{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T13:11:20Z","timestamp":1767791480954,"version":"3.49.0"},"reference-count":20,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"unspecified","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007687","name":"Svenska L\u00e4kares\u00e4llskapet","doi-asserted-by":"publisher","award":["SLS-974197"],"award-info":[{"award-number":["SLS-974197"]}],"id":[{"id":"10.13039\/501100007687","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009806","name":"Ulla och Gustaf af Ugglas Stiftelse","doi-asserted-by":"publisher","award":["2023-02488"],"award-info":[{"award-number":["2023-02488"]}],"id":[{"id":"10.13039\/501100009806","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"publisher","award":["KI Research Foundation Grants -2020-02416"],"award-info":[{"award-number":["KI Research Foundation Grants -2020-02416"]}],"id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"crossref","award":["2023-01827"],"award-info":[{"award-number":["2023-01827"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"name":"ALF","award":["FoUI-1000733"],"award-info":[{"award-number":["FoUI-1000733"]}]},{"DOI":"10.13039\/501100004785","name":"NORDFORSK","doi-asserted-by":"crossref","award":["90825"],"award-info":[{"award-number":["90825"]}],"id":[{"id":"10.13039\/501100004785","id-type":"DOI","asserted-by":"crossref"}]},{"name":"ERA PerMed ScandRA","award":["2021-00757"],"award-info":[{"award-number":["2021-00757"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,9,24]]},"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Multiple discontinuations of biologic (b-) or targeted synthetic (ts-) disease-modifying antirheumatic drugs (DMARDs) may indicate difficult-to-treat disease. We aimed to assess the occurrence of b\/tsDMARD discontinuations in patients with rheumatoid arthritis (RA), specifically how this varies by definition, across patient subsets and over time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Observational cohort study using data from the Swedish Rheumatology Quality Register on patients diagnosed with RA between 2010 and 2019. We identified three populations: (1) newly diagnosed (N=17\u2009780), (2) initiating a first-ever DMARD (N=18\u2009038) and (3) initiating a first-ever b\/tsDMARD (N=8075). In each, we assessed the proportions and characteristics of patients fulfilling either of seven alternative DMARD discontinuation criteria (each encompassing a unique combination of number and type(s) of b\/tsDMARD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At 4.5 years of follow-up, 10% in populations (1) and (2), and 25% in (3), had discontinued \u22652 b\/tsDMARDs with different modes of action. The proportions meeting each of the other six definitions ranged from 0.3% to 10% in (1) and (2), and 1% to 25% in (3). Regardless of definition or time, the characteristics of discontinuers across populations (1) through (3) remained largely similar.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Applying treatment discontinuation-based definitions to an unselected RA population identifies widely varying proportions of patients with largely similar characteristics. Quantitatively, treatment-based definitions, follow-up time and study population must be clearly specified; qualitatively, the specific definition may be less critical.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2025-005617","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T10:10:18Z","timestamp":1760523018000},"page":"e005617","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Multiple DMARD discontinuations in rheumatoid arthritis: how often and in what patients? Results from a national clinical RA register"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1889-8006","authenticated-orcid":false,"given":"Emma","family":"Wettersand","sequence":"first","affiliation":[{"name":"Karolinska Institute Department of Medicine Solna, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3817-8288","authenticated-orcid":false,"given":"Daniela","family":"di Giuseppe","sequence":"additional","affiliation":[{"name":"Karolinska Institute Department of Medicine Solna, Stockholm, Sweden"},{"name":"Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0433-0616","authenticated-orcid":false,"given":"Johan","family":"Askling","sequence":"additional","affiliation":[{"name":"Karolinska Institute Department of Medicine Solna, Stockholm, Sweden"},{"name":"Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2669-1247","authenticated-orcid":false,"given":"Katerina","family":"Chatzidionysiou","sequence":"additional","affiliation":[{"name":"Karolinska Institute Department of Medicine Solna, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"2026010700551304000_11.4.e005617.1","doi-asserted-by":"crossref","DOI":"10.1186\/s13075-015-0716-0","article-title":"Ten years of change in clinical disease status and treatment in rheumatoid arthritis: results based on standardized monitoring of patients in an ordinary outpatient clinic in southern Norway","volume":"17","author":"Haugeberg","year":"2015","journal-title":"Arthritis Res