{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:13:14Z","timestamp":1791666794464,"version":"4.3.4"},"reference-count":188,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Rheumatoid factor (RF) is the first autoantibody identified in rheumatoid arthritis (RA) which targets the fragment crystallizable (Fc) region of immunoglobulin (Ig) G. Although IgM isotype is predominant, other Ig isotypes, including IgG and IgA, also exist. While RF is not specific to RA, it remains a valuable serological test for diagnosing the disease, as evidenced by its inclusion in the 2010 classification criteria for RA based on elevated serum RF levels. RF is also associated with RA severity, including joint damage and extra-articular manifestations, serving as a poor prognostic factor and aiding in the identification of difficult-to-treat RA. Recent studies have demonstrated that high serum RF levels are associated with a reduced response to tumor necrosis factor (TNF) inhibitors. In contrast, anti-TNF antibodies lacking the Fc portion have shown stable efficacy in RA patients regardless of baseline RF levels. These findings reaffirm the clinical significance of RF measurement, 80 years after its initial discovery. This review explores the diagnostic and prognostic significance of RF and its impact on treatment selection in RA management.<\/jats:p>","DOI":"10.3390\/jcm14051529","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T03:40:12Z","timestamp":1740454812000},"page":"1529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Rheumatoid Factor: Diagnostic and Prognostic Performance and Therapeutic Implications in Rheumatoid Arthritis"],"prefix":"10.3390","volume":"14","author":[{"given":"Tasuku","family":"Togashi","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuhei","family":"Ishihara","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1089-5296","authenticated-orcid":false,"given":"Ryu","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8992-1805","authenticated-orcid":false,"given":"Mayu","family":"Shiomi","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Yano","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1718-0752","authenticated-orcid":false,"given":"Yuhei","family":"Fujisawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0033-1757","authenticated-orcid":false,"given":"Masao","family":"Katsushima","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8576-5816","authenticated-orcid":false,"given":"Kazuo","family":"Fukumoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motomu","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18001","DOI":"10.1038\/nrdp.2018.1","article-title":"Rheumatoid arthritis","volume":"4","author":"Smolen","year":"2018","journal-title":"Nat. Rev. Dis. Primers."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1126\/science.3047874","article-title":"Symmetrical erosive peripheral polyarthritis in the Late Archaic Period of Alabama","volume":"241","author":"Rothschild","year":"1988","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s00296-020-04731-0","article-title":"The global prevalence of rheumatoid arthritis: A meta-analysis based on a systematic review","volume":"41","author":"Almutairi","year":"2021","journal-title":"Rheumatol. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1136\/ard.2010.138461","article-title":"2010 rheumatoid arthritis classification criteria: An American College of Rheumatology\/European League Against Rheumatism collaborative initiative","volume":"69","author":"Aletaha","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4590","DOI":"10.1093\/rheumatology\/keac261","article-title":"Musculoskeletal ultrasound for treating rheumatoid arthritis to target\u2014A systematic literature review","volume":"61","author":"Silvagni","year":"2022","journal-title":"Rheumatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.berh.2017.10.006","article-title":"Magnetic resonance imaging in individuals at risk of rheumatoid arthritis","volume":"31","author":"Hunt","year":"2017","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1097\/BOR.0000000000001006","article-title":"Autoantibodies in rheumatoid arthritis\u2014Rheumatoid factor, anticitrullinated protein antibodies and beyond","volume":"36","author":"Steiner","year":"2024","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1111\/j.1600-0463.2007.apm_682a.x","article-title":"On the occurrence of a factor in human serum activating the specific agglutintion of sheep blood corpuscles","volume":"115","author":"Waaler","year":"2007","journal-title":"APMIS"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"441","DOI":"10.4049\/jimmunol.63.4.441","article-title":"Serological reactions in rheumatoid arthritis; factors affecting the agglutination of sensitized sheep erythrocytes in rheumatid-arthritis serum","volume":"63","author":"Pike","year":"1949","journal-title":"J. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1080\/08916930400022574","article-title":"Rheumatoid factor on a daily basis","volume":"38","author":"Renaudineau","year":"2005","journal-title":"Autoimmunity"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13075-016-0940-2","article-title":"Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis","volume":"18","author":"Brink","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_12","unstructured":"(2025, February 17). WHO Reference Reagent Rheumatoid Arthritis Serum, Human NIBSC Code: W1066 Instructions for Use (Version 2.0, Dated 04\/04\/2008). Available online: https:\/\/nibsc.org\/documents\/ifu\/W1066.pdf."},{"key":"ref_13","unstructured":"(2025, February 17). Non WHO Reference Material Rheumatoid Arthritis Serum, 1st British Standard NIBSC Code: 64\/002 Instructions for Use (Version 6.0, Dated 04\/04\/2008). Available online: https:\/\/www.nibsc.org\/documents\/ifu\/64-002.pdf."},{"key":"ref_14","first-page":"311","article-title":"International reference preparation of rheumatoid arthritis serum","volume":"42","author":"Anderson","year":"1970","journal-title":"Bull. World Health Organ."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1515\/cclm-2022-0244","article-title":"IgA rheumatoid factor in rheumatoid arthritis","volume":"60","author":"Sieghart","year":"2022","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e002099","DOI":"10.1136\/rmdopen-2021-002099","article-title":"Multicentre study to improve clinical interpretation of rheumatoid factor and anti-citrullinated protein\/peptide antibodies test results","volume":"8","author":"Sieghart","year":"2022","journal-title":"RMD Open"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1136\/ard.46.1.65","article-title":"IgM rheumatoid factor (RF), IgA RF, IgE RF, and IgG RF detected by ELISA in rheumatoid arthritis","volume":"46","author":"Auvinet","year":"1987","journal-title":"Ann. Rheum. