{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:43:04Z","timestamp":1790628184420,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,3,31]],"date-time":"2017-03-31T00:00:00Z","timestamp":1490918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007949","name":"Swedish Rheumatism Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007949","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Schering-Plough Sweden"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate whether the Multi\u2010Biomarker Disease Activity (MBDA) score predicts optimal add\u2010on treatment in patients with early rheumatoid arthritis (RA) who were inadequate responders to MTX (MTX\u2010IRs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed data from 157 MTX\u2010IRs (with a Disease Activity Score using the erythrocyte sedimentation rate [DAS28\u2010ESR] &gt;3.2) from the Swedish Pharmacotherapy (SWEFOT) trial who were randomized to receive triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) versus MTX plus infliximab. The MBDA score as a predictor of the subsequent DAS28\u2010based response to each second\u2010line treatment was analyzed at randomization with the Breslow\u2010Day test for 2 \u00d7 2 groups, using both validated categories (low [&lt;30], moderate [30\u201344], and high [&gt;44]) and dichotomized categories (lower [\u226438] versus higher [&gt;38]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 157 patients, 12% had a low MBDA score, 32% moderate, and 56% high. Of those with a low MBDA score, 88% responded to subsequent triple therapy, and 18% responded to MTX plus infliximab (<jats:italic>P<\/jats:italic>\u2009=\u20090.006); for those with a high MBDA score, the response rates were 35% and 58%, respectively (<jats:italic>P<\/jats:italic>\u2009=\u20090.040). When using 38 as a cutoff for the MBDA score (29% patients with lower scores versus 71% with higher scores), the differential associations with response to triple therapy versus MTX plus infliximab were 79% versus 44% and 36% versus 58%, respectively (<jats:italic>P<\/jats:italic>\u2009=\u20090.001). Clinical and inflammatory markers had poorer predictive capacity for response to triple therapy or MTX plus infliximab.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In patients with RA who had an inadequate response to MTX, the MBDA score categories were differentially associated with response to subsequent therapies. Thus, patients with post\u2010MTX biochemical improvements (lower MBDA scores) were more likely to respond to triple therapy than to MTX plus infliximab. If confirmed, these results may help to improve treatment in RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40019","type":"journal-article","created":{"date-parts":[[2016,12,19]],"date-time":"2016-12-19T16:18:47Z","timestamp":1482164327000},"page":"953-963","source":"Crossref","is-referenced-by-count":28,"title":["A Multi\u2010Biomarker Disease Activity Score and the Choice of Second\u2010Line Therapy in Early Rheumatoid Arthritis After Methotrexate Failure"],"prefix":"10.1002","volume":"69","author":[{"given":"Karen","family":"Hambardzumyan","sequence":"first","affiliation":[{"name":"Karolinska Institutet, Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saedis","family":"Saevarsdottir","sequence":"additional","affiliation":[{"name":"Karolinska Institutet, Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Forslind","sequence":"additional","affiliation":[{"name":"Lund University and Helsingborg's Lasarett Helsingborg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingemar F.","family":"Petersson","sequence":"additional","affiliation":[{"name":"Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan K.","family":"Wallman","sequence":"additional","affiliation":[{"name":"Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Ernestam","sequence":"additional","affiliation":[{"name":"Institution LIME Medical Management Centre, Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J.","family":"Bolce","sequence":"additional","affiliation":[{"name":"Crescendo Bioscience, Inc. South San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald F.","family":"van Vollenhoven","sequence":"additional","affiliation":[{"name":"Karolinska Institutet, Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204573"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39480"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199605163342002"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10228"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204788"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)05246-0"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60944-2"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203497"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34498"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1303006"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-205060"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.131401"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.139212"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kes084"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-14-153"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060635"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21767"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60027-0"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204986"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780390105"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199810)41:10<1845::AID-ART17>3.0.CO;2-K"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2012.06.003"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200038"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11481"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20222"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2011.154625"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.149260"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2015-000197"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.093153"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2008.03691.x"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3188"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2706"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/anr.1780320916"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep090"}],"container-title":["Arthritis &amp; 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