{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T17:24:55Z","timestamp":1763400295123,"version":"3.44.0"},"reference-count":28,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIHR Research Professorship","award":["NIHR301614 to JMSW"],"award-info":[{"award-number":["NIHR301614 to JMSW"]}]},{"name":"Medical Research Council Experimental Medicine Challenge Grant","award":["MR\/N026977\/1"],"award-info":[{"award-number":["MR\/N026977\/1"]}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute for Health and Care Research Advanced Fellowship","award":["NIHR303620 to KFB"],"award-info":[{"award-number":["NIHR303620 to KFB"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,3,18]]},"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Drug withdrawal in rheumatoid arthritis (RA) in remission can reduce toxicity, but with the risk of flare which requires close monitoring. We explored the potential of patient-reported outcomes (PROs) for flare detection among RA patients in sustained remission after conventional synthetic disease-modifying antirheumatic drug (csDMARD) cessation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Four PROs (Factors that Limit sustAined Remission in rhEumatoid arthritis (FLARE-RA), EuroQol-5 Dimensions (EQ5D), Routine Assessment of Patient Index Data-3 (RAPID-3) and RA Flare Questionnaire (RA-FQ)) were captured at baseline and at sequential visits until time-of-flare or end of 6-month follow-up as part of the BIO-FLARE prospective cohort study. Flare was defined as any of (i) Disease Activity Score 28 (DAS28)-C reactive protein (CRP) \u22653.2 at any visit, (ii) DAS28-CRP\u22652.4 on two visits within 2 weeks or (iii) resuming DMARD and\/or steroid therapy despite DAS28-CRP&lt;2.4. Cox regression models with time-varying covariates were fitted to evaluate associations between PRO changes and likelihood of flare. Receiver-operating characteristic (ROC) curves enabled discriminatory changes in each PRO to be compared as a means of identifying flare.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>58\/121 (47.9%) participants (70.1% females, mean age 64.8 years) experienced a flare. A 1-point change in each PRO score was strongly associated with flare development in the multivariate Cox regression model (p&lt;0.001 in each case). ROC curve analysis confirmed that monitoring adverse changes in PROs from baseline offered robust discriminatory utility for identifying flare occurrence. This was most evident for RA-FQ and FLARE-RA (both areas under the curves 0.90, 95%\u2009CI 0.84 to 0.96; p=0.001); for example, an RA-FQ increment of \u22655.5 from baseline identified objective flare with positive and negative predictive values of 80% and 91%, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our data support the potential value of remote PRO monitoring of RA patients in drug-free remission to identify flare occurrence.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2025-005442","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T17:17:47Z","timestamp":1743527867000},"page":"e005442","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Patient-reported outcomes as early warning signs of flare following drug cessation in rheumatoid arthritis"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0154-1207","authenticated-orcid":false,"given":"Leher","family":"Gumber","sequence":"first","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4302-0899","authenticated-orcid":false,"given":"Fiona","family":"Rayner","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK"},{"name":"Musculoskeletal Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theophile","family":"Bigirumurame","sequence":"additional","affiliation":[{"name":"Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Dyke","sequence":"additional","affiliation":[{"name":"NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Melville","sequence":"additional","affiliation":[{"name":"School of Infection and Immunity, University of Glasgow, Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean","family":"Kerrigan","sequence":"additional","affiliation":[{"name":"School of Infection and Immunity, University of Glasgow, Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"McGucken","sequence":"additional","affiliation":[{"name":"School of Infection and Immunity, University of Glasgow, Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Najib","family":"Naamane","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Prichard","sequence":"additional","affiliation":[{"name":"Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher D","family":"Buckley","sequence":"additional","affiliation":[{"name":"Kennedy Institue for Rheumatology, University of Oxford, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8164-6249","authenticated-orcid":false,"given":"Andrew","family":"Filer","sequence":"additional","affiliation":[{"name":"NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6462-4280","authenticated-orcid":false,"given":"Iain B","family":"McInnes","sequence":"additional","affiliation":[{"name":"School of Infection and Immunity, University of Glasgow, Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1570-1232","authenticated-orcid":false,"given":"Karim","family":"Raza","sequence":"additional","affiliation":[{"name":"NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK"},{"name":"Department of Rheumatology, Bronglais General Hospital, Aberystwyth, UK"},{"name":"Department of Rheumatology, Sandwell and West Birmingham NHS Trust, Birmingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1802-7311","authenticated-orcid":false,"given":"Stefan","family":"Siebert","sequence":"additional","affiliation":[{"name":"School of Infection and Immunity, University of Glasgow, Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James MS","family":"Wason","sequence":"additional","affiliation":[{"name":"Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan-Fai","family":"Ng","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK"},{"name":"University College Cork, Cork, Republic of Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy E","family":"Anderson","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John D","family":"Isaacs","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK"},{"name":"Musculoskeletal Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth F","family":"Baker","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK"},{"name":"Musculoskeletal Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur G","family":"Pratt","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK"},{"name":"Musculoskeletal Unit, 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