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/S0307-742X(21)00604-4","article-title":"IgG rheumatoid factors and self-association of these antibodies","volume":"11","author":"Mannik","year":"1985","journal-title":"Clin. Rheum. Dis."},{"key":"ref_19","first-page":"22","article-title":"Detection and clinical significance of IgE rheumatoid factor","volume":"11","author":"Mizushima","year":"1984","journal-title":"J. Rheumatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1136\/ard.43.2.246","article-title":"IgE class immune complexes in Felty\u2019s syndrome: Characterisation of antibody activities in isolated complexes","volume":"43","author":"Falus","year":"1984","journal-title":"Ann. Rheum. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1136\/ard.46.5.380","article-title":"Relation between bone erosions and rheumatoid factor isotypes","volume":"46","author":"Arnason","year":"1987","journal-title":"Ann. Rheum. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/BF02274780","article-title":"Significance of rheumatoid factor isotypes in seronegative rheumatoid arthritis","volume":"10","author":"Eggelmeijer","year":"1990","journal-title":"Rheumatol. Int."},{"key":"ref_23","first-page":"2119","article-title":"Clinical significance of IgA rheumatoid factor subclasses in rheumatoid arthritis","volume":"24","author":"Houssien","year":"1997","journal-title":"J. Rheumatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3109\/03009748809096769","article-title":"IgA rheumatoid factor as predictor of disease activity","volume":"75","author":"Teitsson","year":"1988","journal-title":"Scand. J. Rheumatol. Suppl."},{"key":"ref_25","first-page":"238","article-title":"IgA and IgM rheumatoid factors as markers of later erosive changes in rheumatoid arthritis (RA)","volume":"75","author":"Thompson","year":"1988","journal-title":"Scand. J. Rheumatol. Suppl."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1007\/s10067-006-0343-x","article-title":"Effects of rheumatoid factor isotypes on disease activity and severity in patients with rheumatoid arthritis: A comparative study","volume":"26","author":"Kinikli","year":"2007","journal-title":"Clin. Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"797","DOI":"10.7326\/0003-4819-146-11-200706050-00008","article-title":"Meta-analysis: Diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis","volume":"146","author":"Nishimura","year":"2007","journal-title":"Ann. Intern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wu, C.Y., Yang, H.Y., Luo, S.F., and Lai, J.H. (2021). From Rheumatoid Factor to Anti-Citrullinated Protein Antibodies and Anti-Carbamylated Protein Antibodies for Diagnosis and Prognosis Prediction in Patients with Rheumatoid Arthritis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020686"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e002817","DOI":"10.1136\/rmdopen-2022-002817","article-title":"Rheumatoid factor isotypes in rheumatoid arthritis diagnosis and prognosis: A systematic review and meta-analysis","volume":"9","author":"Motta","year":"2023","journal-title":"RMD Open"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.3899\/jrheum.091236","article-title":"Relationship between rheumatoid factor isotypes and IgG anti-cyclic citrullinated peptide antibodies","volume":"37","author":"Jaskowski","year":"2010","journal-title":"J. Rheumatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1093\/rheumatology\/32.7.546","article-title":"The relation between class-specific serum rheumatoid factors and age in the general population","volume":"32","author":"Lagaay","year":"1993","journal-title":"Br. J. Rheumatol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Dillon, C.F., Weisman, M.H., and Miller, F.W. (2020). Population-based estimates of humoral autoimmunity from the U.S. National Health and Nutrition Examination Surveys, 1960\u20132014. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0226516"},{"key":"ref_33","first-page":"2034","article-title":"Rheumatoid factors: What do they tell us?","volume":"29","author":"Newkirk","year":"2002","journal-title":"J. Rheumatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/j.amjmed.2013.09.002","article-title":"Racial and ethnic disparities in disease activity in patients with rheumatoid arthritis","volume":"126","author":"Greenberg","year":"2013","journal-title":"Am. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"663","DOI":"10.3899\/jrheum.211020","article-title":"Presence of Autoantibodies in Males and Females with Rheumatoid Arthritis: A Systematic Review and Metaanalysis","volume":"49","author":"Hadwen","year":"2022","journal-title":"J. Rheumatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1155\/2013\/726598","article-title":"Rheumatoid factors: Clinical applications","volume":"35","author":"Ingegnoli","year":"2013","journal-title":"Dis. Markers."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1136\/annrheumdis-2019-215463","article-title":"Shared epitope defines distinct associations of cigarette smoking with levels of anticitrullinated protein antibody and rheumatoid factor","volume":"78","author":"Ishikawa","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1084\/jem.148.5.1429","article-title":"In vitro effects of Epstein-Barr virus on peripheral blood mononuclear cells from patients with rheumatoid arthritis and normal subjects","volume":"148","author":"Slaughter","year":"1978","journal-title":"J. Exp. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/eji.1830080412","article-title":"Enhancement by IgM rheumatoid factor of in vitro ingestion by macrophages and in vivo clearance of aggregated IgG or antigen-antibody complexes","volume":"8","author":"Markowetz","year":"1978","journal-title":"Eur. J. Immunol."},{"key":"ref_40","first-page":"299","article-title":"Increased frequency of rheumatoid factor precursor B lymphocytes after immunization of normal adults with tetanus toxoid","volume":"51","author":"Welch","year":"1983","journal-title":"Clin. Exp. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1002\/art.40539","article-title":"Molecular Profiling and Clonal Tracking of Secreted Rheumatoid Factors in Primary Sj\u00f6gren\u2019s Syndrome","volume":"70","author":"Wang","year":"2018","journal-title":"Arthritis Rheumatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1136\/ard-2023-223901","article-title":"Rheumatoid factor autoantibody repertoire profiling reveals distinct binding epitopes in health and autoimmunity","volume":"82","author":"Oskam","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e004172","DOI":"10.1136\/rmdopen-2024-004172","article-title":"Next-generation rheumatoid factor assay provides improved predictive power for the development of arthritis in patients at risk","volume":"10","author":"Oskam","year":"2024","journal-title":"RMD Open"},{"key":"ref_44","first-page":"8","article-title":"Citrulline is an Essential Constituent of Antigenic Determinants Recognized by Rheumatoid Arthritis-specific Autoantibodies. 