Ther"},{"key":"2026010700551304000_11.4.e005617.2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.049338"},{"key":"2026010700551304000_11.4.e005617.3","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-209562"},{"key":"2026010700551304000_11.4.e005617.4","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1093\/rheumatology\/kex352","article-title":"Improved flare and remission pattern in rheumatoid arthritis over recent decades: a population-based study","volume":"56","author":"Raheel","year":"2017","journal-title":"Rheumatology (Oxford)"},{"key":"2026010700551304000_11.4.e005617.5","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-217344"},{"key":"2026010700551304000_11.4.e005617.6","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-212862"},{"key":"2026010700551304000_11.4.e005617.7","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-213378"},{"key":"2026010700551304000_11.4.e005617.8","doi-asserted-by":"crossref","first-page":"5247","DOI":"10.1093\/rheumatology\/keab209","article-title":"Characteristics of patients with difficult-to-treat rheumatoid arthritis in clinical practice","volume":"60","author":"Takanashi","year":"2021","journal-title":"Rheumatology (Oxford)"},{"key":"2026010700551304000_11.4.e005617.9","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1002\/art.42767","article-title":"Poly-Refractory Rheumatoid Arthritis: An Uncommon Subset of Difficult to Treat Disease With Distinct Inflammatory and Noninflammatory Phenotypes","volume":"76","author":"David","year":"2024","journal-title":"Arthritis Rheumatol"},{"key":"2026010700551304000_11.4.e005617.10","doi-asserted-by":"crossref","first-page":"152421","DOI":"10.1016\/j.semarthrit.2024.152421","article-title":"Reasons for multiple biologic and targeted synthetic DMARD switching and characteristics of treatment refractory rheumatoid arthritis","volume":"66","author":"McDermott","year":"2024","journal-title":"Semin Arthritis Rheum"},{"key":"2026010700551304000_11.4.e005617.11","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1093\/rheumatology\/keae265","article-title":"Predictive factors and treatment outcomes associated with difficult-to-treat rheumatoid arthritis conditions: the ANSWER cohort study","volume":"63","author":"Watanabe","year":"2024","journal-title":"Rheumatology (Oxford)"},{"key":"2026010700551304000_11.4.e005617.12","doi-asserted-by":"crossref","first-page":"3866","DOI":"10.1093\/rheumatology\/kead143","article-title":"Characteristics of patients with difficult-to-treat rheumatoid arthritis in a French single-centre hospital","volume":"62","author":"Hecquet","year":"2023","journal-title":"Rheumatology (Oxford)"},{"key":"2026010700551304000_11.4.e005617.13","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2474-15-432","article-title":"Validation of the rheumatoid arthritis diagnosis in the Swedish National Patient Register: a cohort study from Stockholm County","volume":"15","author":"Waldenlind","year":"2014","journal-title":"BMC Musculoskelet Disord"},{"key":"2026010700551304000_11.4.e005617.14","doi-asserted-by":"publisher","DOI":"10.3109\/03009742.2014.927918"},{"key":"2026010700551304000_11.4.e005617.15","first-page":"1398","article-title":"Challenges and insights in managing difficult-to-treat rheumatoid arthritis: real-world clinical perspectives","volume":"42","author":"Alp","year":"2024","journal-title":"Clin Exp Rheumatol"},{"key":"2026010700551304000_11.4.e005617.16","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2023-003808","article-title":"Patterns of comorbidities differentially affect long-term functional evolution and disease activity in patients with \u201cdifficult to treat\u201d rheumatoid arthritis","volume":"10","author":"Bertsias","year":"2024","journal-title":"RMD Open"},{"key":"2026010700551304000_11.4.e005617.17","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2022-002842","article-title":"Difficult-to-treat rheumatoid arthritis (D2T RA): clinical issues at early stages of disease","volume":"9","author":"Leon","year":"2023","journal-title":"RMD Open"},{"key":"2026010700551304000_11.4.e005617.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2019.02.004"},{"key":"2026010700551304000_11.4.e005617.19","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1002\/acr.21710","article-title":"Association of obesity with worse disease severity in rheumatoid arthritis as well as with comorbidities: A long\u2010term followup from disease onset","volume":"65","author":"Ajeganova","year":"2013","journal-title":"Arthritis Care & Research"},{"key":"2026010700551304000_11.4.e005617.20","first-page":"1135","article-title":"Difficult-to-treat rheumatoid arthritis: an area of unmet clinical need","volume":"57","author":"de Hair","year":"2018","journal-title":"Rheumatology (Oxford)"}],"container-title":["RMD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rmdopen-2025-005617","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T08:55:23Z","timestamp":1767776123000},"score":1,"resource":{"primary":{"URL":"https:\/\/rmdopen.bmj.com\/lookup\/doi\/10.1136\/rmdopen-2025-005617"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":20,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,10,15]]},"published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1136\/rmdopen-2025-005617"],"URL":"https:\/\/doi.org\/10.1136\/rmdopen-2025-005617","relation":{},"ISSN":["2056-5933"],"issn-type":[{"value":"2056-5933","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]}}}