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Patients with RA who maintained a simplified disease activity index\u2009\u2264\u20093.3 for\u2009\u2265\u20093\u00a0months during November 2014\u2013January 2018 in our medical centre in Tokyo, Japan, were eligible. The primary endpoint was flare (disease activity score 28\u2014erythrocyte sedimentation rate\u2009\u2265\u20093.2 with increase from baseline\u2009&gt;\u20090.6) within 2\u00a0years after bDMARD discontinuation. Comprehensive clinical assessments, ultrasonographic evaluation of 40 joints, and blood sampling for 12 biomarkers were performed every 2\u20133\u00a0months for 2\u00a0years unless patients experienced flare. Flare-positive and flare-negative patients were compared using univariate and Kaplan\u2013Meier analyses. Thirty-six patients (80.6% female, median disease duration, 5.2\u00a0years; median treatment period with discontinued bDMARD, 2\u00a0years; median remission duration, 18\u00a0months) were enrolled. Twenty patients (55.6%) experienced RA flare 43\u2013651 (median, 115) days after the first skipped date of bDMARDs. Two patients who withdrew without disease flare were excluded from the comparison. Clinical and ultrasonographic evaluations did not show significant between-group differences; Kaplan\u2013Meier analysis showed that higher baseline soluble tumour necrosis factor receptor 1 (sTNFR1) concentration impacted subsequent disease flare (p\u2009=\u20090.0041); higher baseline interleukin (IL)-2 concentration was exclusively beneficial to patients with lower sTNFR1 (p\u2009=\u20090.0058), resulting in remission maintenance in 83.3% of patients with lower sTNFR1 and higher IL-2. We demonstrated the usefulness of combined biomarker evaluation for predicting sustained remission after bDMARD discontinuation in RA.<\/jats:p>","DOI":"10.1038\/s41598-021-86335-7","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T11:06:58Z","timestamp":1616670418000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Prediction of disease flare by biomarkers after discontinuing biologics in patients with rheumatoid arthritis achieving stringent remission"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4330-5782","authenticated-orcid":false,"given":"Hideto","family":"Kameda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayako","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaharu","family":"Katagiri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuto","family":"Takakura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayaka","family":"Takenaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Ito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kennosuke","family":"Mizushina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takehisa","family":"Ogura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"key":"86335_CR1","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1136\/annrheumdis-2019-216655","volume":"79","author":"JS Smolen","year":"2020","unstructured":"Smolen, J. 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H.K. has received consulting fees, speaking fees, and\/or honoraria from AbbVie G.K., Asahi Kasei Pharma, Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Eli Lilly Japan K.K., Gilead Sciences, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma, Novartis Pharma K.K., and Sanofi Pharma; and has received research grants from AbbVie G.K., Asahi Kasei Pharma, Astellas Pharma Inc., Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma, Novartis Pharma K.K., and Sanofi Pharma. T.O. has received honoraria from AbbVie G.K. A.H., T.K., Y.T., Y.I., S.T., H.I. and K.M. declare no potential conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6865"}}