{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T17:48:36Z","timestamp":1773683316280,"version":"3.50.1"},"reference-count":28,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"unspecified","delay-in-days":74,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"ERA PerMed ScandRA","award":["2021-00757"],"award-info":[{"award-number":["2021-00757"]}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2023-01827"],"award-info":[{"award-number":["2023-01827"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"name":"SQUEEZE","award":["101095052"],"award-info":[{"award-number":["101095052"]}]},{"DOI":"10.13039\/501100007949","name":"Reumatikerf\u00f6rbundet","doi-asserted-by":"publisher","award":["R-1013521"],"award-info":[{"award-number":["R-1013521"]}],"id":[{"id":"10.13039\/501100007949","id-type":"DOI","asserted-by":"publisher"}]},{"name":"SPIDERR","award":["101080711"],"award-info":[{"award-number":["101080711"]}]},{"name":"ALF","award":["FoUI-1000733"],"award-info":[{"award-number":["FoUI-1000733"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2026,2,16]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Rheumatoid arthritis (RA) is a disease with a heterogeneous phenotype. Partly, this heterogeneity may be concealed by metrics such as 28-joint disease activity score (DAS28) that may assign similar scores to dissimilar phenotypes. To explore how individual patient profiles may be separated, we developed three classification schemes and compared these with DAS28 in newly diagnosed RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We selected patients aged 18\u2013100 years, newly diagnosed with RA between 2012 and 2022 and registered in the Swedish Rheumatology Quality Register. We devised three alternative classifications based on (i) a subjective-objective decomposition of the DAS28 (seven levels), (ii) clinical experience-based cut-offs for each of the DAS28 components (five levels) and (iii) a data-driven Gaussian Mixture Model (five clusters). For each classification, we calculated descriptive statistics for clinical characteristics, demographic variables and comorbidity histories, and contrasted these with those based on DAS28 categories in our study population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 6624 patients with complete data on all included variables. In each of the alternative classifications, subjectively dominated and objectively dominated subsets captured differences regarding comorbidity histories not detectable in the DAS28 categories. Across all alternative classifications, subjectively dominated subsets had lower work ability than objectively dominated subsets and included 50%\u2013300%\u2009more patients with pain and psychiatric diagnoses prior to RA diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Separating subjective and objective dimensions reveals different RA patient profiles that are grouped together by DAS28, demonstrating the extent to which DAS28 is confounded by factors beyond RA disease activity. Disentangling and treating heterogeneous RA patient profiles may therefore require more granular disease activity classification systems.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2025-005955","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T16:55:27Z","timestamp":1773680127000},"page":"e005955","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Can alternative means of phenotyping rheumatoid arthritis reduce its apparent heterogeneity? A comparison of three disease activity classifications with DAS28"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9745-354X","authenticated-orcid":false,"given":"Simon","family":"Steiger","sequence":"first","affiliation":[{"name":"Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3380-5342","authenticated-orcid":false,"given":"Helga","family":"Westerlind","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, 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":"Clinical Epidemiology Division, 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":"Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden"},{"name":"Rheumatology, Theme Inflammation and Ageing, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"2026031609552070000_12.1.e005955.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2004.09.002"},{"key":"2026031609552070000_12.1.e005955.2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380107"},{"key":"2026031609552070000_12.1.e005955.3","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keg072"},{"key":"2026031609552070000_12.1.e005955.4","doi-asserted-by":"publisher","DOI":"10.1186\/ar1740"},{"key":"2026031609552070000_12.1.e005955.5","doi-asserted-by":"crossref","first-page":"103423","DOI":"10.1016\/j.autrev.2023.103423","article-title":"Residual pain in rheumatoid arthritis: Is it a real problem?","volume":"22","author":"Sarzi-Puttini","year":"2023","journal-title":"Autoimmun Rev"},{"key":"2026031609552070000_12.1.e005955.6","first-page":"S","article-title":"The Swedish Rheumatology Quality Register: optimisation of rheumatic disease assessments using register-enriched data","volume":"32","author":"Eriksson","year":"2014","journal-title":"Clin Exp Rheumatol"},{"key":"2026031609552070000_12.1.e005955.7","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-019-00511-8"},{"key":"2026031609552070000_12.1.e005955.8","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2458-11-450","article-title":"External review and validation of the Swedish national inpatient register","volume":"11","author":"Ludvigsson","year":"2011","journal-title":"BMC Public Health"},{"key":"2026031609552070000_12.1.e005955.9","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1294"},{"key":"2026031609552070000_12.1.e005955.10","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2022-002700","article-title":"Comorbidities and treatment patterns in early rheumatoid arthritis: a nationwide Swedish study","volume":"8","author":"Tidblad","year":"2022","journal-title":"RMD Open"},{"key":"2026031609552070000_12.1.e005955.