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However, data on long-term outcomes in ACPA-positive individuals without RA are limited. This study aimed to investigate the 6-year cumulative incidence of RA and radiographic progression among ACPA-positive individuals without RA at baseline in a population-based cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>A total of 1541 participants without RA at baseline were enrolled from the population-based cohort, of whom 28 tested positive for ACPA. Incident cases of RA were identified based on participants\u2019 self-reported physician diagnosis and medication history over a 6-year follow-up period. Radiographic progression in the hands was assessed using the van der Heijde modified Sharp score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Five participants developed RA within the first 3 years, including three who were ACPA-positive at baseline (all with high ACPA titres). After 3\u00a0years, additional RA cases were identified only among participants who were ACPA-negative at baseline, whereas no further cases occurred among those who were ACPA-positive at baseline. The positive predictive value of ACPA for RA within 3 years was 15.0%, rising to 30.0% among those with high ACPA titres. When it was combined with the rheumatoid factor or matrix metalloproteinase-3, the positive predictive value further increased. Radiographic progression occurred in all participants with high-titre ACPA who developed RA (n\u2009=\u20093) and in one ACPA-positive individual without RA, but not in ACPA-negative individuals who developed RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ACPA positivity, particularly at high titres, may be associated with an increased risk of incident RA and with radiographic bone destruction, even in the absence of clinical symptoms or an RA diagnosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/mr\/roag051","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T11:42:42Z","timestamp":1781955762000},"page":"918-926","source":"Crossref","is-referenced-by-count":0,"title":["Incidence and radiographic progression of rheumatoid arthritis in anti-citrullinated protein antibody-positive individuals: A 6-year population-based cohort study"],"prefix":"10.1093","volume":"36","author":[{"given":"Kenta","family":"Makabe","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2363-9803","authenticated-orcid":false,"given":"Takumi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo , Tokyo ,","place":["Japan"]},{"name":"Department of Orthopaedics, Jichi Medical University , Tochigi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Uchio","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyasu","family":"Mizuhara","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryutaro","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiko","family":"Iidaka","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine for Locomotive Organ Disorders, 22nd Century Medical and Research Center, The University of Tokyo , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Kasai","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Omata","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9210-9414","authenticated-orcid":false,"given":"Sakae","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine for Locomotive Organ Disorders, 22nd Century Medical and Research Center, The University of Tokyo , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"2026110407424913300_ref1","doi-asserted-by":"crossref","first-page":"e070856","DOI":"10.1136\/bmj-2022-070856","article-title":"Therapeutic advances in rheumatoid arthritis","volume":"384","author":"Brown","year":"2024","journal-title":"BMJ"},{"key":"2026110407424913300_ref2","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":"2026110407424913300_ref3","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/nrrheum.2015.8","article-title":"Rheumatoid arthritis therapy reappraisal: strategies, opportunities and challenges","volume":"11","author":"Smolen","year":"2015","journal-title":"Nat Rev Rheumatol"},{"key":"2026110407424913300_ref4","doi-asserted-by":"crossref","first-page":"e000870","DOI":"10.1136\/rmdopen-2018-000870","article-title":"Window of opportunity in rheumatoid arthritis - 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