{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:38:08Z","timestamp":1793147888462,"version":"4.5.0"},"reference-count":21,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"unspecified","delay-in-days":57,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Eli Lilly"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2026,5,3]]},"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate whether in undifferentiated arthritis (UA) it is beneficial to start early treatment with disease-modifying antirheumatic drugs (DMARDs) compared with symptomatic therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The Induction of Cure in Early Arthritis study is a 3-month multicentre single-blinded randomised controlled trial followed by a 9-month observational period. Patients with early DMARD-na\u00efve UA (arthritis \u22652 joints, not fulfilling American College of Rheumatology (ACR)\/European Alliance of Associations for Rheumatology (EULAR) 2010 Rheumatoid Arthritis criteria) received a glucocorticoid injection (40 mg intra-articular or intramuscular) and were randomised (1:1:1) to a 3-month intervention with (1) non-steroidal anti-inflammatory drugs (NSAIDs) in standard daily dose or (2) methotrexate (MTX) 15 mg\/week increased to 25 mg\/week or (3) baricitinib 4 mg\/day. Primary endpoint was Disease Activity Score (DAS) (44\/53 joints) improvement at 3 months. Differences between treatment arms were assessed with analysis of covariance, adjusted for baseline DAS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients were randomised to NSAID (n=29), MTX (n=28) or baricitinib (n=28). After 3 months, baricitinib gave a significant improvement in DAS compared with NSAIDs: adjusted mean change in DAS: \u22120.52 (95% CI \u22120.93 to \u22120.11; p=0.01). MTX gave a numerically similar improvement: \u22120.39 (95% CI \u22120.84 to 0.06, p=0.09). Although non-significant, at 12 months DAS was lowest in the MTX treatment arm 1.3 (SD 0.7), NSAID 1.6 (SD 0.9), baricitinib 1.7 (SD 0.9), p=0.38. Incidence rates of severe adverse events remained low during the study across all treatment arms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients with UA, early DMARD treatment led to greater improvement in disease activity over 3 months compared with NSAIDs, with the improvement for baricitinib reaching statistical significance. Over 12 months, disease activity was not significantly different across treatment arms, with overall favourable outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2026-006828","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T15:15:20Z","timestamp":1779981320000},"page":"e006828","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Induction of Cure in Early Arthritis (I CEA): results of a randomised clinical trial to compare three treatment strategies in recent onset undifferentiated arthritis"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6936-5217","authenticated-orcid":false,"given":"Isabell S","family":"Nevins","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0721-9913","authenticated-orcid":false,"given":"Joy Ardjuna","family":"van der Pol","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotte","family":"Van Ouwerkerk","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory S","family":"Helmich","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Bos","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Frisius Medical Center, Leeuwarden, The Netherlands"},{"name":"Department of Rheumatology, Nij Smellinghe Hospital, Drachten, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sjoerd M","family":"Van Der Kooij","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Haga Hospital, The Hague, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald E","family":"Vonkeman","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Medisch Spectrum Twente, Enschede, The Netherlands"},{"name":"Department of Psychology, Health and Technology, University of Twente, Enschede, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Bijsterbosch","sequence":"additional","affiliation":[{"name":"Rheumatology, Amphia Hospital, Breda, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6628-6222","authenticated-orcid":false,"given":"Pascal Hendrik Pieter","family":"de Jong","sequence":"additional","affiliation":[{"name":"Rheumatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6071-0261","authenticated-orcid":false,"given":"Melek","family":"G\u00fcler-Y\u00fcksel","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Maasstad Hospital, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"B\u00f6hringer","sequence":"additional","affiliation":[{"name":"Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"Department of Pharmacology and