MICA: BIOlogical Factors that Limit sustAined Remission in rhEumatoid arthritis (the BIO-FLARE study)

Lead Research Organisation: Newcastle University
Department Name: Institute of Cellular Medicine

Abstract

Diseases such as rheumatoid arthritis (RA) relapse and remit. In other words, symptoms come and go unpredictably. This adds to the physical and psychological burden for patients because, even when they are well, they face the prospect of a sudden deterioration in their health. Imagine, for example, the impact of such an event when starting a new job or when about to go on a long-awaited vacation. Joint inflammation also causes joint damage which in turn causes disability, as well as contributing to conditions such as heart disease and stroke. So every flare has added potential consequences for longterm health.

Despite advances in understanding of the causes of RA, we understand almost nothing about what leads to disease 'flare' (an alternative term for relapse). There are a number of possibilities. RA is a so-called autoimmune disease in which the body's immune system turns inwards and starts to attack the joints and other tissues. So, when the disease is inactive the immune system may revert back to the normal state, only to become triggered again leading up to relapse. There are a number of different white blood cells that contribute to the immune system, several of which could be implicated in a flare. Although some white blood cells are damaging, others can regulate the immune response, and the balance between these two types of cell appears to be critical in diseases such as RA. Also, some of the 'bad' cells produce autoantibodies (proteins that can damage the tissues), and changes in these autoantibodies could trigger flares. Alternatively, we now understand that there are cells in the joint (synovial fibroblasts) that can influence the activity of the immune system, and which therefore could be important in determining when a flare happens. Just like the immune cells, fibroblasts themselves can also exist in 'good' and 'bad' forms. Lastly, all of the cells mentioned above can undergo 'epigenetic' modification. This is a process that influences the activity of the DNA in a cell and determines whether a particular gene is switched on or off. We believe that epigenetics is an important determinant of whether someone develops RA, and also of how severe their disease is. Similarly, epigenetic changes could influence whether or not a patient flares.

Because flares occur unpredictably they are difficult to study scientifically. However, we have developed a human 'model' which will allow us to study the underlying processes. As already implied, up to a third of patients with RA enter periods of remission, which can last for months or years. Many patients then ask whether they can stop their medicines and, if they do, about a half flare and the remainder remain well, for variable periods of time - although currently we cannot tell which patients will flare. We will ask patients with RA, in remission, whether they would like to stop their medicines. If they do, and they agree to take part in our research, we will assess them at intervals for 6 months after stopping treatment - initially fortnightly, then less frequently. Each time we see them we will take a blood sample for analysis in the laboratory. When they initially stop their medicines, and again if they flare, we will also ask to take a sample of the lining of their inflamed joint in a simple procedure which does not require admission to hospital.

We will use the samples we have collected to address the various possibilities for flare listed above. By comparing samples from patients who flare and those who don't we will be able to gain a better understanding of the pathways that trigger flare. In the longer term this should allow us to develop treatments that prevent or interrupt flare, as well as to predict the patients who are most likely to flare, in whom it is less safe to stop treatment. We believe that this could lead to new treatment approaches for such patients, enhancing their quality of life and long-term health.

Technical Summary

Flares of immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA), are a major burden for patients. They occur unpredictably, adding to the physical and psychological burden of the condition, and contribute to joint damage and comorbidities, such as cardiovascular disease. Flares are difficult to study, precisely because of their unpredictable timing. However, we have established a human model that generates a 'synchronized' population of RA patients in clinical remission, of whom about 50% flare within 6 months, the remainder maintaining remission. We propose to carefully study such a population to better understand the factors that determine disease flare.

Up to a third of patients with RA achieve disease remission with aggressive therapy. Many wish to discontinue therapy at this point and, if they do, about 50% flare in the subsequent 6 months. We will follow such a population prospectively, to study the biological processes underpinning flare. We will study 150 patients in clinical remission for at least 6 months, and prepared to discontinue treatment. After treatment cessation patients will be studied intensively, with blood sampling at weeks 2, 4, 6, 12 and 24. Patients will also undergo ultrasound-guided biopsy of 'flaring' synovium before reinstatement of previous treatment (with which patients readily regain remission). We will also obtain biopsies from consenting patients at baseline and in remission at 6 months.

In blood we will study immune cell subsets and their activation status; autoantibody profiles; and epigenetic profiles. Synovial biopsies will allow us to examine the cell lineages present, including stromal cell subtypes, as well as inflammatory mediators. We will additionally examine metabolic profiles in blood, urine and synoivum.

Using multivariate statistical techniques we will develop a model that predicts impending flare in RA, highlighting tractable therapeutic pathways and informative biomarkers.

Planned Impact

The successful conclusion of this work will have wide-ranging impacts. By unravelling the causes of flare in rheumatoid arthritis it will suggest novel pathways for intervention, to prevent flare as well as improving our ability to predict flare. In turn this will enable the targeted withdrawal of therapy from patients in remission - to avoid flares in the 50% (approx) of patients who continue to need these drugs. Furthermore, this research is likely to have implications for the immune-mediated inflammatory diseases in general. These include psoriasis, psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease (Crohn disease, ulcerative colitis) and the connective tissue diseases (systemic lupus erythematosus, systemic sclerosis, Sjogren's syndrome, polymyositis, systemic vasculitis). All of these diseases remit and relapse and the underlying mechanisms are likely to be related. Thus, the beneficiaries of this research will include:

PATIENTS with the above diseases - flare is an enormous burden to patients. Not only do they have to live with a life-long inflammatory condition but the unpredictable nature of these diseases significantly hampers planning, both in relation to work and leisure time. For example the impact of a flare at the start of a new job or preceding a long-awaited vacation is massive. Flares also lead to incremental organ damage and increase susceptibility to comorbidities such as cardiovascular disease. Therefore an ability to predict and prevent flare and, indeed, to stop drugs in patients who do not need them, would greatly improve quality of life for patients.