1998","volume":"195","author":"Schellekens","year":"2015","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1002\/art.20018","article-title":"Specific autoantibodies precede the symptoms of rheumatoid arthritis: A study of serial measurements in blood donors","volume":"50","author":"Nielen","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1002\/art.24827","article-title":"Anti-citrullinated peptide antibody assays and their role in the diagnosis of rheumatoid arthritis","volume":"61","author":"Aggarwal","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"103421","DOI":"10.1016\/j.autrev.2023.103421","article-title":"Should ACR\/EULAR criteria be revised changing the RF and ACPA scores?","volume":"23","author":"Steiner","year":"2024","journal-title":"Autoimmun. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3114","DOI":"10.1038\/s41467-024-47337-x","article-title":"Antigen-specific Fab profiling achieves molecular-resolution analysis of human autoantibody repertoires in rheumatoid arthritis","volume":"15","author":"Stork","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/s41584-024-01124-6","article-title":"The peculiar features, diversity and impact of citrulline-reactive autoantibodies","volume":"20","author":"Raposo","year":"2024","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13075-017-1266-4","article-title":"Poor prognostic factors guiding treatment decisions in rheumatoid arthritis patients: A review of data from randomized clinical trials and cohort studies","volume":"19","author":"Albrecht","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1136\/annrheumdis-2012-201517","article-title":"Rheumatoid factor determines structural progression of rheumatoid arthritis dependent and independent of disease activity","volume":"72","author":"Aletaha","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1136\/ard-2022-223356","article-title":"EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update","volume":"82","author":"Smolen","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1093\/rheumatology\/keae435","article-title":"Impact of high rheumatoid factor levels on treatment outcomes with certolizumab pegol and adalimumab in patients with rheumatoid arthritis","volume":"63","author":"Smolen","year":"2024","journal-title":"Rheumatology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.jbspin.2014.01.009","article-title":"Cardiovascular risk in rheumatoid arthritis","volume":"81","author":"Soubrier","year":"2014","journal-title":"Jt. Bone Spine"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1093\/rheumatology\/kep155","article-title":"A pilot risk model for the prediction of rapid radiographic progression in rheumatoid arthritis","volume":"48","author":"Vastesaeger","year":"2009","journal-title":"Rheumatology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e230144","DOI":"10.57264\/cer-2023-0144","article-title":"Real-world clinical outcomes and rationale for initiating abatacept as a first-line biologic for patients with anticitrullinated protein antibody- and rheumatoid factor-positive rheumatoid arthritis","volume":"13","author":"Balanean","year":"2024","journal-title":"J. Comp. Eff. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e000870","DOI":"10.1136\/rmdopen-2018-000870","article-title":"Window of opportunity in rheumatoid arthritis\u2014Definitions and supporting evidence: From old to new perspectives","volume":"5","author":"Burgers","year":"2019","journal-title":"RMD Open"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1002\/art.41752","article-title":"2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis","volume":"73","author":"Fraenkel","year":"2021","journal-title":"Arthritis Rheumatol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Milchram, L., Fischer, A., Huber, J., Soldo, R., Sieghart, D., Vierlinger, K., Bl\u00fcml, S., Steiner, G., and Weinh\u00e4usel, A. (2022). Functional Analysis of Autoantibody Signatures in Rheumatoid Arthritis. Molecules, 27.","DOI":"10.3390\/molecules27041452"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1136\/ard-2023-224728","article-title":"In early rheumatoid arthritis, anticitrullinated peptide antibodies associate with low number of affected joints and rheumatoid factor associates with systemic inflammation","volume":"83","author":"Pertsinidou","year":"2024","journal-title":"Ann. Rheum. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Guaracha-Bas\u00e1\u00f1ez, G.A., Contreras-Y\u00e1\u00f1ez, I., Ortiz-Haro, A.B., and Pascual-Ramos, V. (2024). Differences in referral path, clinical and radiographic outcomes between seronegative and seropositive rheumatoid arthritis Mexican Mestizo patients: A cohort study. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0304953"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/03009742.2018.1466362","article-title":"Anti-cyclic citrullinated peptide antibodies, 28-joint Disease Activity Score, and magnetic resonance imaging bone oedema at baseline predict 11 years\u2019 functional and radiographic outcome in early rheumatoid arthritis","volume":"48","author":"Hetland","year":"2019","journal-title":"Scand. J. Rheumatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"661","DOI":"10.21037\/atm-22-2171","article-title":"Seronegative rheumatic arthritis has milder inflammation and bone erosion in an ultrasound study of disease-modifying anti-rheumatic drugs (DMARDs)-na\u00efve Chinese cohort","volume":"10","author":"Lin","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.1002\/art.39306","article-title":"Rheumatoid Factor Is Associated with the Distribution of Hand Joint Destruction in Rheumatoid Arthritis","volume":"67","author":"Terao","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1136\/annrheumdis-2011-200379","article-title":"The association of treatment response and joint damage with ACPA-status in recent-onset RA: A subanalysis of the 8-year follow-up of the BeSt study","volume":"71","author":"Dirven","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/s13075-019-1909-8","article-title":"Outcome of patients with early arthritis without rheumatoid factor and ACPA and predictors of rheumatoid arthritis in the ESPOIR cohort","volume":"21","author":"Mouterde","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1136\/annrheumdis-2015-208873","article-title":"Patients with seronegative RA have more inflammatory activity compared with patients with seropositive RA in an inception cohort of DMARD-na\u00efve patients classified according to the 2010 ACR\/EULAR criteria","volume":"76","author":"Nordberg","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3897","DOI":"10.1007\/s00296-011-2329-5","article-title":"A comparative study on the diversity of clinical features between the sero-negative and sero-positive rheumatoid arthritis patients","volume":"32","author":"Geng","year":"2012","journal-title":"Rheumatol. Int."