{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:36:30Z","timestamp":1791466590574,"version":"4.3.4"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T00:00:00Z","timestamp":1548288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["2P60AR047784\u201006A2"],"award-info":[{"award-number":["2P60AR047784\u201006A2"]}],"id":[{"id":"10.13039\/100000069","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":[[2019,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the relationship between serum levels of S100A8\/A9 and S100A12 and the maintenance of clinically inactive disease during anti\u2013tumor necrosis factor (anti\u2010<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>) therapy and the occurrence of disease flare following withdrawal of anti\u2010<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> therapy in patients with polyarticular forms of juvenile idiopathic arthritis (JIA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this prospective, multicenter study, 137 patients with polyarticular\u2010course <jats:styled-content style=\"fixed-case\">JIA<\/jats:styled-content> whose disease was clinically inactive while receiving anti\u2010<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> therapy were enrolled. Patients were observed for an initial 6\u2010month phase during which anti\u2010<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> treatment was continued. For those patients who maintained clinically inactive disease over the 6 months, anti\u2010<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> was withdrawn and they were followed up for 8 months to assess for the occurrence of flare. Serum S100 levels were measured at baseline and at the time of anti\u2010<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> withdrawal. Spearman's rank correlation test, Mann\u2010Whitney U test, Kruskal\u2010Wallis test, receiver operating characteristic (<jats:styled-content style=\"fixed-case\">ROC<\/jats:styled-content>) curve, and Kaplan\u2010Meier survival analyses were used to assess the relationship between serum S100 levels and maintenance of clinically inactive disease and occurrence of disease flare after anti\u2010<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> withdrawal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Over the 6\u2010month initial phase with anti\u2010<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> therapy, the disease state reverted from clinically inactive to clinically active in 24 (18%) of the 130 evaluable patients with polyarticular\u2010course <jats:styled-content style=\"fixed-case\">JIA<\/jats:styled-content>; following anti\u2010<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> withdrawal, 39 (37%) of the 106 evaluable patients experienced a flare. Serum levels of S100A8\/A9 and S100A12 were elevated in up to 45% of patients. Results of the <jats:styled-content style=\"fixed-case\">ROC<\/jats:styled-content> analysis revealed that serum S100 levels did not predict maintenance of clinically inactive disease during anti\u2010<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> therapy nor did they predict disease flare after treatment withdrawal. Elevated levels of S100A8\/A9 were not predictive of the occurrence of a disease flare within 30 days, 60 days, 90 days, or 8 months following anti\u2010<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> withdrawal, and elevated S100A12 levels had a modest predictive ability for determining the risk of flare within 30, 60, and 90 days after treatment withdrawal. Serum S100A12 levels at the time of anti\u2010<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> withdrawal were inversely correlated with the time to disease flare (r = \u22120.36).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Serum S100 levels did not predict maintenance of clinically inactive disease or occurrence of disease flare in patients with polyarticular\u2010course <jats:styled-content style=\"fixed-case\">JIA<\/jats:styled-content>, and S100A12 levels were only moderately, and inversely, correlated with the time to disease flare.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40727","type":"journal-article","created":{"date-parts":[[2018,9,18]],"date-time":"2018-09-18T03:33:07Z","timestamp":1537241587000},"page":"451-459","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Serum S100A8\/A9 and S100A12 Levels in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis: Relationship to Maintenance of Clinically Inactive Disease During Anti\u2013Tumor Necrosis Factor Therapy and Occurrence of Disease Flare After Discontinuation of Therapy"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9247-4729","authenticated-orcid":false,"given":"Claas H.","family":"Hinze","sequence":"first","affiliation":[{"name":"University Hospital M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Foell","sequence":"additional","affiliation":[{"name":"University Hospital M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne L.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center  Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Spalding","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Foundations  Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth S.","family":"Gottlieb","sequence":"additional","affiliation":[{"name":"The Steven and Alexandra Cohen Children\u2019s Medical Center of New York  New Hyde Park New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula W.","family":"Morris","sequence":"additional","affiliation":[{"name":"University of Arkansas for Medical Science  Little Rock"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Kimura","sequence":"additional","affiliation":[{"name":"Hackensack University Medical Center Joseph M. 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