{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:14:26Z","timestamp":1789496066319,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We assessed and compared immunologic differences and associations with clinical response to guselkumab, a fully human interleukin (IL)\u201323p19 subunit inhibitor, in participants with active psoriatic arthritis (PsA) who were biologic\u2010naive or had inadequate response to tumor necrosis factor inhibitors (TNFi\u2010IR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum biomarker levels at baseline and after treatment with guselkumab 100 mg every 8\u2009weeks were compared between biologic\u2010naive (n\u00a0=\u00a0251) and TNFi\u2010IR (n\u00a0=\u00a093) subgroups identified in the pooled DISCOVER\u20101\/DISCOVER\u20102\/COSMOS data set. Baseline biomarker levels determined by achievement of week 24 clinical responses (\u226575%\/90% improvement in Psoriasis Area and Severity Index [PASI 75\/90], Investigator's Global Assessment [IGA] of psoriasis score 0\/1 and \u22652\u2010point improvement], \u226520% improvement in American College of Rheumatology criteria [ACR20]) were compared between prior treatment subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Baseline IL\u201022, TNF\u03b1, and beta defensin\u20102 (BD\u20102) levels were significantly lower in biologic\u2010naive than in TNFi\u2010IR participants. With guselkumab, week 24 IL\u201017A, IL\u201017F, IL\u201022, serum amyloid A, C\u2010reactive protein, IL\u20106, and BD\u20102 levels were significantly reduced from baseline in biologic\u2010naive and TNFi\u2010IR participants (\u22651.4\u2010fold difference, nominal\n                      <jats:italic>P<\/jats:italic>\n                      &lt;\u20090.05). Clinical responders to guselkumab exhibited significantly higher baseline levels of several biomarkers than nonresponders (IL\u201017A, IL\u201017F, BD\u20102 in biologic\u2010naive PASI 90 responders; IL\u201017A, BD\u20102 in TNFi\u2010IR IGA 0\/1 responders; IL\u201022, BD\u20102 in TNFi\u2010IR PASI 90 responders [nominal\n                      <jats:italic>P<\/jats:italic>\n                      &lt;\u20090.05]) and trended higher in TNFi\u2010IR ACR20 responders.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Guselkumab modulates IL\u201023 signaling and provides consistent pharmacodynamic effects in both biologic\u2010naive and TNFi\u2010IR PsA patients. Significantly elevated baseline IL\u201022, TNF\u03b1, and BD\u20102 levels and associations between baseline IL\u201022, IL\u201017A, and BD\u20102 levels and skin responses to guselkumab suggest greater dysregulation of IL\u201023\/Th17 signaling in patients with TNFi\u2010IR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42803","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T20:43:55Z","timestamp":1705956235000},"page":"894-904","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Modulation of Interleukin\u201023 Signaling With Guselkumab in\n                    <scp>Biologic\u2010Naive<\/scp>\n                    Patients Versus Tumor Necrosis Factor Inhibitor\u2013Inadequate Responders With Active Psoriatic Arthritis"],"prefix":"10.1002","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1802-7311","authenticated-orcid":false,"given":"Stefan","family":"Siebert","sequence":"first","affiliation":[{"name":"University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4756-663X","authenticated-orcid":false,"given":"Laura C.","family":"Coates","sequence":"additional","affiliation":[{"name":"University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8740-9615","authenticated-orcid":false,"given":"Georg","family":"Schett","sequence":"additional","affiliation":[{"name":"Friedrich\u2010Alexander Universit\u00e4t Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7594-6528","authenticated-orcid":false,"given":"Siba P.","family":"Raychaudhuri","sequence":"additional","affiliation":[{"name":"University of California Davis and Veterans Affairs Northern California Health Care System  Mather California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warner","family":"Chen","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC, Spring House  Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Gao","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC, Spring House  Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loqmane","family":"Seridi","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC, Spring House  Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7957-838X","authenticated-orcid":false,"given":"Soumya D.","family":"Chakravarty","sequence":"additional","affiliation":[{"name":"Janssen Scientific Affairs, LLC, Horsham, Pennsylvania, and Drexel University College of Medicine  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6005-3938","authenticated-orcid":false,"given":"May","family":"Shawi","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC  Titusville New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5213-257X","authenticated-orcid":false,"given":"Frederic","family":"Lavie","sequence":"additional","affiliation":[{"name":"Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson &amp; Johnson  Issy les Moulineaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9847-2996","authenticated-orcid":false,"given":"Mohamed","family":"Sharaf","sequence":"additional","affiliation":[{"name":"Janssen MEA  Dubai United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6063-3000","authenticated-orcid":false,"given":"Miriam","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Janssen Medical Affairs, LLC  Zug Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2059-7866","authenticated-orcid":false,"given":"Alexa P.","family":"Kollmeier","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; 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