{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T11:26:12Z","timestamp":1788002772466,"version":"build-2784847793"},"reference-count":47,"publisher":"The Journal of Rheumatology","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:sec><jats:title>Objective.<\/jats:title><jats:p>To investigate baseline levels of 12 serum biomarkers that constitute a multibiomarker disease activity test, as predictors of response to methotrexate (MTX) in patients with early rheumatoid arthritis (eRA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>In 298 patients from the Swedish Pharmacotherapy (SWEFOT) clinical trial, baseline serum levels of 12 proteins were analyzed for association with disease activity based on the 28-joint count Disease Activity Score (DAS28) after 3 months of MTX monotherapy using uni-\/multivariate logistic regression. Primary outcome was low disease activity (LDA; DAS28 \u2264 3.2).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>Of 298 patients, 104 achieved LDA after 3 months on MTX. Four of the 12 biomarkers [C-reactive protein (CRP), leptin, tumor necrosis factor receptor I (TNF-RI), and vascular cell adhesion molecule 1 (VCAM-1)] significantly predicted LDA based on stepwise logistic regression analysis. Dichotomization of patients using receiver-operating characteristic curve analysis-based cutoffs for these biomarkers showed significantly higher proportions with LDA among patients with lower versus higher levels of CRP or leptin (40% vs 23%, p = 0.004, and 40% vs 25%, p = 0.011, respectively), as well as among those with higher versus lower levels of TNF-RI or VCAM-1 (43% vs 27%, p = 0.004, and 41% vs 25%, p = 0.004, respectively). Combined score based on these biomarkers, adjusted for known predictors of LDA (smoking, sex, and age), associated with decreased chance of LDA (adjusted OR 0.45, 95% CI 0.32\u20130.62).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion.<\/jats:title><jats:p>Low baseline levels of CRP and leptin, and high baseline levels of TNF-RI and VCAM-1 were associated with LDA after 3 months of MTX therapy in patients with eRA. Combination of these 4 biomarkers increased accuracy of prediction. [Trial registration number: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT00764725\">NCT00764725<\/jats:ext-link>]<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.180537","type":"journal-article","created":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T12:42:44Z","timestamp":1549024964000},"page":"555-563","source":"Crossref","is-referenced-by-count":19,"title":["Serum Biomarkers for Prediction of Response to Methotrexate Monotherapy in Early Rheumatoid Arthritis: Results from the SWEFOT Trial"],"prefix":"10.3899","volume":"46","author":[{"given":"Karen","family":"Hambardzumyan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J.","family":"Bolce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4915-2924","authenticated-orcid":false,"given":"Johan K.","family":"Wallman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6438-8663","authenticated-orcid":false,"given":"Ronald F.","family":"van Vollenhoven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9392-6184","authenticated-orcid":false,"given":"Saedis","family":"Saevarsdottir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2262","published-online":{"date-parts":[[2019,2,1]]},"reference":[{"key":"2019061118352006000_46.6.555.1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204573"},{"key":"2019061118352006000_46.6.555.2","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21641"},{"key":"2019061118352006000_46.6.555.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60944-2"},{"key":"2019061118352006000_46.6.555.4","first-page":"11","article-title":"Factors influencing response to disease modifying antirheumatic drugs in patients with rheumatoid arthritis","volume":"32","author":"Hider","year":"2005","journal-title":"J Rheumatol"},{"key":"2019061118352006000_46.6.555.5","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.088237"},{"key":"2019061118352006000_46.6.555.6","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.090838"},{"key":"2019061118352006000_46.6.555.7","doi-asserted-by":"crossref","first-page":"377","DOI":"10.2217\/pgs.12.13","article-title":"The challenges of methotrexate pharmacogenetics in rheumatoid arthritis","volume":"13","author":"Ranganathan","year":"2012","journal-title":"Pharmacogenomics"},{"key":"2019061118352006000_46.6.555.8","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep112"},{"key":"2019061118352006000_46.6.555.9","doi-asserted-by":"publisher","DOI":"10.1002\/art.22640"},{"key":"2019061118352006000_46.6.555.10","doi-asserted-by":"publisher","DOI":"10.1136\/ard.62.5.423"},{"key":"2019061118352006000_46.6.555.11","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.139212"},{"key":"2019061118352006000_46.6.555.12","doi-asserted-by":"publisher","DOI":"10.1002\/art.27758"},{"key":"2019061118352006000_46.6.555.13","first-page":"861","article-title":"Does cigarette smoking influence disease expression, activity and severity in early rheumatoid arthritis patients?","volume":"23","author":"Papadopoulos","year":"2005","journal-title":"Clin Exp Rheumatol"},{"key":"2019061118352006000_46.6.555.14","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kei240"},{"key":"2019061118352006000_46.6.555.15","doi-asserted-by":"publisher","DOI":"10.1136\/ard.56.8.463"},{"key":"2019061118352006000_46.6.555.16","first-page":"630","article-title":"The effect of smoking on clinical, laboratory, and radiographic status in rheumatoid arthritis","volume":"27","author":"Wolfe","year":"2000","journal-title":"J