Evidence map›Paper›PMID 34275488›Full record

ArticleBMC rheumatology2021

BIOlogical Factors that Limit sustAined Remission in rhEumatoid arthritis (the BIO-FLARE study): protocol for a non-randomised longitudinal cohort study.

Fiona Rayner, Amy E Anderson, Kenneth F Baker, Christopher D Buckley, Bernard Dyke, Sally Fenton, Andrew Filer, Carl S Goodyear, Catharien M U Hilkens, Shaun Hiu and 13 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC rheumatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.2field-weighted citation impact, top 21% of its field
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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Observational
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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

23 authors at 4 institutions in 1 country.

Fiona RaynerTranslational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. Fiona.rayner1@newcastle.ac.uk.ORCID http://orcid.org/0000-0003-4302-0899
Amy E AndersonTranslational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Kenneth F BakerTranslational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Christopher D BuckleyNIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and Institute for Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Bernard DykeNIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and Institute for Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Sally FentonNIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and Institute for Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Andrew FilerNIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and Institute for Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Carl S GoodyearInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Catharien M U HilkensTranslational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Shaun HiuPopulation Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Sean KerriganInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Mariola Kurowska-StolarskaInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Fiona MatthewsPopulation Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Iain McInnesInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Wan-Fai NgTranslational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Arthur G PrattTranslational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Jonathan PrichardPopulation Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Karim RazaNIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and Institute for Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Stefan SiebertInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Deborah StockenPopulation Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
M Dawn TearePopulation Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Stephen YoungNIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and Institute for Inflammation and Ageing, University of Birmingham, Birmingham, UK.
John D IsaacsTranslational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Newcastle University · GBUniversity Hospitals Birmingham NHS Foundation Trust · GBNewcastle upon Tyne Hospitals NHS Foundation Trust · GBUniversity of Glasgow · GB

Funding

Medical Research Council MR/N026977/1Medical Research Council MR/P020941/1
6 · The paper itself

Abstract

backgroundOur knowledge of immune-mediated inflammatory disease (IMID) aetiology and pathogenesis has improved greatly over recent years, however, very little is known of the factors that trigger disease relapses (flares), converting diseases from inactive to active states. Focussing on rheumatoid arthritis (RA), the challenge that we will address is why IMIDs remit and relapse. Extrapolating from pathogenetic factors involved in disease initiation, new episodes of inflammation could be triggered by recurrent systemic immune dysregulation or locally by factors within the joint, either of which could be endorsed by overarching epigenetic factors or changes in systemic or localised metabolism.

methodsThe BIO-FLARE study is a non-randomised longitudinal cohort study that aims to enrol 150 patients with RA in remission on a stable dose of non-biologic disease-modifying anti-rheumatic drugs (DMARDs), who consent to discontinue treatment. Participants stop their DMARDs at time 0 and are offered an optional ultrasound-guided synovial biopsy. They are studied intensively, with blood sampling and clinical evaluation at weeks 0, 2, 5, 8, 12 and 24. It is anticipated that 50% of participants will have a disease flare, whilst 50% remain in drug-free remission for the study duration (24 weeks). Flaring participants undergo an ultrasound-guided synovial biopsy before reinstatement of previous treatment. Blood samples will be used to investigate immune cell subsets, their activation status and their cytokine profile, autoantibody profiles and epigenetic profiles. Synovial biopsies will be examined to profile cell lineages and subtypes present at flare. Blood, urine and synovium will be examined to determine metabolic profiles. Taking into account all generated data, multivariate statistical techniques will be employed to develop a model to predict impending flare in RA, highlighting therapeutic pathways and informative biomarkers. Despite initial recruitment to time and target, the SARS-CoV-2 pandemic has impacted significantly, and a decision was taken to close recruitment at 118 participants with complete data. DISCUSSION: This study aims to investigate the pathogenesis of flare in rheumatoid arthritis, which is a significant knowledge gap in our understanding, addressing a major unmet patient need.

trial registrationThe study was retrospectively registered on 27/06/2019 in the ISRCTN registry 16371380 .

Indexed as

DMARD cessationDMARD withdrawalFlarePathogenesisRemissionRheumatoid arthritis

Identifiers

PMID34275488
PMCPMC8286860
OpenAlexW3184354873

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.