SCIENTISTS working on these diseases. The identification of flare pathways will catalyse new work programmes in these and related areas, both in ACADEMIA and in INDUSTRY. In particular the ability to target these pathways in an informed way could lead to the development of medicines to prevent or disrupt flare - ie medicines that could be taken prophylactically or immediately a patient senses an impending flare. The coupling of these drugs to predictive biomarkers should enable flares to be both predicted and prevented in a stratified manner. This could therefore develop into a new branch of 'preventative' medicine, with benefits to both academia and industry.

The HEALTH AND WEALTH of the nation. The ability to prevent flares, or to intervene early, will improve the health of the nation whilst also maintaining productivity by keeping patients in work. It will also provide new therapeutic targets and pathways, and companion diagnostics, for our partners in Industry. Furthermore, the ability to discontinue drugs in patients who don't require them will result in tangible savings in direct healthcare costs.

POLICY MAKERS. Quality Standards have hugely improved the outlook for patients with early arthritis (and other inflammatory diseases). However, if a patient achieves remission then they move out of medical focus until they flare again. This can feed their insecurity and reduces their quality of life, even during 'good' spells. In contrast, understanding the science of flare should lead to new policies aimed specifically at this patient group. For example, the intermittent measurement of biomarkers informed by the proposed work will enable the prediction and curtailment of flares, as indicated above, and this should result in new guidelines and policies for this stage of the disease.

The MRC have invested heavily in immune mediated inflammatory diseases, and the proposed work would link in with the outcomes of several of these ongoing projects, such as RA-MAP, MATURA and PSORT, many of which are linked with national and international industrial partners. The successful conclusion and integration of these projects will send a strong signal from the UK in terms of our capabilities in the Life Sciences, attracting inward investment and enhancing the global economic performance and competitiveness of the United Kingdom.

Publications

10 25 50
 
Description A: Arthritis Research UK Disease Subcommittee Meeting, Chesterfield, 2018
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
URL https://www.versusarthritis.org/research/research-funding-and-policy/our-charitable-subcommittees/
 
Description A: NIHR ARUK Musculoskeletal Experimental Medicine Conference 2018, Nottingham 2018
Geographic Reach National 
Policy Influence Type Participation in a national consultation
URL https://www.arthritisresearchuk.org/research/news-for-researchers/2018/july/maximising-msk-experimen...
 
Description Arthritis Research UK Strategic Workshop - Stacking the Odds Towards a Cure - Versus Arthritis London 2018
Geographic Reach National 
Policy Influence Type Participation in a national consultation
 
Description Chair - EULAR STUDY GROUP ON THERAPEUTIC DRUG MONITORING OF BIOLOGICS
Geographic Reach Europe 
Policy Influence Type Membership of a guideline committee
URL https://www.eular.org/myUploadData/files/publication_document_therapeutic_drug_monitoring_study_grou...
 
Description EULAR 2019 Planning Committee, Amsterdam, 2018
Geographic Reach Europe 
Policy Influence Type Membership of a guideline committee
 
Description MRC Translational Research Group London 2018
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
URL https://mrc.ukri.org/about/our-structure/strategy-board-overview-groups/translational-research-group...
 
Description MRC Translational Research Group, London, 2019
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
URL https://mrc.ukri.org/about/our-structure/strategy-board-overview-groups/translational-research-group...
 
Description NICE Assessment Sub-Group Meeting for the Diagnostics Assessment Programme, Manchester 2018
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
URL https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/nice-diagnostics-guidance
 
Description NIHR BRC Impact Showcase, Newcastle, 2018
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact Influential meeting on Healthy Ageing as a research priority of national importance, as exemplified by our NIHR BRC.
URL https://www.newcastlebrc.nihr.ac.uk/nihr-newcastle-biomedical-research-centre-impact-showcase-presen...
 
Description RT-CURE Regulatory meeting with MHRA, representing RT-CURE regulatory subgroup
Geographic Reach Europe 
Policy Influence Type Participation in a national consultation
URL https://www.rtcure.com/
 
Description TRC Steering Committee, London, 2018 with VA and NOCRI
Geographic Reach National 
Policy Influence Type Participation in a national consultation
 
Description Wellcome Trust 4WARD Meeting 2016 - Clinical PhD Funding - Newcastle, Leeds, Manchester, Sheffield
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
Impact Consortium Clinical PhD Funding Meeting
URL http://www.4wardnorth.org.uk/
 
Description BIOFLARE - Biological factors that limit sustained remission in Rheumatoid Arthritis
Amount £2,825,228 (GBP)
Funding ID MR/N026977/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 04/2017 
End 03/2019
 
Description CeMaRRA: Cellular markers of relapse in rheumatoid arthritis.
Amount £37,800 (GBP)
Organisation British Society for Rheumatology (BSR) 
Sector Learned Society
Country United Kingdom
Start 09/2018 
End 09/2019
 
