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

Rayner, F. et al. (2021) BIOlogical Factors that Limit sustAined Remission in rhEumatoid arthritis (the BIO-FLARE study): protocol for a non-randomised longitudinal cohort study. BMC Rheumatology, 5, 22. (doi: 10.1186/s41927-021-00194-3) (PMID:34275488) (PMCID:PMC8286860)

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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.

Item Type:Articles
Additional Information:Funding: The study is funded by an experimental medicine challenge grant from the Medical Research Council, grant code: MR/N026977/1. The study was peerreviewed as part of the grant application process. KFB is funded by a National Institute for Health Research (NIHR) Clinical Lectureship (CL-2017-01- 004).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Kurowska-Stolarska, Dr Mariola and Kerrigan, Dr Sean and Siebert, Professor Stefan and Goodyear, Professor Carl
Authors: Rayner, F., Anderson, A. E., Baker, K. F., Buckley, C. D., Dyke, B., Fenton, S., Filer, A., Goodyear, C. S., Hilkens, C. M. U., Hiu, S., Kerrigan, S., Kurowska-Stolarska, M., Matthews, F., McInnes, I., Ng, W.-F., Pratt, A. G., Prichard, J., Raza, K., Siebert, S., Stocken, D., Teare, M. D., Young, S., and Isaacs, J. D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:BMC Rheumatology
Publisher:BMC
ISSN:2520-1026
Published Online:19 July 2021
Copyright Holders:Copyright © The Author(s) 2021
First Published:First published in BMC Rheumatology 5:22
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
174136BIOlogical Factors that Limit sustAined Remission in rhEumatoid arthritis (BIO-FLARE study)Iain McInnesMedical Research Council (MRC)MR/N026977/1III - Immunology