{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:06:15Z","timestamp":1788527175649,"version":"build-2803163510"},"reference-count":39,"publisher":"BMJ","issue":"1","funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2018,2,8]]},"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To evaluate the effects of the T-cell costimulation blocker abatacept on anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) in early rheumatoid arthritis (RA), and associations between changes in serological status and clinical response.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Post hoc analysis of the phase III AGREE study in methotrexate (MTX)-na\u00efve patients with early RA and poor prognostic factors. Patients were randomised to abatacept (~10\u2009mg\/kg intravenously according to weight range) or placebo, plus MTX over 12 months followed by open-label abatacept plus MTX for 12 months. Autoantibody titres were determined by ELISA at baseline and months 6 and 12 (double-blind phase). Conversion to seronegative status and its association with clinical response were assessed at months 6 and 12.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Abatacept plus MTX was associated with a greater decrease in ACPA (but not RF) titres and higher rates of both ACPA and RF conversion to seronegative status versus MTX alone. More patients converting to ACPA seronegative status receiving abatacept plus MTX achieved remission according to Disease Activity Score in 28 joints (C-reactive protein) or Clinical Disease Activity Index than patients who remained ACPA seropositive. Patients who converted to ACPA seronegative status treated with abatacept plus MTX had a greater probability of achieving sustained remission and less radiographic progression than MTX alone or patients who remained ACPA seropositive (either treatment).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Treatment with abatacept plus MTX was more likely to induce conversion to ACPA\/RF seronegative status in patients with early, erosive RA. Conversion to ACPA seronegative status was associated with better clinical and radiographic outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"NCT00122382\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial pre-results\">NCT00122382<\/jats:ext-link>\n                  <\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2017-000564","type":"journal-article","created":{"date-parts":[[2018,3,30]],"date-time":"2018-03-30T08:20:14Z","timestamp":1522398014000},"page":"e000564","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":43,"title":["Conversion to seronegative status after abatacept treatment in patients with early and poor prognostic rheumatoid arthritis is associated with better radiographic outcomes and sustained remission: post hoc analysis of the AGREE study"],"prefix":"10.1136","volume":"4","clinical-trial-number":[{"clinical-trial-number":"nct00122382","registry":"10.18810\/clinical-trials-gov","type":"preResults"},{"clinical-trial-number":"nct00122382","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4535-9167","authenticated-orcid":false,"given":"Diahann T S L","family":"Jansen","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Emery","sequence":"additional","affiliation":[{"name":"Leeds Musculoskeletal Biomedical Research Unit, LTHT Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef S","family":"Smolen","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene","family":"Westhovens","sequence":"additional","affiliation":[{"name":"Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium"},{"name":"Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Le Bars","sequence":"additional","affiliation":[{"name":"Medical Affairs, Bristol-Myers Squibb, Rueil-Malmaison, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean E","family":"Connolly","sequence":"additional","affiliation":[{"name":"US Medical, Bristol-Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June","family":"Ye","sequence":"additional","affiliation":[{"name":"Global Biometric Sciences, Bristol-Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9 E M","family":"Toes","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom W J","family":"Huizinga","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2018,3,30]]},"reference":[{"key":"2025090313505196000_4.1.e000564.