Description EU IMI2 (Rheuma Tolerance for Cure [RTCure]) - Newcastle
Amount € 6,000,000 (EUR)
Funding ID 777357 
Organisation European Commission 
Department Innovative Medicines Initiative (IMI)
Sector Multiple
Country European Union (EU)
Start 06/2017 
End 05/2022
 
Description Investigation into serum interferon-a as a prognostic marker of clinical response in early RA
Amount £15,143 (GBP)
Organisation British Society for Rheumatology (BSR) 
Sector Learned Society
Country United Kingdom
Start 09/2018 
End 08/2019
 
Description NIHR Newcastle Biomedical Research Centre in Ageing and Long-term conditions
Amount £17,460,811 (GBP)
Organisation National Institute for Health Research 
Department NIHR Biomedical Research Centre
Sector Academic/University
Country United Kingdom
Start 04/2017 
End 03/2022
 
Description A: RA Centre of Excellence - Birmingham Scientific Meeting. 
Organisation University of Birmingham
Department Birmingham Clinical Trials Unit
Country Unknown 
Sector Academic/University 
PI Contribution Workshop on fibroblasts by Lilian Nwosu. Presentations my myself on TRAFIC and BioFlare studies.
Collaborator Contribution Equal partners with Glasgow and Birmingham.
Impact See additional awards and publications stemming from the RACE centre.
Start Year 2015
 
Description A: RA Centre of Excellence - Birmingham Scientific Meeting. 
Organisation University of Glasgow
Department Mental Health Rights Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution Workshop on fibroblasts by Lilian Nwosu. Presentations my myself on TRAFIC and BioFlare studies.
Collaborator Contribution Equal partners with Glasgow and Birmingham.
Impact See additional awards and publications stemming from the RACE centre.
Start Year 2015
 
Description A: RT-CURE consortium 
Organisation Karolinska Institute
Department Department of Medical Biochemistry and Biophysics
Country Sweden 
Sector Academic/University 
PI Contribution First annual meeting hosted by Janssen. Presented on the achievements of Work Package 6 including regulatory guidance on tolerance trials and steps to secure regulatory buy-in.
Collaborator Contribution Feedback and discussions around prospective trials.
Impact Knowledge sharing package in development.
Start Year 2018
 
Description ARUK Centre of Excellence in rheumatoid arthritis pathogenesis 
Organisation University of Birmingham
Country United Kingdom 
Sector Academic/University 
PI Contribution WE have written a successful funding application to Arthritis Research UK for a Centre of Excellence in RA pathogenesis, value £2.5m over five years
Collaborator Contribution Each centre will provide a unique scientific contribution to the Centre
Impact Research grant, valu £2.5m spread across the three centres. Renewed 2019 with addition of KIR, Oxford University
Start Year 2013
 
Description ARUK Centre of Excellence in rheumatoid arthritis pathogenesis 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution WE have written a successful funding application to Arthritis Research UK for a Centre of Excellence in RA pathogenesis, value £2.5m over five years
Collaborator Contribution Each centre will provide a unique scientific contribution to the Centre
Impact Research grant, valu £2.5m spread across the three centres. Renewed 2019 with addition of KIR, Oxford University
Start Year 2013
 
Description ARUK Centre of Excellence in rheumatoid arthritis pathogenesis 
Organisation University of Oxford
Department Kennedy Institute of Rheumatology
Country United Kingdom 
Sector Academic/University 
PI Contribution WE have written a successful funding application to Arthritis Research UK for a Centre of Excellence in RA pathogenesis, value £2.5m over five years
Collaborator Contribution Each centre will provide a unique scientific contribution to the Centre
Impact Research grant, valu £2.5m spread across the three centres. Renewed 2019 with addition of KIR, Oxford University
Start Year 2013
 
Description ARUK-NIHR Newcastle Experimental Arthritis Treatment Centre 2016 
Organisation Versus Arthritis
PI Contribution Clinical, imaging, statistical and bioinformatics support.
Collaborator Contribution Infrastructure support including laboratory technical support, research nurses, project management, biostatistical and database management support. This has been crucial in tendering for other awards and trials.
Impact See Publications
Start Year 2012
 
Description Annual Clinical Academic Training Pathway Scientific Meeting, Newcastle 2018 
Organisation National Institute for Health Research
Department NIHR Clinical Academic Training Pathway
Country United Kingdom 
Sector Public 
PI Contribution Excellent presentations from our existing trainees.
Collaborator Contribution Excellent presentations from our existing trainees. Prospective collaborations.
Impact TBD
Start Year 2015
 
Description EULAR Task Force on Therapeutic Monitoring of Biologics 
Organisation Hospital de Madrid
PI Contribution Chair the Study Group. Proposed EULAR Task Force with multiple academic and industry partners.
Collaborator Contribution TBD
Impact TBD
Start Year 2019
 
Description EULAR Task Force on Therapeutic Monitoring of Biologics 
Organisation Manchester University
PI Contribution Chair the Study Group. Proposed EULAR Task Force with multiple academic and industry partners.
Collaborator Contribution TBD
Impact TBD
Start Year 2019
 
Description EULAR Task Force on Therapeutic Monitoring of Biologics 
Organisation NHS London
Country United Kingdom 
Sector Public 
PI Contribution Chair the Study Group. Proposed EULAR Task Force with multiple academic and industry partners.
Collaborator Contribution TBD
Impact TBD
Start Year 2019
 
