. One patient had a serious upper gastrointestinal hemorrhage considered unrelated to test agent by the investigator. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Open\u2010label ustekinumab therapy, though associated with a modest decrease in ALP after 28 weeks of therapy, did not otherwise appreciably change ALP and overt proof\u2010of\u2010concept was not established as per prespecified primary endpoint of proposed efficacy. No new ustekinumab safety signals were observed. 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Eric","family":"Gershwin","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy & Immunology,The University of California School of Medicine,Davis,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Strauss","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC,Spring House,PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlyn J.","family":"Mayo","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern, Dallas,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Levy","sequence":"additional","affiliation":[{"name":"University of Miami,Miami,FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zou","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC,Spring 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