{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T06:12:17Z","timestamp":1793686337018,"version":"4.5.1"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T00:00:00Z","timestamp":1578873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"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":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis Care & Research"],"published-print":{"date-parts":[[2020,2]]},"abstract":"Objective<\/jats:title>Seropositivity for anti\u2013citrullinated protein antibody (ACPA<\/jats:styled-content>)\/rheumatoid factor (RF<\/jats:styled-content>) in rheumatoid arthritis (RA<\/jats:styled-content>) is associated with increased overall mortality; however, the association between antibody titers and mortality is not well established. Investigating relationships between antibody titers and mortality may clarify their role in RA<\/jats:styled-content> pathogenesis. This study was undertaken to evaluate the association of antibody titers with mortality and its modification by disease\u2010modifying antirheumatic drugs (DMARD<\/jats:styled-content>s).<\/jats:p><\/jats:sec>Methods<\/jats:title>Eligible patients with established RA<\/jats:styled-content> were identified through administrative claims data linked to laboratory results (2005\u20132016). Patients were categorized by positivity status for ACPA<\/jats:styled-content>, RF<\/jats:styled-content>, or both. Patients were further divided into groups by autoantibody titers. DMARD<\/jats:styled-content>\u2010exposed patients were categorized into biologic DMARD<\/jats:styled-content> (bDMARD<\/jats:styled-content>) and conventional DMARD<\/jats:styled-content> (cDMARD<\/jats:styled-content>) subcohorts. Crude mortality rates\/1,000 patient\u2010years and Kaplan\u2010Meier curves were compared between antibody categories. Adjusted Cox proportional hazards regression and sensitivity (propensity\u2010matched patients) analyses were conducted.<\/jats:p><\/jats:sec>Results<\/jats:title>Overall, 53,849 and 79,926 patients had evaluable ACPA<\/jats:styled-content> and RF<\/jats:styled-content> status, respectively. For both autoantibodies, mortality rates were significantly higher in seropositive versus seronegative patients (risk increase of 48.0% and 44.0% in ACPA<\/jats:styled-content>\u2010 and RF<\/jats:styled-content>\u2010positive patients, respectively; P<\/jats:italic> < 0.001 each). Mortality rates were greatest in patients with higher versus lower autoantibody titers (ACPA<\/jats:styled-content> hazard ratio [HR<\/jats:styled-content>] 1.60 [95% confidence interval (95% CI<\/jats:styled-content>]) 1.45\u20131.76]; RF HR<\/jats:styled-content> 1.78 [95% CI<\/jats:styled-content> 1.66\u20131.91]). In cDMARD<\/jats:styled-content>\u2010exposed patients, HR<\/jats:styled-content>s were higher in seropositive versus seronegative cohorts; in bDMARD<\/jats:styled-content>\u2010exposed patients, there was no difference in mortality by serostatus.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Elevated ACPA<\/jats:styled-content>\/RF<\/jats:styled-content> titers were independently associated with increased mortality among patients with RA<\/jats:styled-content> and persisted in patients treated with cDMARD<\/jats:styled-content>s but not with bDMARD<\/jats:styled-content>s.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr.24071","type":"journal-article","created":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T07:13:02Z","timestamp":1568704382000},"page":"176-183","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Association of Seropositivity and Mortality in Rheumatoid Arthritis and the Impact of Treatment With Disease\u2010Modifying Antirheumatic Drugs: Results From a Real\u2010World Study"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9292-9420","authenticated-orcid":false,"given":"Evo","family":"Alemao","sequence":"first","affiliation":[{"name":"Bristol\u2010Myers Squibb Princeton New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Bao","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb Princeton New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Weinblatt","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Shadick","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60826-4"},{"key":"e_1_2_7_3_1","first-page":"1282","article-title":"Rheumatoid factors antedating clinical rheumatoid arthritis","volume":"18","author":"Aho K","year":"1991","journal-title":"J Rheumatol"},{"key":"e_1_2_7_4_1","first-page":"1278","article-title":"Antikeratin antibody and antiperinuclear factor as markers for subclinical rheumatoid disease process","volume":"20","author":"Aho K","year":"1993","journal-title":"J Rheumatol"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20018"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11223"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30537"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210715"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3109\/07853890.2014.907097"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1767"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0736-9"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27584"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39480"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780270805"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)91672-2"},{"issue":"51","key":"e_1_2_7_16_1","first-page":"S35","article-title":"Mortality in rheumatoid arthritis: 2008 update","volume":"26","author":"Sokka T","year":"2008","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.148759"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket301"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202958"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205428"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2017-000564"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2003.014647"},{"key":"e_1_2_7_23_1","first-page":"1972","article-title":"Differential response of the rheumatoid factor and anticitrullinated protein antibodies during adalimumab treatment in patients with rheumatoid arthritis","volume":"35","author":"Bos WH","year":"2008","journal-title":"J Rheumatol"},{"key":"e_1_2_7_24_1","unstructured":"ICD9Data.com.Rheumatoid arthritis and other inflammatory polyarthropathies.2018. 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