Description EULAR Task Force on Therapeutic Monitoring of Biologics 
Organisation Oslo University Hospital
Country Norway 
Sector Academic/University 
PI Contribution Chair the Study Group. Proposed EULAR Task Force with multiple academic and industry partners.
Collaborator Contribution TBD
Impact TBD
Start Year 2019
 
Description EULAR Task Force on Therapeutic Monitoring of Biologics 
Organisation Reade
Country Netherlands 
Sector Hospitals 
PI Contribution Chair the Study Group. Proposed EULAR Task Force with multiple academic and industry partners.
Collaborator Contribution TBD
Impact TBD
Start Year 2019
 
Description EULAR Task Force on Therapeutic Monitoring of Biologics 
Organisation Regional University Hospital of Tours
PI Contribution Chair the Study Group. Proposed EULAR Task Force with multiple academic and industry partners.
Collaborator Contribution TBD
Impact TBD
Start Year 2019
 
Description EULAR Task Force on Therapeutic Monitoring of Biologics 
Organisation Sanquin
Country Netherlands 
Sector Charity/Non Profit 
PI Contribution Chair the Study Group. Proposed EULAR Task Force with multiple academic and industry partners.
Collaborator Contribution TBD
Impact TBD
Start Year 2019
 
Description EULAR Task Force on Therapeutic Monitoring of Biologics 
Organisation St. George Hospital
PI Contribution Chair the Study Group. Proposed EULAR Task Force with multiple academic and industry partners.
Collaborator Contribution TBD
Impact TBD
Start Year 2019
 
Description EULAR Task Force on Therapeutic Monitoring of Biologics 
Organisation University of Amsterdam
Country Netherlands 
Sector Academic/University 
PI Contribution Chair the Study Group. Proposed EULAR Task Force with multiple academic and industry partners.
Collaborator Contribution TBD
Impact TBD
Start Year 2019
 
Description IMI consortium RT-CURE 
Organisation Apitope
Country Belgium 
Sector Private 
PI Contribution As a consequence of AuToDeCRA, we have been invited to partipicate in an EU-IMI proposal for tolerance-inducing therapies in rheumatic disease. Newcastle continues to contribute to the WP6 and related clinical WP6 work packages. AuToDeCRA 2 supported. Attendance at scientific meetings. Recommendations in development for regulatory discussion.
Collaborator Contribution Active contributions from all partners.
Impact The initial output will be a funding application. Monograph of Tolerising Therapies in preparation. Regulatory position statement in development.
Start Year 2015
 
Description IMI consortium RT-CURE 
Organisation Bristol-Myers Squibb
Country United States 
Sector Private 
PI Contribution As a consequence of AuToDeCRA, we have been invited to partipicate in an EU-IMI proposal for tolerance-inducing therapies in rheumatic disease. Newcastle continues to contribute to the WP6 and related clinical WP6 work packages. AuToDeCRA 2 supported. Attendance at scientific meetings. Recommendations in development for regulatory discussion.
Collaborator Contribution Active contributions from all partners.
Impact The initial output will be a funding application. Monograph of Tolerising Therapies in preparation. Regulatory position statement in development.
Start Year 2015
 
Description IMI consortium RT-CURE 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution As a consequence of AuToDeCRA, we have been invited to partipicate in an EU-IMI proposal for tolerance-inducing therapies in rheumatic disease. Newcastle continues to contribute to the WP6 and related clinical WP6 work packages. AuToDeCRA 2 supported. Attendance at scientific meetings. Recommendations in development for regulatory discussion.
Collaborator Contribution Active contributions from all partners.
Impact The initial output will be a funding application. Monograph of Tolerising Therapies in preparation. Regulatory position statement in development.
Start Year 2015
 
Description IMI consortium RT-CURE 
Organisation Johnson & Johnson
Country United States 
Sector Private 
PI Contribution As a consequence of AuToDeCRA, we have been invited to partipicate in an EU-IMI proposal for tolerance-inducing therapies in rheumatic disease. Newcastle continues to contribute to the WP6 and related clinical WP6 work packages. AuToDeCRA 2 supported. Attendance at scientific meetings. Recommendations in development for regulatory discussion.
Collaborator Contribution Active contributions from all partners.
Impact The initial output will be a funding application. Monograph of Tolerising Therapies in preparation. Regulatory position statement in development.
Start Year 2015
 
Description IMI consortium RT-CURE 
Organisation Karolinska Institute
Country Sweden 
Sector Academic/University 
PI Contribution As a consequence of AuToDeCRA, we have been invited to partipicate in an EU-IMI proposal for tolerance-inducing therapies in rheumatic disease. Newcastle continues to contribute to the WP6 and related clinical WP6 work packages. AuToDeCRA 2 supported. Attendance at scientific meetings. Recommendations in development for regulatory discussion.
Collaborator Contribution Active contributions from all partners.
Impact The initial output will be a funding application. Monograph of Tolerising Therapies in preparation. Regulatory position statement in development.
Start Year 2015
 
