{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T15:43:44Z","timestamp":1773675824695,"version":"3.50.1"},"reference-count":9,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,11,24]],"date-time":"2015-11-24T00:00:00Z","timestamp":1448323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"F. Hoffmann-La Roche, Ltd"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis Care &amp;amp; Research"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess the flare rate using published criteria (Disease Activity Score in 28 joints [DAS28\u20102] increase between visits of &gt;1.2 or &gt;0.6 if current DAS28 \u22653.2) in patients receiving constant treatment, and to compare published flare criteria to criteria used by study investigators after biologic treatment discontinuation in the ACT\u2010RAY study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with rheumatoid arthritis (n\u2009=\u2009553) were randomized to add tocilizumab to ongoing methotrexate, or switch to tocilizumab plus placebo. If DAS28 \u22643.2 occurred at week 24, treatment remained constant until week 52; here we assessed the DAS28\u20102 flare rate. Between weeks 52 and 104, patients in sustained remission (DAS28 &lt;2.6 at 2 consecutive visits 12 weeks apart) discontinued tocilizumab and were assessed every 4 weeks. Per protocol, flare was defined as a worsening of disease activity that required treatment beyond the permitted therapy based on investigator opinions (investigator flare) and was compared with the DAS28\u20102 definition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After tocilizumab discontinuation, DAS28\u20102 was sensitive (88\u2013100%), but not specific (57\u201365%), for detecting investigator flare. Under constant treatment, DAS28\u20102 criteria were met in 136 cases per 100 patient\u2010years despite stable disease activity. Sustained flares were infrequent. Other DAS28\u2010based criteria led to similar conclusions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>DAS28\u2010based flare occurred more often than investigator\u2010defined flares after biologic agent discontinuation. More stringent criteria may be more appropriate for clinical practice.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr.22633","type":"journal-article","created":{"date-parts":[[2015,6,2]],"date-time":"2015-06-02T10:54:59Z","timestamp":1433242499000},"page":"1762-1766","source":"Crossref","is-referenced-by-count":12,"title":["Evaluation of the Disease Activity Score in Twenty\u2010Eight Joints\u2013Based Flare Definitions in Rheumatoid Arthritis: Data From a Three\u2010Year Clinical Trial"],"prefix":"10.1002","volume":"67","author":[{"given":"Maxime","family":"Dougados","sequence":"first","affiliation":[{"name":"H\u00f4pital Cochin Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom W. J.","family":"Huizinga","sequence":"additional","affiliation":[{"name":"Leiden University Medical Centre Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernest H.","family":"Choy","sequence":"additional","affiliation":[{"name":"Cardiff University School of Medicine Cardiff UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"Clifton O.","family":"Bingham","sequence":"additional","affiliation":[{"name":"Johns Hopkins University Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maher","family":"Aassi","sequence":"additional","affiliation":[{"name":"F. Hoffmann\u2010La Roche Ltd. Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corrado","family":"Bernasconi","sequence":"additional","affiliation":[{"name":"F. Hoffmann\u2010La Roche Ltd. Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,11,24]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.131252"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202281"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204761"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205752"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12553"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203496"},{"issue":"10","key":"e_1_2_5_8_1","first-page":"S776","article-title":"A multicenter, randomized, controlled, open\u2010label pilot study of the feasibility of discontinuation of adalimumab in rheumatoid arthritis patients in stable clinical remission [abstract]","author":"Chatzidionysiou K","year":"2012","journal-title":"Arthritis Rheum"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-013-2390-4"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203243"}],"container-title":["Arthritis Care &amp; Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Facr.22633","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Facr.22633","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acr.22633","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acr.22633","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acr.22633","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T15:07:23Z","timestamp":1759417643000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/acr.22633"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,24]]},"references-count":9,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["10.1002\/acr.22633"],"URL":"https:\/\/doi.org\/10.1002\/acr.22633","archive":["Portico"],"relation":{},"ISSN":["2151-464X","2151-4658"],"issn-type":[{"value":"2151-464X","type":"print"},{"value":"2151-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,24]]}}}