{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T20:43:26Z","timestamp":1793479406308,"version":"4.5.0"},"reference-count":28,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"unspecified","delay-in-days":19,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["Programma Translationeel Onderzoek"],"award-info":[{"award-number":["Programma Translationeel Onderzoek"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018286","name":"Dutch Arthritis Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018286","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,12,31]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The TREAT EARLIER trial showed in clinically suspect arthralgia (CSA) that methotrexate induced reductions in subclinical inflammation and related disease burden during the year of treatment, which was sustained thereafter. We studied whether the treatment response defined at the level of subclinical joint inflammation was present in all treated CSA patients and, if not, what characterises the subgroup of responders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CSA patients with subclinical inflammation were randomised to receive an intramuscular glucocorticoid injection and a 1-year course of methotrexate. Treatment response was defined as a reduction of MRI-detected synovitis, tenosynovitis or osteitis levels beyond the smallest detectable change at 12\u2009months. Baseline clinical and imaging characteristics were studied in relation to treatment response. Predictive values were determined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>44 of 115 (38%) treated patients had an MRI-defined treatment response. These patients also significantly improved in pain and physical functioning (\u221222 Visual Analogue Scale pain, \u22120.29 Health Assessment Questionnaire). Baseline clinical variables were not independently associated with this response, in contrast to the severity of subclinical joint inflammation. Tenosynovitis and osteitis levels in particular were predictive. Patients with \u22652 sites with tenosynovitis or a combination of osteitis and tenosynovitis (with \u22651 of these features at \u22652 sites) had high positive predictive values (PPV 77%, 79%). PPVs were similar in ACPA-positive and ACPA-negative patients at increased risk for rheumatoid arthritis (RA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CSA patients with subclinical inflammation who responded best to methotrexate during the first year were identified by increased levels of subclinical inflammation at diagnosis, primarily due to multiple sites of tenosynovitis with\/without osteitis. These data may contribute to personalised medicine for arthralgia at risk for RA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2025-006102","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T19:16:17Z","timestamp":1769627777000},"page":"e006102","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Which arthralgia patients benefit most in reduction of subclinical joint inflammation by methotrexate treatment: results from the TREAT EARLIER trial"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6299-7653","authenticated-orcid":false,"given":"Stijn","family":"Claassen","sequence":"first","affiliation":[{"name":"Rheumatology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0318-096X","authenticated-orcid":false,"given":"Quirine A","family":"Dumoulin","sequence":"additional","affiliation":[{"name":"Rheumatology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman K","family":"Glas","sequence":"additional","affiliation":[{"name":"Rheumatology, Reumazorg Zuid West Nederland, Goes, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esmeralda","family":"Molenaar","sequence":"additional","affiliation":[{"name":"Rheumatology, Groene Hart Hospital, Gouda, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3251-0238","authenticated-orcid":false,"given":"Hanna W","family":"van Steenbergen","sequence":"additional","affiliation":[{"name":"Rheumatology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8572-1437","authenticated-orcid":false,"given":"Annette HM","family":"van der Helm - van Mil","sequence":"additional","affiliation":[{"name":"Rheumatology, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"Rheumatology, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"2026012811161117000_12.1.e006102.1","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2016-000419","article-title":"Functional limitations in the phase of clinically suspect arthralgia are as serious as in early clinical arthritis; a longitudinal study","volume":"3","author":"Ten Brinck","year":"2017","journal-title":"RMD Open"},{"key":"2026012811161117000_12.1.e006102.2","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2021-002128","article-title":"The value of MRI for detecting subclinical joint inflammation in clinically suspect arthralgia","volume":"8","author":"Boeren","year":"2022","journal-title":"RMD Open"},{"key":"2026012811161117000_12.1.e006102.3","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-220750"},{"key":"2026012811161117000_12.1.e006102.4","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-216243"},{"key":"2026012811161117000_12.1.e006102.5","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1093\/rheumatology\/keab793","article-title":"Work participation is reduced during the development of RA, months before clinical arthritis manifests","volume":"61","author":"Rogier","year":"2022","journal-title":"Rheumatology (Oxford)"},{"key":"2026012811161117000_12.1.e006102.6","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1093\/rheumatology\/keab651","article-title":"Morning stiffness precedes the development of rheumatoid arthritis and associates with systemic and subclinical joint inflammation in arthralgia patients","volume":"61","author":"Krijbolder","year":"2022","journal-title":"Rheumatology (Oxford)"},{"key":"2026012811161117000_12.1.e006102.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-023-01035-y"},{"key":"2026012811161117000_12.1.e006102.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01193-X"},{"key":"2026012811161117000_12.1.e006102.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)02649-1"},{"key":"2026012811161117000_12.1.e006102.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)02650-8"},{"key":"2026012811161117000_12.1.e006102.11","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1136\/ard-2024-226286","article-title":"Is a 1-year course of methotrexate in patients with arthralgia at-risk for rheumatoid arthritis cost-effective? 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Which arthralgia patients at risk for ra benefited from treatment with methotrexate?; results from the TREAT EARLIER trial. 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