{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T20:42:31Z","timestamp":1793479351639,"version":"4.5.0"},"reference-count":47,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"unspecified","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","award":["GR-2009-1608032"],"award-info":[{"award-number":["GR-2009-1608032"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007365","name":"Fondazione IRCCS Policlinico San Matteo","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007365","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,1,1]]},"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To delineate, within the framework of current clinical practice and criteria, the sustainability of first-line immuno-suppressive treatment discontinuation in rheumatoid arthritis (RA) and the impact of residual disease in remission on long-term drug-free (DF) outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>RA patients, referring to the Pavia early arthritis clinic (EAC) between 2009 and 2021 and achieving remission after Disease Activity Score-driven methotrexate (MTX) monotherapy, were recruited. Eligible patients underwent DF follow-up at 3-month intervals over 5 years after MTX discontinuation. Pre-selected clinical, serological and ultrasound (US) exposure variables at MTX withdrawal were analysed using multivariable Cox regression to predict time-to-flare.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 761 EAC patients with RA, 132 started DF follow-up (person-months: 3678). 62 experienced a flare after a median (range) of 9 (3\u201360) months, resulting in a progressive decline in flare-free survival throughout the observation period. Whole-cohort multivariate Cox regression identified anti-citrullinated protein antibody (ACPA) positivity (HR: 4.20, 95%\u2009CI 2.37 to 7.44) and hands\u2019 joints with grey scale (US-GS) alterations (GS&gt;1; HR: 2.18, 95%\u2009CI 1.20 to 3.93) as independent predictors. ACPA-positive patients in Simplified Disease Activity Index (SDAI) remission displayed a flare-free survival estimate at 5 years of 6.4% (95% CI 1.2 to 35.7) versus 78.2% (95% CI 67.4 to 90.8) for ACPA-negative patients in SDAI remission without residual US-GS alteration in hands\u2019 joints (n=59); the latter group showing no evidence of radiographic progression and functional deterioration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Long-term DF remission is attainable in a niche subset of ACPA-negative RA. Examining clinical and subclinical residual synovial abnormalities during remission allows for effective preemptive identification of this subset in real life.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2024-005079","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T08:40:54Z","timestamp":1738140054000},"page":"e005079","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Prediction of long-term drug-free outcomes in ACPA-positive and ACPA-negative rheumatoid arthritis by combined clinical and ultrasound assessment of residual disease: a 5-year prospective study"],"prefix":"10.1136","volume":"11","author":[{"given":"Antonio","family":"Manzo","sequence":"first","affiliation":[{"name":"Rheumatology and Translational Immunology Research Laboratories (LaRIT), Department of Internal Medicine and Therapeutics, Universita di Pavia, Pavia, Italy"},{"name":"Arthritis Research Clinic (ARC), Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6578-6938","authenticated-orcid":false,"given":"Emanuele","family":"Bozzalla Cassione","sequence":"additional","affiliation":[{"name":"Rheumatology and Translational Immunology Research Laboratories (LaRIT), Department of Internal Medicine and Therapeutics, Universita di Pavia, Pavia, Italy"},{"name":"Arthritis Research Clinic (ARC), Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlomaurizio","family":"Montecucco","sequence":"additional","affiliation":[{"name":"Rheumatology and Translational Immunology Research Laboratories (LaRIT), Department of Internal Medicine and Therapeutics, Universita di Pavia, Pavia, Italy"},{"name":"Arthritis Research Clinic (ARC), Division of Rheumatology, 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terenzj","family":"Luvaro","sequence":"additional","affiliation":[{"name":"Rheumatology and Translational Immunology Research Laboratories (LaRIT), Department of Internal Medicine and Therapeutics, Universita di Pavia, Pavia, Italy"},{"name":"Arthritis Research Clinic (ARC), Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ylenia","family":"Sammali","sequence":"additional","affiliation":[{"name":"Rheumatology and Translational Immunology Research Laboratories (LaRIT), Department of Internal Medicine and Therapeutics, Universita di Pavia, Pavia, Italy"},{"name":"Arthritis Research Clinic (ARC), Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2312-2161","authenticated-orcid":false,"given":"Ludovico","family":"De Stefano","sequence":"additional","affiliation":[{"name":"Rheumatology and Translational Immunology Research Laboratories (LaRIT), Department of Internal Medicine and Therapeutics, Universita di Pavia, Pavia, Italy"},{"name":"Arthritis Research Clinic (ARC), Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Alpini","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemical-Clinical Analyses, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Klersy","sequence":"additional","affiliation":[{"name":"Biostatistics and Clinical Trial Center, Fondazione IRCCS Policlinico San Matteo, Pavia, 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