{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:58:39Z","timestamp":1790387919422,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis Care &amp; Research"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Despite advances in treat\u2010to\u2010target strategies, a subset of patients with rheumatoid arthritis (RA) remains refractory to multiple therapies and is classified as having difficult\u2010to\u2010treat RA (D2T\u2010RA). Although EULAR has proposed classification criteria for D2T\u2010RA, these patients remain variably identified in real\u2010world practice because of heterogeneous applications. We aimed to compare the preformance of published applications of the EULAR D2T\u2010RA criteria in a real\u2010world RA cohort\u00a0and to determine weather the timing of D2T\u2010RA development could distinguish early from late D2T\u2010RA phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using data from the Ontario Best Practices Research Initiative, a longitudinal real\u2010world RA registry, we evaluated four literature\u2010derived adaptations of the EULAR D2T\u2010RA definition among patients initiating their first advanced therapy. These definitions differed in disease activity requirements, follow\u2010up duration, and treatment count thresholds. We assessed prevalence, agreement between definitions, and explored different temporal anchors for classifying early versus late D2T\u2010RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 1,121 patients with RA (mean age 56.0 years; 80.7% female; mean disease duration of 8.4 years), 202 (18%) fulfilled at least one of four D2T\u2010RA definitions. Prevalence varied substantially across definitions, ranging from 5.5% (definition 4) to 11.7% (definition 2). Definitions 1 and 2, which incorporated multiple disease activity measures, identified the largest proportion of patients, whereas definition 4, which is defined solely by initiation of a third advanced therapy, was most restrictive. Overlap between definitions was modest, with only 44% of patients meeting all definitions 1 through 3, whereas definition 4 identified a distinct group with no overlap with the other definitions, suggesting that these classification approaches capture different patient subsets and are not interchangeable. In temporal analyses, anchoring the D2T\u2010RA onset to the initiation of the first advanced therapy, a two\u2010year threshold\u2014selected for its clinical relevance and balanced group sizes\u2014classified approximately 40% of patients as early and approximately 60% as late D2T\u2010RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The applications of D2T\u2010RA criteria are not interchangeable and vary widely in patient capture. A two\u2010year threshold anchored to the first initiation of advanced therapy offered a clinically balanced early\u2013late D2T\u2010RA framework. Harmonized, multidimensional definitions incorporating disease activity and temporal stratification are needed to improve phenotyping, prognostication, and cross\u2010study comparability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acr.80161","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:39:10Z","timestamp":1789468750000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Defining Difficult\u2010to\u2010Treat Rheumatoid Arthritis in Routine Care: Comparative Performance of Published Criteria and Description of Early and Late Difficult\u2010to\u2010Treat Rheumatoid Arthritis Phenotypes"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1165-1173","authenticated-orcid":false,"given":"Rahaf Zyad","family":"Attar","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine King Abdulaziz University  Jeddah Saudi 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Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1721-190X","authenticated-orcid":false,"given":"Carter","family":"Thorne","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Southlake Regional Health Centre  Newmarket Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1479-5302","authenticated-orcid":false,"given":"Janet","family":"Pope","sequence":"additional","affiliation":[{"name":"University of Western Ontario  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0354-4794","authenticated-orcid":false,"given":"Timothy","family":"Kwok","sequence":"additional","affiliation":[{"name":"Division of Rheumatology University of Toronto  Toronto Ontario Canada"},{"name":"Holland Bone and Joint Program Sunnybrook Research Institute  Toronto Ontario 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