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BIOlogical Factors that Limit sustAined Remission in rhEumatoid arthritis (the BIO-FLARE study): protocol for a non-randomised longitudinal cohort study.
Rayner, Fiona; Anderson, Amy E; Baker, Kenneth F; Buckley, Christopher D; Dyke, Bernard; Fenton, Sally; Filer, Andrew; Goodyear, Carl S; Hilkens, Catharien M U; Hiu, Shaun; Kerrigan, Sean; Kurowska-Stolarska, Mariola; Matthews, Fiona; McInnes, Iain; Ng, Wan-Fai; Pratt, Arthur G; Prichard, Jonathan; Raza, Karim; Siebert, Stefan; Stocken, Deborah; Teare, M Dawn; Young, Stephen; Isaacs, John D.
  • Rayner F; Translational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. Fiona.rayner1@newcastle.ac.uk.
  • Anderson AE; Musculoskeletal Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. Fiona.rayner1@newcastle.ac.uk.
  • Baker KF; Translational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
  • Buckley CD; Translational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
  • Dyke B; Musculoskeletal Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • Fenton S; NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and Institute for Inflammation and Ageing, University of Birmingham, Birmingham, UK.
  • Filer A; NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and Institute for Inflammation and Ageing, University of Birmingham, Birmingham, UK.
  • Goodyear CS; NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and Institute for Inflammation and Ageing, University of Birmingham, Birmingham, UK.
  • Hilkens CMU; NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and Institute for Inflammation and Ageing, University of Birmingham, Birmingham, UK.
  • Hiu S; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
  • Kerrigan S; Translational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
  • Kurowska-Stolarska M; Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
  • Matthews F; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
  • McInnes I; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
  • Ng WF; Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
  • Pratt AG; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
  • Prichard J; Translational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
  • Raza K; Musculoskeletal Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • Siebert S; Translational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
  • Stocken D; Musculoskeletal Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • Teare MD; Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
  • Young S; NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and Institute for Inflammation and Ageing, University of Birmingham, Birmingham, UK.
  • Isaacs JD; Department of Rheumatology, Sandwell and West Birmingham NHS Trust, Birmingham, UK.
BMC Rheumatol ; 5(1): 22, 2021 Jul 19.
Article in English | MEDLINE | ID: covidwho-1388846
ABSTRACT

BACKGROUND:

Our 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.

METHODS:

The 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 REGISTRATION The study was retrospectively registered on 27/06/2019 in the ISRCTN registry 16371380 .
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Cohort study / Etiology study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Language: English Journal: BMC Rheumatol Year: 2021 Document Type: Article Affiliation country: S41927-021-00194-3

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Cohort study / Etiology study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Language: English Journal: BMC Rheumatol Year: 2021 Document Type: Article Affiliation country: S41927-021-00194-3