Evidence map›Paper›PMID 40204305›Full record

ArticleBMJ open2025

Clinical predictors of flare and drug-free remission in rheumatoid arthritis: preliminary results from the prospective BIO-FLARE experimental medicine study.

Fiona Rayner, Shaun Hiu, Andrew Melville, Theophile Bigirumurame, Amy Anderson, Bernard Dyke, Sean Kerrigan, Andrew McGucken, Jonathan Prichard, Mohadeseh Shojaei Shahrokhabadi and 12 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in BMJ open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Fiona RaynerTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0003-4302-0899
Shaun Hiu *Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0003-1699-4348
Andrew Melville *Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Theophile BigirumuramePopulation Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0003-2387-4918
Amy AndersonTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Bernard DykeInstitute of Inflammation and Ageing, NIHR Birmingham Biomedical Research Centre, Birmingham, UK.
Sean KerriganInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Andrew McGuckenInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Jonathan PrichardPopulation Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Mohadeseh Shojaei ShahrokhabadiPopulation Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Catharien M U HilkensTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Christopher D BuckleyInstitute of Inflammation and Ageing, NIHR Birmingham Biomedical Research Centre, Birmingham, UK.
Iain B McInnesInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Wan-Fai NgTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Carl GoodyearInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Dawn TearePopulation Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Andrew FilerInstitute of Inflammation and Ageing, NIHR Birmingham Biomedical Research Centre, Birmingham, UK.
Stefan SiebertInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.ORCID http://orcid.org/0000-0002-1802-7311
Karim RazaInstitute of Inflammation and Ageing, NIHR Birmingham Biomedical Research Centre, Birmingham, UK.
Arthur PrattTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Kenneth F BakerTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
John IsaacsTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK john.isaacs@ncl.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesHuge advances in rheumatoid arthritis (RA) treatment mean an increasing number of patients now achieve disease remission. However, long-term treatments can carry side effects and associated financial costs. In addition, some patients still experience painful and debilitating disease flares, the mechanisms of which are poorly understood. High rates of flare and a lack of effective prediction tools can limit attempts at treatment withdrawal. The BIOlogical Factors that Limit sustAined Remission in rhEumatoid arthritis (BIO-FLARE) experimental medicine study was designed to study flare and remission immunobiology. Here, we present the clinical outcomes and predictors of drug-free remission and flare, and develop a prediction model to estimate flare risk. DESIGN, SETTING AND

participantsBIO-FLARE was a multicentre, prospective, single-arm, open-label experimental medicine study conducted across seven National Health Service Trusts in the UK. Participants had established RA in clinical remission (disease activity score in 28 joints with C reactive protein (DAS28-CRP)<2.4) and were receiving methotrexate, sulfasalazine or hydroxychloroquine (monotherapy or combination).

interventionsThe intervention was disease-modifying anti-rheumatic drug cessation, followed by observation for 24 weeks or until flare, with clinical and immune monitoring. OUTCOME MEASURES: The primary outcome measure was the proportion of participants experiencing a confirmed flare, defined as DAS28-CRP≥3.2 or DAS28-CRP≥2.4 twice within 2 weeks, and time to flare. Exploratory predictive modelling was also performed using multivariable Cox regression to understand risk factors for flare.

results121 participants were recruited between September 2018 and December 2020. Flare rate by week 24 was 52.3% (95% CI 43.0 to 61.7), with a median (IQR) time to flare of 63 (41-96) days. Female sex, baseline methotrexate use, anti-citrullinated peptide antibody level and rheumatoid factor level were associated with flare. An exploratory prediction model incorporating these variables allowed estimation of flare risk, with acceptable classification (C index 0.709) and good calibration performance.

conclusionThe rate of flare was approximately 50%. Several baseline clinical parameters were associated with flare. The BIO-FLARE study design provides a robust experimental medicine model for studying flare and remission immunobiology. TRIAL REGISTRATION NUMBER: ISRCTN registry 16371380.

Indexed as

Antirheumatic AgentsArthritis, RheumatoidAdultAgedDrug Therapy, CombinationFemaleHumansHydroxychloroquineMaleMethotrexateMiddle AgedProspective StudiesRemission InductionSeverity of Illness IndexSulfasalazineSymptom Flare UpAntirheumatic AgentsHydroxychloroquineMethotrexateSulfasalazineDrug TherapyIMMUNOLOGYRheumatology

Identifiers

PMID40204305
PMCPMC11987156

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.