Description IMI consortium RT-CURE 
Organisation Leibniz Association
Department German Rheumatism Research Centre
Country Germany 
Sector Charity/Non Profit 
PI Contribution As a consequence of AuToDeCRA, we have been invited to partipicate in an EU-IMI proposal for tolerance-inducing therapies in rheumatic disease. Newcastle continues to contribute to the WP6 and related clinical WP6 work packages. AuToDeCRA 2 supported. Attendance at scientific meetings. Recommendations in development for regulatory discussion.
Collaborator Contribution Active contributions from all partners.
Impact The initial output will be a funding application. Monograph of Tolerising Therapies in preparation. Regulatory position statement in development.
Start Year 2015
 
Description IMI consortium RT-CURE 
Organisation Leiden University Medical Center
Department Department of Rheumatology
Country Netherlands 
Sector Academic/University 
PI Contribution As a consequence of AuToDeCRA, we have been invited to partipicate in an EU-IMI proposal for tolerance-inducing therapies in rheumatic disease. Newcastle continues to contribute to the WP6 and related clinical WP6 work packages. AuToDeCRA 2 supported. Attendance at scientific meetings. Recommendations in development for regulatory discussion.
Collaborator Contribution Active contributions from all partners.
Impact The initial output will be a funding application. Monograph of Tolerising Therapies in preparation. Regulatory position statement in development.
Start Year 2015
 
Description IMI consortium RT-CURE 
Organisation Pfizer Inc
Country United States 
Sector Private 
PI Contribution As a consequence of AuToDeCRA, we have been invited to partipicate in an EU-IMI proposal for tolerance-inducing therapies in rheumatic disease. Newcastle continues to contribute to the WP6 and related clinical WP6 work packages. AuToDeCRA 2 supported. Attendance at scientific meetings. Recommendations in development for regulatory discussion.
Collaborator Contribution Active contributions from all partners.
Impact The initial output will be a funding application. Monograph of Tolerising Therapies in preparation. Regulatory position statement in development.
Start Year 2015
 
Description IMI consortium RT-CURE 
Organisation Royal Berkshire Hospital
Department Rheumatology Department
Country United Kingdom 
Sector Hospitals 
PI Contribution As a consequence of AuToDeCRA, we have been invited to partipicate in an EU-IMI proposal for tolerance-inducing therapies in rheumatic disease. Newcastle continues to contribute to the WP6 and related clinical WP6 work packages. AuToDeCRA 2 supported. Attendance at scientific meetings. Recommendations in development for regulatory discussion.
Collaborator Contribution Active contributions from all partners.
Impact The initial output will be a funding application. Monograph of Tolerising Therapies in preparation. Regulatory position statement in development.
Start Year 2015
 
Description IMI consortium RT-CURE 
Organisation Sanofi
Country Global 
Sector Private 
PI Contribution As a consequence of AuToDeCRA, we have been invited to partipicate in an EU-IMI proposal for tolerance-inducing therapies in rheumatic disease. Newcastle continues to contribute to the WP6 and related clinical WP6 work packages. AuToDeCRA 2 supported. Attendance at scientific meetings. Recommendations in development for regulatory discussion.
Collaborator Contribution Active contributions from all partners.
Impact The initial output will be a funding application. Monograph of Tolerising Therapies in preparation. Regulatory position statement in development.
Start Year 2015
 
Description IMI consortium RT-CURE 
Organisation UCB Pharma
Country United Kingdom 
Sector Private 
PI Contribution As a consequence of AuToDeCRA, we have been invited to partipicate in an EU-IMI proposal for tolerance-inducing therapies in rheumatic disease. Newcastle continues to contribute to the WP6 and related clinical WP6 work packages. AuToDeCRA 2 supported. Attendance at scientific meetings. Recommendations in development for regulatory discussion.
Collaborator Contribution Active contributions from all partners.
Impact The initial output will be a funding application. Monograph of Tolerising Therapies in preparation. Regulatory position statement in development.
Start Year 2015
 
Description IMI consortium RT-CURE 
Organisation University Hospital Erlangen
Department Department of Rheumatology and Immunology
Country Germany 
Sector Academic/University 
PI Contribution As a consequence of AuToDeCRA, we have been invited to partipicate in an EU-IMI proposal for tolerance-inducing therapies in rheumatic disease. Newcastle continues to contribute to the WP6 and related clinical WP6 work packages. AuToDeCRA 2 supported. Attendance at scientific meetings. Recommendations in development for regulatory discussion.
Collaborator Contribution Active contributions from all partners.
Impact The initial output will be a funding application. Monograph of Tolerising Therapies in preparation. Regulatory position statement in development.
Start Year 2015
 
Description IMI consortium RT-CURE 
Organisation University of Bath
Department Rheumatology
Country United Kingdom 
Sector Academic/University 
PI Contribution As a consequence of AuToDeCRA, we have been invited to partipicate in an EU-IMI proposal for tolerance-inducing therapies in rheumatic disease. Newcastle continues to contribute to the WP6 and related clinical WP6 work packages. AuToDeCRA 2 supported. Attendance at scientific meetings. Recommendations in development for regulatory discussion.
Collaborator Contribution Active contributions from all partners.
Impact The initial output will be a funding application. Monograph of Tolerising Therapies in preparation. Regulatory position statement in development.
Start Year 2015
 
Description IMI consortium RT-CURE 
Organisation University of Birmingham
Department Institute of Cancer and Genomic Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution As a consequence of AuToDeCRA, we have been invited to partipicate in an EU-IMI proposal for tolerance-inducing therapies in rheumatic disease. Newcastle continues to contribute to the WP6 and related clinical WP6 work packages. AuToDeCRA 2 supported. Attendance at scientific meetings. Recommendations in development for regulatory discussion.
Collaborator Contribution Active contributions from all partners.
Impact The initial output will be a funding application. Monograph of Tolerising Therapies in preparation. Regulatory position statement in development.
Start Year 2015
 