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60826-4"},{"key":"2025090313505196000_4.1.e000564.2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1316"},{"key":"2025090313505196000_4.1.e000564.3","doi-asserted-by":"crossref","first-page":"304","DOI":"10.3109\/07853890.2014.907097","article-title":"HLA and rheumatoid arthritis: how do they connect?","volume":"46","author":"van Heemst","year":"2014","journal-title":"Ann Med"},{"key":"2025090313505196000_4.1.e000564.4","first-page":"1282","article-title":"Rheumatoid factors antedating clinical rheumatoid arthritis","volume":"18","author":"Aho","year":"1991","journal-title":"J Rheumatol"},{"key":"2025090313505196000_4.1.e000564.5","first-page":"1278","article-title":"Antikeratin antibody and antiperinuclear factor as markers for subclinical rheumatoid disease process","volume":"20","author":"Aho","year":"1993","journal-title":"J Rheumatol"},{"key":"2025090313505196000_4.1.e000564.6","doi-asserted-by":"publisher","DOI":"10.1002\/art.20018"},{"key":"2025090313505196000_4.1.e000564.7","doi-asserted-by":"publisher","DOI":"10.1002\/art.11223"},{"key":"2025090313505196000_4.1.e000564.8","doi-asserted-by":"publisher","DOI":"10.1002\/art.30537"},{"key":"2025090313505196000_4.1.e000564.9","doi-asserted-by":"publisher","DOI":"10.1186\/ar2704"},{"key":"2025090313505196000_4.1.e000564.10","doi-asserted-by":"publisher","DOI":"10.1186\/ar1767"},{"key":"2025090313505196000_4.1.e000564.11","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205428"},{"key":"2025090313505196000_4.1.e000564.12","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0736-9"},{"key":"2025090313505196000_4.1.e000564.13","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204543"},{"key":"2025090313505196000_4.1.e000564.14","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121486"},{"key":"2025090313505196000_4.1.e000564.15","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780280302"},{"key":"2025090313505196000_4.1.e000564.16","doi-asserted-by":"publisher","DOI":"10.1002\/art.25036"},{"key":"2025090313505196000_4.1.e000564.17","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780280704"},{"key":"2025090313505196000_4.1.e000564.18","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-206598"},{"key":"2025090313505196000_4.1.e000564.19","doi-asserted-by":"publisher","DOI":"10.1002\/art.21385"},{"key":"2025090313505196000_4.1.e000564.20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2009.00780.x"},{"key":"2025090313505196000_4.1.e000564.21","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1989"},{"key":"2025090313505196000_4.1.e000564.22","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050524"},{"key":"2025090313505196000_4.1.e000564.23","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa035075"},{"key":"2025090313505196000_4.1.e000564.24","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.119016"},{"key":"2025090313505196000_4.1.e000564.25","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-206106"},{"key":"2025090313505196000_4.1.e000564.26","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.139345"},{"key":"2025090313505196000_4.1.e000564.27","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.130263"},{"key":"2025090313505196000_4.1.e000564.28","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.145268"},{"key":"2025090313505196000_4.1.e000564.29","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.101121"},{"key":"2025090313505196000_4.1.e000564.30","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0671-9"},{"key":"2025090313505196000_4.1.e000564.31","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202297"},{"key":"2025090313505196000_4.1.e000564.32","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/s13075-015-0731-1","article-title":"Abatacept decreases disease activity in a absence of CD4(+) T cells in a collagen-induced arthritis model","volume":"17","author":"Jansen","year":"2015","journal-title":"Arthritis Res Ther"},{"key":"2025090313505196000_4.1.e000564.33","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110040"},{"key":"2025090313505196000_4.1.e000564.34","doi-asserted-by":"publisher","DOI":"10.1002\/art.37787"},{"key":"2025090313505196000_4.1.e000564.35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/art.39480","article-title":"2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis","volume":"68","author":"Singh","year":"2016","journal-title":"Arthritis Rheumatol"},{"key":"2025090313505196000_4.1.e000564.36","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204573"},{"key":"2025090313505196000_4.1.e000564.37","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-208258"},{"key":"2025090313505196000_4.1.e000564.38","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203565"},{"issue":"Suppl 2","key":"2025090313505196000_4.1.e000564.39","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1136\/annrheumdis-2014-eular.2469","article-title":"Modulation of the ACPA fine specificity in patients with RA treated with either abatacept or adalimumab in the AMPLE study","volume":"73","author":"Connolly","year":"2014","journal-title":"Ann Rheum Dis"}],"container-title":["RMD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rmdopen-2017-000564","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T20:50:57Z","timestamp":1756932657000},"score":1,"resource":{"primary":{"URL":"https:\/\/rmdopen.bmj.com\/lookup\/doi\/10.1136\/rmdopen-2017-000564"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,3,30]]},"published-print":{"date-parts":[[2018,3]]}},"alternative-id":["10.1136\/rmdopen-2017-000564"],"URL":"https:\/\/doi.org\/10.1136\/rmdopen-2017-000564","relation":{},"ISSN":["2056-5933"],"issn-type":[{"value":"2056-5933","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3]]}}}