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3109\/03009749609080006","article-title":"Technetium-99m labelled human immunoglobulin scintigraphy predicts rheumatoid arthritis in patients with arthralgia","volume":"25","author":"Arndt","year":"1996","journal-title":"Scand. J. Rheumatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e5244","DOI":"10.1136\/bmj.e5244","article-title":"Elevated rheumatoid factor and long term risk of rheumatoid arthritis: A prospective cohort study","volume":"345","author":"Nielsen","year":"2012","journal-title":"BMJ"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.rdc.2010.02.001","article-title":"Preclinical rheumatoid arthritis: Identification, evaluation, and future directions for investigation","volume":"36","author":"Deane","year":"2010","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"R13","DOI":"10.1186\/ar3237","article-title":"Antibodies of IgG, IgA and IgM isotypes against cyclic citrullinated peptide precede the development of rheumatoid arthritis","volume":"13","author":"Kokkonen","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e000057","DOI":"10.1136\/rmdopen-2015-000057","article-title":"Rheumatoid arthritis treatment: The earlier the better to prevent joint damage","volume":"1","author":"Monti","year":"2015","journal-title":"RMD Open"},{"key":"ref_74","first-page":"170","article-title":"Biomarkers predicting a need for intensive treatment in patients with early arthritis","volume":"21","author":"Ortiz","year":"2015","journal-title":"Curr. Pharm. Des."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1136\/annrheumdis-2012-203130","article-title":"What is the evidence for the presence of a therapeutic window of opportunity in rheumatoid arthritis? A systematic literature review","volume":"73","author":"Krabben","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1186\/s13075-015-0707-1","article-title":"Sustained biologic-free and drug-free remission in rheumatoid arthritis, where are we now?","volume":"17","author":"Nagy","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1136\/annrheumdis-2014-206047","article-title":"Evaluating relationships between symptom duration and persistence of rheumatoid arthritis: Does a window of opportunity exist? Results on the Leiden early arthritis clinic and ESPOIR cohorts","volume":"74","author":"Tsonaka","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_78","first-page":"286","article-title":"Extra-articular Manifestations in Rheumatoid Arthritis","volume":"5","author":"Cojocaru","year":"2010","journal-title":"Maedica"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"102735","DOI":"10.1016\/j.autrev.2020.102735","article-title":"Beyond the joints, the extra-articular manifestations in rheumatoid arthritis","volume":"20","author":"Conforti","year":"2021","journal-title":"Autoimmun. Rev."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Radu, A.F., and Bungau, S.G. (2021). Management of Rheumatoid Arthritis: An Overview. Cells, 10.","DOI":"10.3390\/cells10112857"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"26","DOI":"10.17305\/bjbms.2010.2729","article-title":"Extra-articular manifestations of seronegative and seropositive rheumatoid arthritis","volume":"10","author":"Rexhepi","year":"2010","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"102776","DOI":"10.1016\/j.autrev.2021.102776","article-title":"Rheumatoid arthritis: Extra-articular manifestations and comorbidities","volume":"20","author":"Figus","year":"2021","journal-title":"Autoimmun. Rev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e014661","DOI":"10.1161\/JAHA.119.014661","article-title":"Heart Failure Risk Associated with Rheumatoid Arthritis-Related Chronic Inflammation","volume":"9","author":"Ahlers","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1016\/j.ijcard.2012.05.057","article-title":"Heart involvement in rheumatoid arthritis: Systematic review and meta-analysis","volume":"167","author":"Corrao","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_85","first-page":"416","article-title":"Cardiac magnetic resonance imaging reveals frequent myocardial involvement and dysfunction in active rheumatoid arthritis","volume":"34","author":"Koivuniemi","year":"2016","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3745","DOI":"10.1002\/ehf2.12947","article-title":"Incidence of congestive heart failure in rheumatoid arthritis: A review of literature and meta-regression analysis","volume":"7","author":"Khalid","year":"2020","journal-title":"ESC Heart Fail."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejrad.2018.01.005","article-title":"Influence of image reconstruction parameters on cardiovascular risk reclassification by Computed Tomography Coronary Artery Calcium Score","volume":"101","author":"Mantini","year":"2018","journal-title":"Eur. J. Radiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1136\/annrheumdis-2020-217653","article-title":"Cardiovascular effects of biological versus conventional synthetic disease-modifying antirheumatic drug therapy in treatment-na\u00efve, early rheumatoid arthritis","volume":"79","author":"Plein","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_89","first-page":"1368","article-title":"Myocardial T1 mapping by cardiac magnetic resonance imaging shows early myocardial changes in treatment-naive patients with active rheumatoid arthritis and positive autoantibodies","volume":"42","author":"Federico","year":"2024","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.3899\/jrheum.090188","article-title":"Autoantibodies and the risk of cardiovascular events","volume":"36","author":"Liang","year":"2009","journal-title":"J. Rheumatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s42358-019-0100-x","article-title":"Disease activity is associated with LV dysfunction in rheumatoid arthritis patients without clinical cardiovascular disease","volume":"59","author":"Hanvivadhanakul","year":"2019","journal-title":"Adv. Rheumatol."},{"key":"ref_92","first-page":"79","article-title":"Left ventricular function in treatment-naive early rheumatoid arthritis","volume":"4","author":"Deibjerg","year":"2014","journal-title":"Am. J. Cardiovasc. Dis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1111\/1756-185X.13992","article-title":"Disease severity affects myocardial functions in patients with treatment-naive early rheumatoid arthritis","volume":"24","author":"Tezcan","year":"2021","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1007\/s00296-023-05313-6","article-title":"Four-factor risk score for the prediction of interstitial lung disease in rheumatoid arthritis","volume":"43","author":"Koduri","year":"2023","journal-title":"Rheumatol. Int."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.clim.2018.05.004","article-title":"Combination of anti-citrullinated protein antibodies and rheumatoid factor is associated with increased systemic inflammatory mediators and more rapid progression from preclinical to clinical rheumatoid arthritis","volume":"195","author":"Lingampalli","year":"2018","journal-title":"Clin. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1513\/AnnalsATS.202006-590OC","article-title":"Autoantibody Seropositivity and Risk for Interstitial Lung Disease in a Prospective Male-Predominant Rheumatoid Arthritis Cohort of U.S. Veterans","volume":"18","author":"Natalini","year":"2021","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"4533","DOI":"10.1007\/s10067-021-05808-2","article-title":"Serum anti-citrullinated protein antibodies and rheumatoid factor increase the risk of rheumatoid arthritis-related interstitial lung disease: A meta-analysis","volume":"40","author":"Xie","year":"2021","journal-title":"Clin. Rheumatol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Xue, J., Hu, W., Wu, S., Wang, J., Chi, S., and Liu, X. (2022). Development of a Risk Nomogram Model for Identifying Interstitial Lung Disease in Patients with Rheumatoid Arthritis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.823669"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Zhang, M., Yin, J., and Zhang, X. (2023). Factors associated with interstitial lung disease in patients with rheumatoid arthritis: A systematic review and meta-analysis. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0286191"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1136\/annrheumdis-2015-208579","article-title":"Anticitrullinated protein antibodies and rheumatoid factor are associated with increased mortality but with different causes of death in patients with rheumatoid arthritis: A longitudinal study in three European cohorts","volume":"75","author":"Ajeganova","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Tyker, A., Ventura, I.B., Lee, C.T., Strykowski, R., Garcia, N., Guzy, R., Jablonski, R., Vij, R., Strek, M.E., and Chung, J.H. (2021). High-titer rheumatoid factor seropositivity predicts mediastinal lymphadenopathy and mortality in rheumatoid arthritis-related interstitial lung disease. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-02066-9"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Fragoulis, G.E., Nikiphorou, E., Larsen, J., Korsten, P., and Conway, R. (2019). Methotrexate-Associated Pneumonitis and Rheumatoid Arthritis-Interstitial Lung Disease: Current Concepts for the Diagnosis and Treatment. Front. Med., 6.","DOI":"10.3389\/fmed.2019.00238"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e233640","DOI":"10.1001\/jamanetworkopen.2023.3640","article-title":"Incidence of Interstitial Lung Disease in Patients with Rheumatoid Arthritis Treated with Biologic and Targeted Synthetic Disease-Modifying Antirheumatic Drugs","volume":"6","author":"Baker","year":"2023","journal-title":"JAMA Network Open"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Bendstrup, E., M\u00f8ller, J., Kronborg-White, S., Prior, T.S., and Hyldgaard, C. (2019). Interstitial Lung Disease in Rheumatoid Arthritis Remains a Challenge for Clinicians. J. Clin. Med., 8.","DOI":"10.3390\/jcm8122038"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e028466","DOI":"10.1136\/bmjopen-2018-028466","article-title":"Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohorts","volume":"9","author":"Kiely","year":"2019","journal-title":"BMJ Open"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1093\/rheumatology\/kez337","article-title":"Methotrexate and interstitial lung disease: Controversies and questions. A narrative review of the literature","volume":"58","author":"Fragoulis","year":"2019","journal-title":"Rheumatology"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1007\/s00296-020-04773-4","article-title":"Does methotrexate cause progressive fibrotic interstitial lung disease? A systematic review","volume":"41","author":"Dawson","year":"2021","journal-title":"Rheumatol. Int."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e000473","DOI":"10.1136\/rmdopen-2017-000473","article-title":"Mortality in patients with interstitial lung disease treated with rituximab or TNFi as a first biologic","volume":"3","author":"Druce","year":"2017","journal-title":"RMD Open"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1093\/rheumatology\/kex072","article-title":"Effect of rituximab on the progression of rheumatoid arthritis-related interstitial lung disease: 10 years\u2019 experience at a single centre","volume":"56","author":"Kabia","year":"2017","journal-title":"Rheumatology"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Cassone, G., Manfredi, A., Atzeni, F., Venerito, V., Vacchi, C., Picerno, V., Furini, F., Erre, G.L., Tomietto, P., and Fedele, A.L. (2020). Safety of Abatacept in Italian Patients with Rheumatoid Arthritis and Interstitial Lung Disease: A Multicenter Retrospective Study. J. Clin. Med., 9.","DOI":"10.3390\/jcm9010277"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.semarthrit.2017.12.012","article-title":"Abatacept in patients with rheumatoid arthritis and interstitial lung disease: A national multicenter study of 63 patients","volume":"48","author":"Loricera","year":"2018","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s10067-020-05227-9","article-title":"Non-anti-TNF biologic agents are associated with slower worsening of interstitial lung disease secondary to rheumatoid arthritis","volume":"40","author":"Espildora","year":"2021","journal-title":"Clin. Rheumatol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1111\/imj.14670","article-title":"Tocilizumab therapy in rheumatoid arthritis with interstitial lung disease: A multicentre retrospective study","volume":"50","author":"Manfredi","year":"2020","journal-title":"Intern. Med. J."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"103636","DOI":"10.1016\/j.autrev.2024.103636","article-title":"Janus kinase inhibitors in rheumatoid arthritis-associated interstitial lung disease: A systematic review and meta-analysis","volume":"23","author":"Nolla","year":"2024","journal-title":"Autoimmun. Rev."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.reuma.2011.12.008","article-title":"Interstitial lung disease related to rheumatoid arthritis: Evolution after treatment","volume":"8","author":"Carrillo","year":"2012","journal-title":"Reumatol. Clin."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1007\/s10067-023-06623-7","article-title":"Effect of nintedanib in patients with progressive pulmonary fibrosis associated with rheumatoid arthritis: Data from the INBUILD trial","volume":"42","author":"Matteson","year":"2023","journal-title":"Clin. Rheumatol."