Patient-reported outcomes as early warning signs of flare following drug cessation in rheumatoid arthritis
Objectives 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 syntheti...
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BMJ Publishing Group
2025-04-01
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| Online Access: | https://rmdopen.bmj.com/content/11/2/e005442.full |
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| author | Iain B McInnes Stefan Siebert Andrew Filer Karim Raza Wan-Fai Ng Christopher D Buckley John D Isaacs Andrew Melville Andrew McGucken Amy E Anderson Bernard Dyke Arthur G Pratt Kenneth F Baker Leher Gumber Najib Naamane Theophile Bigirumurame James MS Wason Fiona Rayner Sean Kerrigan Jonathan Prichard |
| author_facet | Iain B McInnes Stefan Siebert Andrew Filer Karim Raza Wan-Fai Ng Christopher D Buckley John D Isaacs Andrew Melville Andrew McGucken Amy E Anderson Bernard Dyke Arthur G Pratt Kenneth F Baker Leher Gumber Najib Naamane Theophile Bigirumurame James MS Wason Fiona Rayner Sean Kerrigan Jonathan Prichard |
| author_sort | Iain B McInnes |
| collection | DOAJ |
| description | Objectives 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.Methods 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) ≥3.2 at any visit, (ii) DAS28-CRP≥2.4 on two visits within 2 weeks or (iii) resuming DMARD and/or steroid therapy despite DAS28-CRP<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.Results 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<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% CI 0.84 to 0.96; p=0.001); for example, an RA-FQ increment of ≥5.5 from baseline identified objective flare with positive and negative predictive values of 80% and 91%, respectively.Conclusions Our data support the potential value of remote PRO monitoring of RA patients in drug-free remission to identify flare occurrence. |
| format | Article |
| id | doaj-art-365fc716be5d4841a6d37bc0f516d8a7 |
| institution | OA Journals |
| issn | 2056-5933 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMJ Publishing Group |
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| series | RMD Open |
| spelling | doaj-art-365fc716be5d4841a6d37bc0f516d8a72025-08-20T01:55:41ZengBMJ Publishing GroupRMD Open2056-59332025-04-0111210.1136/rmdopen-2025-005442Patient-reported outcomes as early warning signs of flare following drug cessation in rheumatoid arthritisIain B McInnes0Stefan Siebert1Andrew Filer2Karim Raza3Wan-Fai Ng4Christopher D Buckley5John D Isaacs6Andrew Melville7Andrew McGucken8Amy E Anderson9Bernard Dyke10Arthur G Pratt11Kenneth F Baker12Leher Gumber13Najib Naamane14Theophile Bigirumurame15James MS Wason16Fiona Rayner17Sean Kerrigan18Jonathan Prichard19School of Infection and Immunity, University of Glasgow, Glasgow, UKSchool of Infection and Immunity, University of Glasgow, Glasgow, UKNIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UKNIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UKTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UKKennedy Institue for Rheumatology, University of Oxford, Oxford, UKTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UKSchool of Infection and Immunity, University of Glasgow, Glasgow, UKSchool of Infection and Immunity, University of Glasgow, Glasgow, UKTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UKNIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UKTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UKTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UKTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UKTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UKPopulation Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UKPopulation Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UKTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UKSchool of Infection and Immunity, University of Glasgow, Glasgow, UKNewcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UKObjectives 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.Methods 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) ≥3.2 at any visit, (ii) DAS28-CRP≥2.4 on two visits within 2 weeks or (iii) resuming DMARD and/or steroid therapy despite DAS28-CRP<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.Results 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<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% CI 0.84 to 0.96; p=0.001); for example, an RA-FQ increment of ≥5.5 from baseline identified objective flare with positive and negative predictive values of 80% and 91%, respectively.Conclusions Our data support the potential value of remote PRO monitoring of RA patients in drug-free remission to identify flare occurrence.https://rmdopen.bmj.com/content/11/2/e005442.full |
| spellingShingle | Iain B McInnes Stefan Siebert Andrew Filer Karim Raza Wan-Fai Ng Christopher D Buckley John D Isaacs Andrew Melville Andrew McGucken Amy E Anderson Bernard Dyke Arthur G Pratt Kenneth F Baker Leher Gumber Najib Naamane Theophile Bigirumurame James MS Wason Fiona Rayner Sean Kerrigan Jonathan Prichard Patient-reported outcomes as early warning signs of flare following drug cessation in rheumatoid arthritis RMD Open |
| title | Patient-reported outcomes as early warning signs of flare following drug cessation in rheumatoid arthritis |
| title_full | Patient-reported outcomes as early warning signs of flare following drug cessation in rheumatoid arthritis |
| title_fullStr | Patient-reported outcomes as early warning signs of flare following drug cessation in rheumatoid arthritis |
| title_full_unstemmed | Patient-reported outcomes as early warning signs of flare following drug cessation in rheumatoid arthritis |
| title_short | Patient-reported outcomes as early warning signs of flare following drug cessation in rheumatoid arthritis |
| title_sort | patient reported outcomes as early warning signs of flare following drug cessation in rheumatoid arthritis |
| url | https://rmdopen.bmj.com/content/11/2/e005442.full |
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