Description IMI consortium RT-CURE 
Organisation University of Glasgow
Department Department of Rheumatology
Country United Kingdom 
Sector Academic/University 
PI Contribution As a consequence of AuToDeCRA, we have been invited to partipicate in an EU-IMI proposal for tolerance-inducing therapies in rheumatic disease. Newcastle continues to contribute to the WP6 and related clinical WP6 work packages. AuToDeCRA 2 supported. Attendance at scientific meetings. Recommendations in development for regulatory discussion.
Collaborator Contribution Active contributions from all partners.
Impact The initial output will be a funding application. Monograph of Tolerising Therapies in preparation. Regulatory position statement in development.
Start Year 2015
 
Description IMI consortium RT-CURE 
Organisation University of Queensland
Country Australia 
Sector Academic/University 
PI Contribution As a consequence of AuToDeCRA, we have been invited to partipicate in an EU-IMI proposal for tolerance-inducing therapies in rheumatic disease. Newcastle continues to contribute to the WP6 and related clinical WP6 work packages. AuToDeCRA 2 supported. Attendance at scientific meetings. Recommendations in development for regulatory discussion.
Collaborator Contribution Active contributions from all partners.
Impact The initial output will be a funding application. Monograph of Tolerising Therapies in preparation. Regulatory position statement in development.
Start Year 2015
 
Description Kennedy Institute, Oxford University 
Organisation University of Oxford
Department Kennedy Institute of Rheumatology
Country United Kingdom 
Sector Academic/University 
PI Contribution Presentation Towards a Cure for Rheumatoid Arthritis
Collaborator Contribution Feedback and small group discussions with individual PIs and researchers.
Impact Plans for future collaborative research through RACE.
Start Year 2018
 
Description RACE Scientific Meeting, Newcastle, 2018 
Organisation University of Birmingham
Department Birmingham University Imaging Centre (BUIC)
Country United Kingdom 
Sector Academic/University 
PI Contribution Hosted by Newcastle. Showcase collaborative opportunities with presentations by Andy Mellor, Shoba Amarnath, Andy Filby together with clinical research updates.
Collaborator Contribution All contributed actively and gave valuable feedback.
Impact Scientific strategic planning outputs and plans for further collaboration.
Start Year 2015
 
Description RACE Scientific Meeting, Newcastle, 2018 
Organisation University of Glasgow
Department Mental Health Rights Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution Hosted by Newcastle. Showcase collaborative opportunities with presentations by Andy Mellor, Shoba Amarnath, Andy Filby together with clinical research updates.
Collaborator Contribution All contributed actively and gave valuable feedback.
Impact Scientific strategic planning outputs and plans for further collaboration.
Start Year 2015
 
Description RACE Scientific Meeting, Newcastle, 2018 
Organisation University of Oxford
Department Kennedy Institute of Rheumatology
Country United Kingdom 
Sector Academic/University 
PI Contribution Hosted by Newcastle. Showcase collaborative opportunities with presentations by Andy Mellor, Shoba Amarnath, Andy Filby together with clinical research updates.
Collaborator Contribution All contributed actively and gave valuable feedback.
Impact Scientific strategic planning outputs and plans for further collaboration.
Start Year 2015
 
Title Biomarker for Remission of Rheumatoid Arthritis 
Description Gene signature predicting drug-free remission. 
IP Reference  
Protection Copyrighted (e.g. software)
Year Protection Granted 2017
Licensed No
Impact Biomarker for Remission of Rheumatoid Arthritis UK patent application number 1805685.3 Prompted BIO-FLARE trial. Validation study in progress.
 
Title BIOlogical Factors that Limit sustAined Remission in rhEumatoid arthritis (BIO-FLARE) 
Description Identifying pathways that underpin disease flare in RA. IRAS ID for the trial is 234030. Also see: https://gtr.ukri.org/projects?ref=MR%2FN026977%2F1 
Type Management of Diseases and Conditions
Current Stage Of Development Initial development
Year Development Stage Completed 2018
Development Status Actively seeking support
Impact TBD 
URL https://gtr.ukri.org/projects?ref=MR%2FN026977%2F1
 
Description 4th International Workshop on Therapeutic Tolerancing 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Every 4 years Newcastle University hosts its international workshop on Clinical Therapeutic Tolerance. Previous editions covered 'Therapeutic Tolerance: Myth or Reality?' (2005), 'Therapeutic Tolerance: Closer to Reality?' (2009) and 'Therapeutic Tolerance: Tolerance Inducing Strategies in the Clinic'. (2013)

Our fourth workshop carried the title 'Therapeutic Tolerance: First-in-Human Data' and was held from 27th - 30th June 2017. Main focus of the meeting was the analysis of data from the first therapeutic tolerance trials.