},{"key":"ref_117","first-page":"62","article-title":"Occurrence of extraarticular disease manifestations is associated with excess mortality in a community based cohort of patients with rheumatoid arthritis","volume":"29","author":"Turesson","year":"2002","journal-title":"J. Rheumatol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1093\/rheumatology\/ket475","article-title":"Vasculitis associated with rheumatoid arthritis: A case-control study","volume":"53","author":"Makol","year":"2014","journal-title":"Rheumatology"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1097\/BOR.0b013e32831c5303","article-title":"Vasculitis in rheumatoid arthritis","volume":"21","author":"Turesson","year":"2009","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1136\/ard.62.8.722","article-title":"Extra-articular disease manifestations in rheumatoid arthritis: Incidence trends and risk factors over 46 years","volume":"62","author":"Turesson","year":"2003","journal-title":"Ann. Rheum. Dis."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1136\/ard.55.3.190","article-title":"Factors associated with the development of vasculitis in rheumatoid arthritis: Results of a case-control study","volume":"55","author":"Voskuyl","year":"1996","journal-title":"Ann. Rheum. Dis."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1097\/00005792-198611000-00002","article-title":"Rheumatoid vasculitis: Survival and associated risk factors","volume":"65","author":"Vollertsen","year":"1986","journal-title":"Medicine (Baltimore)"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1136\/ard.46.10.727","article-title":"Clinical and serological features of severe vasculitis in rheumatoid arthritis: Prognostic implications","volume":"46","author":"Geirsson","year":"1987","journal-title":"Ann. Rheum. Dis."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.semarthrit.2006.04.006","article-title":"Systemic rheumatoid vasculitis: A review","volume":"36","author":"Genta","year":"2006","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1136\/annrheumdis-2020-217344","article-title":"EULAR definition of difficult-to-treat rheumatoid arthritis","volume":"80","author":"Nagy","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"e002842","DOI":"10.1136\/rmdopen-2022-002842","article-title":"Difficult-to-treat rheumatoid arthritis (D2T RA): Clinical issues at early stages of disease","volume":"9","author":"Leon","year":"2023","journal-title":"RMD Open"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3778","DOI":"10.1093\/rheumatology\/keaa860","article-title":"Difficult-to-treat rheumatoid arthritis: Contributing factors and burden of disease","volume":"60","author":"Roodenrijs","year":"2021","journal-title":"Rheumatology"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1093\/rheumatology\/keae265","article-title":"Predictive factors and treatment outcomes associated with difficult-to-treat rheumatoid arthritis conditions: The ANSWER cohort study","volume":"63","author":"Watanabe","year":"2024","journal-title":"Rheumatology"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1080\/25785826.2021.1928383","article-title":"Prevalence and predictive factors of difficult-to-treat rheumatoid arthritis: The KURAMA cohort","volume":"45","author":"Watanabe","year":"2022","journal-title":"Immunol. Med."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Watanabe, R., Okano, T., Gon, T., Yoshida, N., Fukumoto, K., Yamada, S., and Hashimoto, M. (2022). Difficult-to-treat rheumatoid arthritis: Current concept and unsolved problems. Front. Med., 9.","DOI":"10.3389\/fmed.2022.1049875"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1093\/rheumatology\/keae544","article-title":"Difficult-to-treat rheumatoid arthritis: What have we learned and what do we still need to learn?","volume":"64","author":"Hofman","year":"2025","journal-title":"Rheumatology"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1136\/annrheumdis-2022-222370","article-title":"Interferon-\u03b1-mediated therapeutic resistance in early rheumatoid arthritis implicates epigenetic reprogramming","volume":"81","author":"Cooles","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Iwasaki, T., Watanabe, R., Ito, H., Fujii, T., Okuma, K., Oku, T., Hirayama, Y., Ohmura, K., Murata, K., and Murakami, K. (2022). Dynamics of Type I and Type II Interferon Signature Determines Responsiveness to Anti-TNF Therapy in Rheumatoid Arthritis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.901437"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/art.1780310302","article-title":"The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis","volume":"31","author":"Arnett","year":"1988","journal-title":"Arthritis Rheum."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1136\/ard.2010.148759","article-title":"Highest clinical effectiveness of rituximab in autoantibody-positive patients with rheumatoid arthritis and in those for whom no more than one previous TNF antagonist has failed: Pooled data from 10 European registries","volume":"70","author":"Chatzidionysiou","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1136\/ard.2007.084715","article-title":"Association of rheumatoid factor and anti-cyclic citrullinated peptide positivity, but not carriage of shared epitope or PTPN22 susceptibility variants, with anti-tumour necrosis factor response in rheumatoid arthritis","volume":"68","author":"Potter","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1136\/ard.2004.023523","article-title":"Rheumatoid factor, but not anti-cyclic citrullinated peptide antibodies, is modulated by infliximab treatment in rheumatoid arthritis","volume":"64","author":"Verhelst","year":"2005","journal-title":"Ann. Rheum. Dis."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13075-015-0553-1","article-title":"Haptoglobin-\u03b11, -\u03b12, vitamin D-binding protein and apolipoprotein C-III as predictors of etanercept drug response in rheumatoid arthritis","volume":"17","author":"Blaschke","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1136\/ard.2006.060608","article-title":"High IgA rheumatoid factor levels are associated with poor clinical response to tumour necrosis factor alpha inhibitors in rheumatoid arthritis","volume":"66","author":"Caporali","year":"2007","journal-title":"Ann. Rheum. Dis."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"163","DOI":"10.46497\/ArchRheumatol.2020.7499","article-title":"Factors Predicting Early Failure of Etanercept in Rheumatoid Arthritis: An Analysis from the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis) Registry","volume":"35","author":"Sebastiani","year":"2020","journal-title":"Arch. Rheumatol."