{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:15:26Z","timestamp":1787019326018,"version":"build-2736575974"},"reference-count":50,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research & Development, LLC","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Musculoskeletal"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Guselkumab (human monoclonal antibody) selectively inhibits the interleukin (IL)-23p19 subunit.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>Assess the longer-term pharmacodynamic effects of guselkumab and explore associations between such effects and clinical responses in patients with active psoriatic arthritis (PsA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>\n                      DISCOVER-2 randomized 739 biologic-na\u00efve patients with active PsA (swollen\/tender joint counts each \u2a7e5, C-reactive protein (CRP) \u2a7e0.6\u2009mg\/dL) to guselkumab (100\u2009mg every 4\u2009weeks (Q4W) or at Weeks 0, 4, and then Q8W) or placebo. Guselkumab-randomized participants with available serum biomarker data (randomly selected to reflect demographic and disease characteristics of the DISCOVER-2 population) comprised inflammatory (\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      \u2009=\u2009100) and collagen (\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      \u2009=\u2009178) biomarker cohorts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Pharmacodynamic effects of guselkumab through 2 years on inflammatory and collagen biomarker levels (general linear model) and associations between biomarkers and improvements in composite measures of joint, skin, and overall disease activity (Spearman linear regression) through 2 years were assessed. The relationship between the pharmacodynamic effects of guselkumab and achieving \u2a7e50% improvement in the American College of Rheumatology response criteria (ACR50) was assessed using a general linear model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      With guselkumab, pharmacodynamic effects on inflammatory (CRP, IL-6, serum amyloid A (SAA), IL-17A, IL-17F, IL-22, and beta-defensin 2 (BD-2)) and collagen (matrix metalloproteinase-degradation type I, III, IV, and VI collagen (C1M, C3M, C4M, and C6M)) biomarker levels were sustained or enhanced through Week 100. Throughout follow-up timepoints (Week 24\/52\/100), decreases in CRP, IL-6, C1M, and C6M levels correlated (\n                      <jats:italic toggle=\"yes\">r<\/jats:italic>\n                      \u2009=\u20090.26\u20130.30;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.05) with improved joint disease activity (Disease Activity in Psoriatic Arthritis); decreases in IL-17A, IL-17F, IL-22, and BD-2 levels correlated (\n                      <jats:italic toggle=\"yes\">r<\/jats:italic>\n                      \u2009=\u20090.34\u20130.58;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.05) with improved skin disease (Psoriasis Area and Severity Index); and decreases in C1M, C3M, C4M, and C6M correlated (\n                      <jats:italic toggle=\"yes\">r<\/jats:italic>\n                      \u2009=\u20090.27\u20130.31;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.05) with improved overall disease activity (Psoriatic Arthritis Disease Activity Score). Significantly (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.05) greater reductions from baseline at Week 100 in CRP, IL-6, SAA, and C1M levels were observed in participants improving from Week 24 ACR50 nonresponse to Week 100 ACR50 response and were accompanied by a significant decrease in C1M from Week 24 to Week 100 versus nonresponders at both Weeks 24 and 100.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>In biologic-na\u00efve participants with active PsA, guselkumab elicited substantial and enduring reductions in biomarkers that were associated with durable improvements in joint, skin, and overall disease activity through 2 years of DISCOVER-2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration:<\/jats:title>\n                    <jats:p>NCT03158285 (clinicaltrials.gov identifier).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1759720x241283536","type":"journal-article","created":{"date-parts":[[2024,10,27]],"date-time":"2024-10-27T10:57:27Z","timestamp":1730026647000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Correlation of changes in inflammatory and collagen biomarkers with durable guselkumab efficacy through 2 years in participants with active psoriatic arthritis: results from a phase III randomized controlled trial"],"prefix":"10.1177","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1802-7311","authenticated-orcid":false,"given":"Stefan","family":"Siebert","sequence":"first","affiliation":[{"name":"School of Infection &amp; Immunity, University of Glasgow, Sir Graeme Davies Building, 4th Floor, 120 University Place, Glasgow G12 8TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Schett","sequence":"additional","affiliation":[{"name":"Department of Medicine 3\u2014Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siba P.","family":"Raychaudhuri","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis, School of Medicine, Sacramento, CA, USA"},{"name":"VA Northern California Health Care System, Mather, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Guma","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Autoimmunity and Inflammation, Department of Medicine, University of California San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warner","family":"Chen","sequence":"additional","affiliation":[{"name":"Immunology, Janssen Research &amp; Development, LLC, Spring House, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Gao","sequence":"additional","affiliation":[{"name":"Immunology, Janssen Research &amp; Development, LLC, Spring House, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumya D.","family":"Chakravarty","sequence":"additional","affiliation":[{"name":"Immunology, Janssen Scientific Affairs, LLC, a Johnson &amp; Johnson Company, Horsham, PA, USA"},{"name":"Division of Rheumatology, Drexel University College of Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Lavie","sequence":"additional","affiliation":[{"name":"Immunology Global Medical Affairs, Janssen Cilag Global Medical Affairs, Issy les Moulineaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Proton","family":"Rahman","sequence":"additional","affiliation":[{"name":"Craig L. 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