The popular programme allows ample time for discussion and true debate, with an opportunity for poster presentations (with prizes). This international workshop is attended by leading scientists and practitioners in the field from around the world.
Year(s) Of Engagement Activity 2017
URL https://www.newcastlebrc.nihr.ac.uk/news/therapeutic-tolerance-first-human-data-event/
 
Description ADARRC - RA Summit - Abu Dhabi 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The 7th annual Abu Dhabi Advanced Rheumatology Review Course provided a comprehensive update on adult and paediatric rheumatology. Designed as a three-day, intensive rheumatology course, ADARRC is a series of lectures and workshops delivered by global experts to provide new insights, case studies and pioneering research findings.
Year(s) Of Engagement Activity 2017
URL http://adarrc.org/
 
Description ARUK RACE Annual Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The RA Centre of Excellence in RA pathogenesis is an infrastructure award from Arthritis Research UK that supports a collaboration between Newcastle, Birmingham and Glasgow. We write grants together, support a cadre of PhD students and engage with patients and carers. We meet face to face three times per year.
Year(s) Of Engagement Activity 2017
URL http://www.race-gbn.org/
 
Description ARUK RACE Meeting - Glasgow 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The RA Centre of Excellence in RA pathogenesis is an infrastructure award from Arthritis Research UK that supports a collaboration between Newcastle, Birmingham and Glasgow. We write grants together, support a cadre of PhD students and engage with patients and carers.
Year(s) Of Engagement Activity 2017
URL http://www.race-gbn.org/
 
Description ARUK RACE Scientific Meeting - Birmingham 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The RA Centre of Excellence in RA pathogenesis is an infrastructure award from Arthritis Research UK that supports a collaboration between Newcastle, Birmingham and Glasgow. We write grants together, support a cadre of PhD students and engage with patients and carers.
Year(s) Of Engagement Activity 2017
URL http://www.race-gbn.org/
 
Description ARUK RACE Scientific Meeting - Newcastle 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The RA Centre of Excellence in RA pathogenesis is an infrastructure award from Arthritis Research UK that supports a collaboration between Newcastle, Birmingham and Glasgow. We write grants together, support a cadre of PhD students and engage with patients and carers.
Year(s) Of Engagement Activity 2017
URL http://www.race-gbn.org/
 
Description ARUK T-reg Workshop, London, 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Supporters
Results and Impact A workshop that involved several charities and international experts. The goal to promote collaborative research and funding around the role of Tregs in autoimmune diseases.
Year(s) Of Engagement Activity 2018
 
Description ARUK strategy meeting - Chesterfield 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Supporters
Results and Impact A meeting to update us on the charity (Arthritis Research UK), and particularly its recent merger with Arthritis Care. Also a useful discussion around future research directions.
Year(s) Of Engagement Activity 2017
URL http://www.arthritisresearchuk.org/
 
Description CLUSTER Consortium - London, 2018 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact Strategic plans for MRC-funded stratified medicine programme in JIA and associated Uveitis. JDI chairs the external SAB.
Year(s) Of Engagement Activity 2018
URL https://juvenilearthritisnews.com/2018/04/02/cluster-consortium-aims-improve-jia-uveitis-patients-li...
 
Description CRUK-ARUK Immune Homeostasis Innovation Workshop - Oxford 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Researchers and clinicians sharing information on homeostatic mechanisms in immunological systems.
Year(s) Of Engagement Activity 2017
URL http://www.arthritisresearchuk.org/research/news-for-researchers/2018/january/funding-partnership-wi...
 
Description EULAR 2019 Organizing Committee 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Preparing for EULAR 2019 (Madrid). JDI is Abstracts Chair, a majpr role in the organising committee..
Year(s) Of Engagement Activity 2018,2019
URL https://www.congress.eular.org
 
Description EULAR AGM planning meeting, Zurich 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This is the committee that plans the annual scientific meeting for the European League Against Rheumatism.
Year(s) Of Engagement Activity 2017
URL http://www.eular.org
 
Description EULAR Research Centre, London, 2019 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Strategic discussions around a prospective, collaborative, virtual research centre for European Rheumatic and Musculoskeletal Disorders groups.
Year(s) Of Engagement Activity 2019
 
Description EULAR Scientific Committee - Amsterdam 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This is the committee that plans the annual scientific meeting for the European League Against Rheumatism. I am the chair of this committee from 2018-2020.
Year(s) Of Engagement Activity 2018
URL http://www.congress.eular.org/?utm_source=google&utm_medium=cpc&utm_campaign=registration&gclid=CjwK...
 
Description EULAR Scientific Programme Committee 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Planning meeting for EULAR 2019 in Madrid. As Abstract Chair I play a major role in this meeting.
Year(s) Of Engagement Activity 2018
URL http://congress.eular.org/index.cfm
 
Description EULAR Therapeutic Drug Monitoring Study Group, Amsterdam, 2018 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Chaired this EULAR Study Group reviewing therapeutic drug monitoring. Decision taken to apply for EULAR Task Force status in 2019.
Year(s) Of Engagement Activity 2018
URL https://www.eular.org/clinical_affairs_study_groups.cfm
 
Description European Workshop for Rheumatology Research, Lyon, 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Annual research workshop, provides the opportunity for postgrad students and ECRs to present their work to an international audience. One of our students had an oral presentation and another presented a poster.
Year(s) Of Engagement Activity 2019
URL http://www.ewrr.org/
 
Description Gabriel Panayi Feschrift, Kings College, London, 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Feschrift for Gabriel Panayi. Presentation on therapeutic tolerance induction. Approached by arthritis patient and member of the public with a view to collaboration.
Year(s) Of Engagement Activity 2018
 