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Zhao, Z., Hua, Z., Luo, X., Li, Y., Yu, L., Li, M., Lu, C., Zhao, T., and Liu, Y. (2022). Application and pharmacological mechanism of methotrexate in rheumatoid arthritis. Biomed. Pharmacother., 150.","DOI":"10.1016\/j.biopha.2022.113074"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1136\/ard.2008.088237","article-title":"Can clinical factors at presentation be used to predict outcome of treatment with methotrexate in patients with early inflammatory polyarthritis?","volume":"68","author":"Hider","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1136\/ard.2010.139212","article-title":"Predictors of response to methotrexate in early DMARD naive rheumatoid arthritis: Results from the initial open-label phase of the SWEFOT trial","volume":"70","author":"Saevarsdottir","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1093\/rheumatology\/key263","article-title":"Autoantibody status is not associated with early treatment response to first-line methotrexate in patients with early rheumatoid arthritis","volume":"58","author":"Dekkers","year":"2019","journal-title":"Rheumatology"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13075-018-1544-9","article-title":"Risk factors for oral methotrexate failure in patients with inflammatory polyarthritis: Results from a UK prospective cohort study","volume":"20","author":"Bluett","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1002\/art.40810","article-title":"Profiling of Gene Expression Biomarkers as a Classifier of Methotrexate Nonresponse in Patients with Rheumatoid Arthritis","volume":"71","author":"Plant","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1136\/ard.2006.063412","article-title":"Rheumatoid arthritis subtypes identified by genomic profiling of peripheral blood cells: Assignment of a type I interferon signature in a subpopulation of patients","volume":"66","author":"Wijbrandts","year":"2007","journal-title":"Ann. Rheum. Dis."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1093\/rheumatology\/39.6.655","article-title":"A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis","volume":"39","author":"Emery","year":"2000","journal-title":"Rheumatology"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1093\/rheumatology\/ker356","article-title":"Effectiveness of sulfasalazine and methotrexate in 1102 DMARD-naive patients with early RA","volume":"51","author":"Lie","year":"2012","journal-title":"Rheumatology"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"i1777","DOI":"10.1136\/bmj.i1777","article-title":"Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: Abridged Cochrane systematic review and network meta-analysis","volume":"353","author":"Hazlewood","year":"2016","journal-title":"BMJ"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/nrrheum.2015.171","article-title":"Cytokines in rheumatoid arthritis\u2014Shaping the immunological landscape","volume":"12","author":"McInnes","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1093\/rheumatology\/keq325","article-title":"Long-term effectiveness and safety of TNF-blocking agents in daily clinical practice: Results from the Dutch Rheumatoid Arthritis Monitoring register","volume":"50","author":"Kievit","year":"2011","journal-title":"Rheumatology"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13075-020-2122-5","article-title":"Insensitivity versus poor response to tumour necrosis factor inhibitors in rheumatoid arthritis: A retrospective cohort study","volume":"22","author":"Ochi","year":"2020","journal-title":"Arthritis Res. Ther."},{"key":"ref_154","first-page":"1670","article-title":"Good clinical response, remission, and predictors of remission in rheumatoid arthritis patients treated with tumor necrosis factor-alpha blockers: The GISEA study","volume":"34","author":"Mancarella","year":"2007","journal-title":"J. Rheumatol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"e14181","DOI":"10.1097\/MD.0000000000014181","article-title":"Rheumatoid factor as predictor of response to treatment with anti-TNF alpha drugs in patients with rheumatoid arthritis: Results of a cohort study","volume":"98","author":"Castro","year":"2019","journal-title":"Medicine"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1080\/03009742.2019.1602670","article-title":"Association of female sex and positive rheumatoid factor with low serum infliximab and anti-drug antibodies, related to treatment failure in early rheumatoid arthritis: Results from the SWEFOT trial population","volume":"48","author":"Hambardzumyan","year":"2019","journal-title":"Scand. J. Rheumatol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1007\/s00296-021-05086-w","article-title":"Differential efficacy of TNF inhibitors with or without the immunoglobulin fragment crystallizable (Fc) portion in rheumatoid arthritis: The ANSWER cohort study","volume":"42","author":"Nakayama","year":"2022","journal-title":"Rheumatol. Int."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1111\/1756-185X.14699","article-title":"Efficacy of certolizumab pegol across baseline rheumatoid factor subgroups in patients with rheumatoid arthritis: Post-hoc analysis of clinical trials","volume":"26","author":"Tanaka","year":"2023","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_159","first-page":"999","article-title":"Influence of rheumatoid factor on serum drug levels of TNF inhibitors with different structures in rheumatoid arthritis","volume":"42","author":"Gehin","year":"2024","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"e003975","DOI":"10.1136\/rmdopen-2023-003975","article-title":"Exploring the influence of baseline rheumatoid factor levels on TNF inhibitor retention rate in patients with rheumatoid arthritis: A multicentre and retrospective study","volume":"10","author":"Cepas","year":"2024","journal-title":"RMD Open"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"102392","DOI":"10.1016\/j.jaut.2019.102392","article-title":"An overview of autoantibodies in rheumatoid arthritis","volume":"110","author":"Huizinga","year":"2020","journal-title":"J. Autoimmun."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/nri856","article-title":"Roles of Fc receptors in autoimmunity","volume":"2","author":"Takai","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Junker, F., Gordon, J., and Qureshi, O. (2020). Fc Gamma Receptors and Their Role in Antigen Uptake, Presentation, and T Cell Activation. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01393"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1093\/rheumatology\/keq285","article-title":"Certolizumab pegol in the treatment of rheumatoid arthritis: A comprehensive review of its clinical efficacy and safety","volume":"50","author":"Mease","year":"2011","journal-title":"Rheumatology"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.tips.2018.07.007","article-title":"Targeting FcRn to Generate Antibody-Based Therapeutics","volume":"39","author":"Ward","year":"2018","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/nri2155","article-title":"FcRn: The neonatal Fc receptor comes of age","volume":"7","author":"Roopenian","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Oyama, S., Ebina, K., Etani, Y., Hirao, M., Kyuuma, M., Fujii, Y., Iwata, K., Ogawa, B., Hasegawa, T., and Kawano, S. (2022). A novel anti-TNF-\u03b1 drug ozoralizumab rapidly distributes to inflamed joint tissues in a mouse model of collagen induced arthritis. