{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T14:09:13Z","timestamp":1791727753512,"version":"4.3.4"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study investigated the clinical outcomes of stepwise dose-reduction and discontinuation protocols for biological disease-modifying anti-rheumatic drugs (bDMARD) in patients with stable rheumatoid arthritis (RA), and explored predictors of disease flares.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Seventy-one patients in clinical remission for \u2265\u20096 months were enrolled in the Reduction group. In Phase 1, dosing intervals were extended to 1.5 and then 2.0 times the standard schedule for patients who maintained low disease activity (LDA) for \u2265\u200912 months. Patients who sustained LDA (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200941) advanced to Phase 2 for complete bDMARD discontinuation. Seventy-one matched patients who continued standard therapy served as controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In Phase 1, 12-month flare-free population rates were 80.6% in the Reduction group and 87.1% in the control group. Adverse events leading to discontinuation were rare in both groups. Gray-scale ultrasound findings were associated with flares during dose reduction (Wald \u03c7\u00b2=2.3,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04, OR 1.06). In Phase 2, 47.5% of patients experienced flares after bDMARD discontinuation, and the 24-month flare-free population rate was significantly lower in the Reduction group (52.5%) compared to controls (86.6%) (HR 4.6, 95% CI: 2.2\u201311.0,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Serious adverse events were infrequent and occurred only in the control group. Power Doppler scores and ACPA-positivity were predictive of flares, while concomitant methotrexate use reduced flare risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Tapering bDMARD may maintain disease control short-term, but discontinuation increases flare risk. Ultrasound findings and ACPA-positivity are valuable predictors, and concomitant methotrexate use may help prevent flares after discontinuation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13075-025-03672-y","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T11:23:55Z","timestamp":1762255435000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Stepwise dose reduction and discontinuation of bDMARD in rheumatoid arthritis: a prospective cohort study of flare-free population, flares, and predictive markers"],"prefix":"10.1186","volume":"27","author":[{"given":"Yuji","family":"Nozaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Kishimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Tomita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsu","family":"Itami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisato","family":"Ashida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Shiga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Yamazawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Ishimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Morimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rika","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Kinoshita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"3672_CR1","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1001\/jama.2018.13103","volume":"320","author":"D Aletaha","year":"2018","unstructured":"Aletaha D, Smolen JS. 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