Description Guardian Newspaper 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Contributed to an article focussed on the emergence of autoimmunity in patients with cancer taking checkpoint inhibitors
Year(s) Of Engagement Activity 2018
URL http://bit.ly/2tdMLnc
 
Description International Forum for RA 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The International Forum for RA is a meeting focussed on cutting edge research in rheumatoid arthritis, with an emphasis on influencing future management strategies. I gave a presentation around 'smart trial designs'. This led to a new collaboration with Dana Orange (Rockefeller).
Year(s) Of Engagement Activity 2017
 
Description MRC DPFS Meeting - London 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The DPFS scheme is a key part of the MRC's Translational Research Strategy and supports the translation of fundamental discoveries toward benefits to human health. It funds the pre-clinical development and early clinical testing of novel therapeutics, devices and diagnostics, including "repurposing" of existing therapies.
Remit
The scheme supports academically led projects whose goals are to improve prevention, diagnosis, prognosis, or treatment of significant health needs, or that focus on developing research tools that increase the efficiency of developing interventions.
Year(s) Of Engagement Activity 2018
URL https://www.mrc.ac.uk/funding/browse/biomedical-catalyst-dpfs/biomedical-catalyst-developmental-path...
 
Description MRC Newcastle University Visit 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Supporters
Results and Impact Review and round table discussions of Newcastle University research outputs and statistics.
Year(s) Of Engagement Activity 2018
 
Description MRC Stratified Medicine, London, 2018 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact Review of progress for the MRC Stratified Medicine Consortia and Pathology Nodes.
Year(s) Of Engagement Activity 2018
 
Description MRC TRG Meeting - London 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The MRC Translational Research Group (TRG) is responsible for ensuring strong continued support for translational research across the MRC. It supports translational research across MRC funding Boards and Panels, through partnerships with other funders and major Higher Education Institutions and through dedicated funding schemes. Areas of particular focus for TRG include:
The Biomedical Catalyst, an integrated translational funding programme jointly operated with Innovate UK (formerly the Technology Strategy Board).
The Confidence in Concept scheme, supporting academically led feasibility research at the institutional level.
The Developmental Pathway Funding Scheme, part of the Biomedical Catalyst, supporting translation of fundamental discoveries toward benefits to human health.
The Methodology Research Programme, in partnership with the National Institute for Health Research (NIHR).
Coordination with the MRC-NIHR Efficacy and Mechanism Evaluation Programme (EME) programme and other NIHR funding schemes to ensure suitable projects progress to late-stage trials.
Year(s) Of Engagement Activity 2017
URL https://www.mrc.ac.uk/about/our-structure/strategy-board-overview-groups/translational-research-grou...
 
Description NE Regional Meeting - Newcastle 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Regional Newcastle Meeting of Rheumatology Professionals, focussed on early rheumatoid arthritis and at risk individuals. I presented on tolerance-inducing strategies
Year(s) Of Engagement Activity 2017,2018
 
Description NICE Diagnostic Advisory Committe, Manchester, 2019 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Development of draft recommendations on Therapeutic monitoring of TNF-alpha inhibitors in rheumatoid arthritis. These will be published for public consultation before formal recommendations are published.
Year(s) Of Engagement Activity 2019
 
Description NIHR BRC Impact Showcase, Newcastle, 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Showcase event attended by senior figures from the Department of Health and major charities including Versus Arthritis. The CEOs of the Trust and University attended. Musculoskeletal presentations included patient presentations and videos. Ken Baker was awarded a prize for best oral presentation. Sir John Burn and Dame Jackie Daniel presented their vision for Newcastle.
Year(s) Of Engagement Activity 2018
URL https://www.newcastlebrc.nihr.ac.uk/events/nihr-newcastle-biomedical-research-centre-impact-showcase...
 
Description NIHR Biomedical Research Centre Directors Meeting - London 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Discussions around expectations for the newly funded NIHR BRCs..
Year(s) Of Engagement Activity 2017
URL https://www.nihr.ac.uk/about-us/how-we-are-managed/our-structure/infrastructure/biomedical-research-...
 
Description RACE Scientific Meeting - Glasgow 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The RA Centre of Excellence in RA pathogenesis is an infrastructure award from Arthritis Research UK that supports a collaboration between Newcastle, Birmingham and Glasgow. We write grants together, support a cadre of PhD students and engage with patients and carers. This was the annual scientific meeting.
Year(s) Of Engagement Activity 2017
URL http://www.race-gbn.org/
 
Description RACE Scientific Meeting, Birmingham, 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Scientific updates including progress with TRAFIC and BioFLARE.
Year(s) Of Engagement Activity 2018
 
Description RACE Second International Scientific Advisory Board Meeting, Glasgow, 2018 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact Scientific presentations and patient-focused discussions. Excellent feedback from the panel, which has influenced.renewal plans.
Year(s) Of Engagement Activity 2018
URL http://www.race-gbn.org/communityengagement/
 
Description RT-CURE Annual Meeting, Beerse, 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact Annual meeting of the RT-CURE consortium. Excellent meeting with welcome patient partner participation.
Year(s) Of Engagement Activity 2018
 
Description Royal College of Physicians of Edinburgh Therapeutic Drug Monitoring Conference, Edinburgh, 2018 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Workshop focussed on therapeutic drug monitoring for biologic therapies including round table discussion and establishment of a working group.
Year(s) Of Engagement Activity 2018