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-23152-6"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1002\/art.42273","article-title":"Phase II\/III Results of a Trial of Anti-Tumor Necrosis Factor Multivalent NANOBODY Compound Ozoralizumab in Patients with Rheumatoid Arthritis","volume":"74","author":"Takeuchi","year":"2022","journal-title":"Arthritis Rheumatol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1759720X221114101","DOI":"10.1177\/1759720X221114101","article-title":"Managing inadequate response to initial anti-TNF therapy in rheumatoid arthritis: Optimising treatment outcomes","volume":"14","author":"Taylor","year":"2022","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"102398","DOI":"10.1016\/j.autrev.2019.102398","article-title":"Failure of anti-TNF treatment in patients with rheumatoid arthritis: The pros and cons of the early use of alternative biological agents","volume":"18","author":"Kedves","year":"2019","journal-title":"Autoimmun. Rev."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Shams, S., Martinez, J.M., Dawson, J.R.D., Flores, J., Gabriel, M., Garcia, G., Guevara, A., Murray, K., Pacifici, N., and Vargas, M.V. (2021). The Therapeutic Landscape of Rheumatoid Arthritis: Current State and Future Directions. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.680043"},{"key":"ref_172","first-page":"1882","article-title":"Analysis of efficacy and safety of abatacept for rheumatoid arthritis: Systematic review and meta-analysis","volume":"41","author":"Wu","year":"2023","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"113819","DOI":"10.1016\/j.celrep.2024.113819","article-title":"Structural insights into IL-6 signaling inhibition by therapeutic antibodies","volume":"43","author":"Wang","year":"2024","journal-title":"Cell Rep."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1007\/s10067-019-04699-8","article-title":"A comprehensive review of rituximab therapy in rheumatoid arthritis patients","volume":"38","author":"Tavakolpour","year":"2019","journal-title":"Clin. Rheumatol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s13075-021-02547-2","article-title":"Serum TNF\u03b1 levels at 24 h after certolizumab pegol predict effectiveness at week 12 in patients with rheumatoid arthritis from TSUBAME study","volume":"23","author":"Miyazaki","year":"2021","journal-title":"Arthritis Res. Ther."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.semarthrit.2012.11.007","article-title":"Rheumatoid factor as predictor of response to abatacept, rituximab and tocilizumab in rheumatoid arthritis: Systematic review and meta-analysis","volume":"43","author":"Maneiro","year":"2013","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"370","DOI":"10.3109\/s10165-010-0409-0","article-title":"In rheumatoid arthritis patients treated with tocilizumab, the rate of clinical disease activity index (CDAI) remission at 24 weeks is superior in those with higher titers of IgM-rheumatoid factor at baseline","volume":"21","author":"Kawashiri","year":"2011","journal-title":"Mod. Rheumatol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1136\/ard.2010.139725","article-title":"Effectiveness and safety of the interleukin 6-receptor antagonist tocilizumab after 4 and 24 weeks in patients with active rheumatoid arthritis: The first phase IIIb real-life study (TAMARA)","volume":"70","author":"Burmester","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"kex062.230","DOI":"10.1093\/rheumatology\/kex062.230","article-title":"229. Clinical responses of sarilumab based on rheumatoid factor and anti-cyclic citrullinated peptide antibody status in patients with rheumatoid arthritis","volume":"56","author":"Emery","year":"2017","journal-title":"Rheumatology"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1136\/annrheumdis-2011-201109","article-title":"Positivity for anti-cyclic citrullinated peptide is associated with a better response to abatacept: Data from the \u2018Orencia and Rheumatoid Arthritis\u2019 registry","volume":"71","author":"Gottenberg","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1002\/art.39595","article-title":"Brief Report: Association of Rheumatoid Factor and Anti-Citrullinated Protein Antibody Positivity with Better Effectiveness of Abatacept: Results from the Pan-European Registry Analysis","volume":"68","author":"Gottenberg","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1007\/s10067-019-04449-w","article-title":"Predictors of abatacept retention over 2 years in patients with rheumatoid arthritis: Results from the real-world ACTION study","volume":"38","author":"Alten","year":"2019","journal-title":"Clin. Rheumatol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13075-018-1527-x","article-title":"Abatacept blocks anti-citrullinated protein antibody and rheumatoid factor mediated cytokine production in human macrophages in IDO-dependent manner","volume":"20","author":"Bozec","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1136\/ard-2024-226024","article-title":"Association of rheumatoid factor, anti-citrullinated protein antibodies and shared epitope with clinical response to initial treatment in patients with early rheumatoid arthritis: Data from a randomised controlled trial","volume":"83","author":"Lend","year":"2024","journal-title":"Ann. Rheum. Dis."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1620\/tjem.250.153","article-title":"Better Retention of Abatacept Is Associated with High Rheumatoid Factor: A Five-Year Follow-Up Study of Patients with Rheumatoid Arthritis","volume":"250","author":"Okazaki","year":"2020","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Martinez-Molina, C., Gich, I., Diaz-Torn\u00e9, C., Park, H.S., Feliu, A., Vidal, S., and Corominas, H. (2024). Patient-related factors influencing the effectiveness and safety of Janus Kinase inhibitors in rheumatoid arthritis: A real-world study. Sci. Rep., 14.","DOI":"10.1038\/s41598-023-50379-8"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"e000742","DOI":"10.1136\/rmdopen-2018-000742","article-title":"Treatment outcomes in patients with seropositive versus seronegative rheumatoid arthritis in Phase III randomised clinical trials of tofacitinib","volume":"5","author":"Bird","year":"2019","journal-title":"RMD Open"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/acr2.1010","article-title":"Persistence of Tofacitinib in the Treatment of Rheumatoid Arthritis in Open-Label, Long-Term Extension Studies up to 9.5 Years","volume":"1","author":"Pope","year":"2019","journal-title":"ACR Open Rheumatol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/5\/1529\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:41:53Z","timestamp":1760028113000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/5\/1529"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,25]]},"references-count":188,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["jcm14051529"],"URL":"https:\/\/doi.org\/10.3390\/jcm14051529","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,25]]}}}