Rheumatol"},{"key":"2019061118352006000_46.6.555.17","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200001)43:1<22::AID-ANR4>3.0.CO;2-9"},{"key":"2019061118352006000_46.6.555.18","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.110169"},{"key":"2019061118352006000_46.6.555.19","doi-asserted-by":"publisher","DOI":"10.1002\/art.22943"},{"key":"2019061118352006000_46.6.555.20","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.jbspin.2010.02.018","article-title":"Prediction of response to disease modifying antirheumatic drugs in rheumatoid arthritis","volume":"77","author":"Maillefert","year":"2010","journal-title":"Joint Bone Spine"},{"key":"2019061118352006000_46.6.555.21","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13075-016-0919-z","article-title":"Higher expression of TNF\u03b1-induced genes in the synovium of patients with early rheumatoid arthritis correlates with disease activity, and predicts absence of response to first line therapy","volume":"18","author":"De Groof","year":"2016","journal-title":"Arthritis Res Ther"},{"key":"2019061118352006000_46.6.555.22","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1111\/1756-185X.12380","article-title":"High serum level of haptoglobin is associated with the response of 12 weeks methotrexate therapy in recent-onset rheumatoid arthritis patients","volume":"19","author":"Tan","year":"2016","journal-title":"Int J Rheum Dis"},{"key":"2019061118352006000_46.6.555.23","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.150998"},{"key":"2019061118352006000_46.6.555.24","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204986"},{"key":"2019061118352006000_46.6.555.25","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2015-000197"},{"key":"2019061118352006000_46.6.555.26","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1002\/art.40019","article-title":"A multi-biomarker disease activity score and the choice of second-line therapy in early rheumatoid arthritis after methotrexate failure","volume":"69","author":"Hambardzumyan","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"2019061118352006000_46.6.555.27","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780390105"},{"key":"2019061118352006000_46.6.555.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2012.06.003"},{"key":"2019061118352006000_46.6.555.29","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-eular.1187"},{"key":"2019061118352006000_46.6.555.30","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kes378"},{"key":"2019061118352006000_46.6.555.31","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.131412"},{"key":"2019061118352006000_46.6.555.32","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21767"},{"key":"2019061118352006000_46.6.555.33","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200963"},{"key":"2019061118352006000_46.6.555.34","first-page":"231","article-title":"Prognostic markers of clinical remission in early rheumatoid arthritis after two years of DMARDs in a clinical setting","volume":"25","author":"Vazquez","year":"2007","journal-title":"Clin Exp Rheumatol"},{"key":"2019061118352006000_46.6.555.35","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2003.010611"},{"key":"2019061118352006000_46.6.555.36","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.52.1.339"},{"key":"2019061118352006000_46.6.555.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2007.09.004"},{"key":"2019061118352006000_46.6.555.38","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-011-2182-6"},{"key":"2019061118352006000_46.6.555.39","doi-asserted-by":"crossref","first-page":"e00205","DOI":"10.1016\/j.heliyon.2016.e00205","article-title":"Absence of a positive correlation between CRP and leptin in rheumatoid arthritis","volume":"2","author":"Najafizadeh","year":"2016","journal-title":"Heliyon"},{"key":"2019061118352006000_46.6.555.40","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040435"},{"key":"2019061118352006000_46.6.555.41","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.5.2911"},{"key":"2019061118352006000_46.6.555.42","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/j.1749-6632.1998.tb11153.x","article-title":"Activation and methotrexate-mediated suppression of the TNF alpha promoter in T cells and macrophages","volume":"859","author":"Becker","year":"1998","journal-title":"Ann N Y Acad Sci"},{"key":"2019061118352006000_46.6.555.43","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.01022.x"},{"key":"2019061118352006000_46.6.555.44","doi-asserted-by":"publisher","DOI":"10.1136\/ard.59.4.311"},{"key":"2019061118352006000_46.6.555.45","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/37.5.502"},{"key":"2019061118352006000_46.6.555.46","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200008)43:8<1820::AID-ANR18>3.0.CO;2-D"},{"key":"2019061118352006000_46.6.555.47","doi-asserted-by":"publisher","DOI":"10.1080\/03009740701406460"}],"container-title":["The Journal of Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.3899\/jrheum.180537","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,6,11]],"date-time":"2019-06-11T21:35:59Z","timestamp":1560288959000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.jrheum.org\/lookup\/doi\/10.3899\/jrheum.180537"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,1]]},"references-count":47,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,6,1]]},"published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.3899\/jrheum.180537"],"URL":"https:\/\/doi.org\/10.3899\/jrheum.180537","relation":{},"ISSN":["0315-162X","1499-2752"],"issn-type":[{"value":"0315-162X","type":"print"},{"value":"1499-2752","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,1]]}}}