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2009.10.001"},{"key":"2026031609552070000_12.1.e005955.12","unstructured":"van Leeuwen D . GaussianMixtures.jl: large scale Gaussian mixture models [online]. Available: https:\/\/github.com\/davidavdav\/GaussianMixtures.jl [Accessed 12 Aug 2024]."},{"key":"2026031609552070000_12.1.e005955.13","doi-asserted-by":"publisher","DOI":"10.1137\/141000671"},{"key":"2026031609552070000_12.1.e005955.14","doi-asserted-by":"publisher","DOI":"10.21105\/joss.03349"},{"key":"2026031609552070000_12.1.e005955.15","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-223413"},{"key":"2026031609552070000_12.1.e005955.16","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2023-003111","article-title":"Register-based observational study of associations between inflammatory remission, formal treatment targets and the use of disease-modifying antirheumatic drugs among patients with early rheumatoid arthritis","volume":"9","author":"Lindqvist","year":"2023","journal-title":"RMD Open"},{"key":"2026031609552070000_12.1.e005955.17","doi-asserted-by":"publisher","DOI":"10.1002\/art.24430"},{"key":"2026031609552070000_12.1.e005955.18","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.134445"},{"key":"2026031609552070000_12.1.e005955.19","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2021-002034","article-title":"Reexamining remission definitions in rheumatoid arthritis: considering the Twenty-eight-joint Disease Activity Score, C-reactive protein level and patient global assessment","volume":"7","author":"Felson","year":"2021","journal-title":"RMD Open"},{"key":"2026031609552070000_12.1.e005955.20","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez049"},{"key":"2026031609552070000_12.1.e005955.21","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-201506"},{"key":"2026031609552070000_12.1.e005955.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2010.01.011"},{"key":"2026031609552070000_12.1.e005955.23","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1002\/art.41379","article-title":"Latent Class Trajectory Modeling of 2-component Disease Activity Score in 28 Joints Identifies Multiple Rheumatoid Arthritis Phenotypes of Response to Biologic Disease-Modifying Antirheumatic Drugs","volume":"72","author":"Dagliati","year":"2020","journal-title":"Arthritis Rheumatol"},{"key":"2026031609552070000_12.1.e005955.24","doi-asserted-by":"crossref","first-page":"101735","DOI":"10.1016\/j.berh.2021.101735","article-title":"Treating-to-target in rheumatology: Theory and practice","volume":"36","author":"Duarte","year":"2022","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"2026031609552070000_12.1.e005955.25","doi-asserted-by":"crossref","first-page":"101439","DOI":"10.1016\/j.berh.2019.101439","article-title":"Pain without inflammation in rheumatic diseases","volume":"33","author":"Lampa","year":"2019","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"2026031609552070000_12.1.e005955.26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05566.x"},{"key":"2026031609552070000_12.1.e005955.27","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2022-002478","article-title":"The effect of tofacitinib on residual pain in patients with rheumatoid arthritis and psoriatic arthritis","volume":"8","author":"Dougados","year":"2022","journal-title":"RMD Open"},{"key":"2026031609552070000_12.1.e005955.28","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2019-001131","article-title":"Comparative effectiveness of improvement in pain and physical function for baricitinib versus adalimumab, tocilizumab and tofacitinib monotherapies in rheumatoid arthritis patients who are na\u00efve to treatment with biologic or conventional synthetic disease-modifying antirheumatic drugs: a matching-adjusted indirect comparison","volume":"6","author":"Fautrel","year":"2020","journal-title":"RMD Open"}],"container-title":["RMD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rmdopen-2025-005955","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T16:55:31Z","timestamp":1773680131000},"score":1,"resource":{"primary":{"URL":"https:\/\/rmdopen.bmj.com\/lookup\/doi\/10.1136\/rmdopen-2025-005955"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,3,16]]},"published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1136\/rmdopen-2025-005955"],"URL":"https:\/\/doi.org\/10.1136\/rmdopen-2025-005955","relation":{},"ISSN":["2056-5933"],"issn-type":[{"value":"2056-5933","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]}}}