Toxicology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7033-7520","authenticated-orcid":false,"given":"Tom W J","family":"Huizinga","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8448-7407","authenticated-orcid":false,"given":"Floris A","family":"van Gaalen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7136-5248","authenticated-orcid":false,"given":"Sytske Anne","family":"Bergstra","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"2026052808150955000_12.2.e006828.1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.5152\/eurjrheum.2017.16006","article-title":"Pre-rheumatoid arthritis and its prevention","volume":"4","author":"Paul","year":"2017","journal-title":"Eur J Rheumatol"},{"key":"2026052808150955000_12.2.e006828.2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210602"},{"key":"2026052808150955000_12.2.e006828.3","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-223356"},{"key":"2026052808150955000_12.2.e006828.4","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2018-000870","article-title":"Window of opportunity in rheumatoid arthritis - definitions and supporting evidence: from old to new perspectives","volume":"5","author":"Burgers","year":"2019","journal-title":"RMD Open"},{"key":"2026052808150955000_12.2.e006828.5","doi-asserted-by":"publisher","DOI":"10.1002\/art.27584"},{"key":"2026052808150955000_12.2.e006828.6","doi-asserted-by":"crossref","first-page":"152251","DOI":"10.1016\/j.semarthrit.2023.152251","article-title":"Disentangling heterogeneity in contemporary undifferentiated arthritis \u2013 A large cohort study using latent class analysis","volume":"63","author":"den Hollander","year":"2023","journal-title":"Semin Arthritis Rheum"},{"key":"2026052808150955000_12.2.e006828.7","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-203165"},{"key":"2026052808150955000_12.2.e006828.8","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.119016"},{"key":"2026052808150955000_12.2.e006828.9","doi-asserted-by":"publisher","DOI":"10.1002\/art.22525"},{"key":"2026052808150955000_12.2.e006828.10","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.084269"},{"key":"2026052808150955000_12.2.e006828.11","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keab880"},{"key":"2026052808150955000_12.2.e006828.12","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210094"},{"key":"2026052808150955000_12.2.e006828.13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1507247"},{"key":"2026052808150955000_12.2.e006828.14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1608345"},{"key":"2026052808150955000_12.2.e006828.15","doi-asserted-by":"crossref","DOI":"10.1186\/s13063-024-08609-5","article-title":"Induction of Cure in Early Arthritis (I CEA): study protocol for an investigator-initiated randomized single-blind clinical trial with open-label extension to compare three treatment strategies in patients with newly diagnosed undifferentiated arthritis","volume":"25","author":"Bergstra","year":"2024","journal-title":"Trials"},{"key":"2026052808150955000_12.2.e006828.16","doi-asserted-by":"publisher","DOI":"10.1002\/pst.291"},{"key":"2026052808150955000_12.2.e006828.17","doi-asserted-by":"publisher","DOI":"10.1002\/acr.20621"},{"key":"2026052808150955000_12.2.e006828.18","first-page":"280","article-title":"Determining the minimal clinically important differences in activity, fatigue, and sleep quality in patients with rheumatoid arthritis","volume":"34","author":"Wells","year":"2007","journal-title":"J Rheumatol"},{"key":"2026052808150955000_12.2.e006828.19","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.080375"},{"key":"2026052808150955000_12.2.e006828.20","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/acr.22583","article-title":"Distinctions between diagnostic and classification criteria?","volume":"67","author":"Aggarwal","year":"2015","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"2026052808150955000_12.2.e006828.21","unstructured":"Agency EM . Janus kinase inhibitors (jaki): european medicines agency. n.d. Available: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/referrals\/janus-kinase-inhibitors-jaki"}],"container-title":["RMD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rmdopen-2026-006828","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T15:15:21Z","timestamp":1779981321000},"score":1,"resource":{"primary":{"URL":"https:\/\/rmdopen.bmj.com\/lookup\/doi\/10.1136\/rmdopen-2026-006828"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":21,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,5,28]]},"published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1136\/rmdopen-2026-006828"],"URL":"https:\/\/doi.org\/10.1136\/rmdopen-2026-006828","relation":{},"ISSN":["2056-5933"],"issn-type":[{"value":"2056-5933","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]}}}