Maximising Therapeutic Utility for Rheumatoid Arthritis using genetic and genomic tissue responses to stratify medicines.

Lead Research Organisation: Queen Mary, University of London
Department Name: William Harvey Research Institute

Abstract

Rheumatoid arthritis (RA) is a disease in which inflammation of joints can cause pain, stiffness, lasting damage and disability. It affects an estimated 500,000 people in the UK and has important impacts on their lives. For example, within 5 years of diseases onset, 33% people are unable to remain in full-time work.
There have been dramatic advances in treatment of RA in recent years. First, patients are treated with drugs as soon as they are diagnosed with RA and the dose is increased quickly to try and suppress all joint inflammation. The most common drug used is called methotrexate (MTX). Second, those people who fail to respond to MTX can be given a biologic drug, so-called because they inhibit a biological pathway involved in inflammation. There are a number of biologic drugs that can be used; most commonly, anti-tumour necrosis factor (TNF) therapies are used as the first choice biologic. Patients who fail to respond to those are then switched to try a biologic drug that acts by removing B cells from the circulation (rituximab, RTX). More recently, a biologic drug that acts by blocking another inflammatory pathway, the IL6 pathway, has been recommended for use (tocilizumab, TOC). Whilst each of these drugs has been proven to control inflammation and slow or prevent lasting joint damage, they don't work for every patient. Thus, 45% patients fail to respond to MTX whilst 30-40% fail to respond to each of the biologic drugs. At the moment, we have no means of predicting which patients will respond best to which drug and so the drugs are prescribed on a 'trial and error' basis. However, we know that the longer it takes to find an effective therapy, the more joint damage accumulates and the worse the long-term outlook is for patients. Therefore, the aim of this study is to identify predictors of response to MTX, anti-TNF, RTX and TOC so that patients with RA can be given the drug that they are most likely to respond to, as soon as they are diagnosed.
The response predictors may be changes in DNA, proteins or other molecules and these changes may be detectable in blood samples or in the joint tissues that are inflamed. In this program of work, we plan a comprehensive series of experiments to investigate this. We will study both tissue samples taken from the joints of patients with RA as well as blood samples collected from large numbers of RA patients treated with each of the 4 drugs to be investigated. We will study genetic changes, protein levels and other molecules. We will combine the information obtained to test whether combinations of markers predict response better than studying one marker at a time. We already have evidence to suggest that the number of B cells in the inflamed joint tissue can predict whether patients are likely to respond well to the B cell depleting therapy, RTX. Therefore, we also plan to test how well this works in practice by performing a randomized clinical trial whereby patients will be randomly assigned to receive RTX or another biologic therapy based on the level of B cell infiltration seen in their joint tissue.
The outcome of this study will be the identification of blood or tissue markers that help to target the right treatments to the right patients with RA. This is particularly important because the biologic drugs are very expensive (£8-10,000 per patient per year). Crucially, as the annual cost of biologics to the NHS is ~£160 million, the identification of the 30-40% of non-responders prior to "blind" therapy would potentially save £13-18 million annually because approximately 4-5,000 patients start anti-TNF therapy each year in the UK.

Technical Summary

Research objectives: Two parallel workstrands (WS) will investigate synovial tissue and blood correlates (WS.1) and large scale blood based screening (WS.2) to identify biomarkers of response to four drugs which from the main steps in treatment escalation in rheumatoid arthritis (RA): methotrexate (MTX), anti-tumour necrosis factor (anti-TNF) and rituximab (RTX) and tocilizumab (TOC).
Methodology and experimental design: WS.1: We shall search for tissue-driven biomarkers and blood correlates in the largest synovial tissue biobank of this type (2 time points 0 & 6 months biopsy) in the world & clinical datasets (over 200 patients immediately available). In addition, in a prospective randomised clinical trial (adaptive design) we will test the hypothesis that discrete cellular and molecular signatures in the synovial tissue ("pathotypes") will enrich for response to existing biologic therapies. WS.2: we will take advantage of the large observational cohorts of patient samples either already collected or which could be collected for minimal cost to undertake a comprehensive analysis to identify that will reliably identify responders/non-responders to each of the drugs. These collections include biological samples from over 3,000 anti-TNF-, 1,500 MTX- and 1,200 RTX-treated subjects.
Proposed techniques and approaches: The two WSs are fully integrated through "multi-omic" approaches that constitute cross-cutting themes (CTs) incorporating genetic, genomic, transcriptomic, and proteomic studies. Both WSs converge in a large analytical and modelling package driven by experts in Bioinformatics and Statistics to identify individual or, more likely, a combination of factors that predict treatment response to each of the four drugs. A preliminary health economic assessment of identified biomarkers will also be undertaken.
Exploitation of results: In collaboration with our Industry partners we have drawn up plans to commercialize potential diagnostics for patient benefit

Planned Impact

Commercial beneficiaries:
Immediate commercial beneficiaries are the commercial parties of this consortium including large pharma e.g. Amgen, Pfizer, UCB Pharma, Pfizer, diagnostics companies e.g Qiagen and small biotech e.g. Activiomics.

We have developed a strong industry engagement network that has led to a major Industry response with firm intellectual, in-kind and financial contributions from 10 commercial partners (see MICA forms). Industrial partners have been selected to provide expertise in their areas of research, development and commercialisation, as global leaders in the field of therapeutic and (companion) diagnostic development.

Testing of the biomarker will have to be standardized before widespread introduction into clinical practice. Thus commercial diagnostics companies will benefit from development of a point-of-care companion diagnostic or delivery of a clinical test in a CLIA lab. Our industry collaborators will provide a means to facilitate direct engagement with large pharmaceutical companies and SMEs.

Policy makers: Given the expense of biologic drugs and their significant failure rate, policy makers will benefit from this research. Thus our data will contribute to assessments by the National Institute of Health and Clinical Excellence (NICE) to optimize and rationalize treatment for RA.

Patient and public beneficiaries: Ultimately, patients should benefit from this research because it will enable them to be treated earlier in their care pathway with a drug that is most likely to induce remission of symptoms and least likely to induce serious adverse events. This will have downstream consequences for employment and care providers thus having a wider social and economic impact.

Publications

10 25 50

publication icon
Barton A (2017) Stratified medicine in rheumatoid arthritis-the MATURA programme. in Rheumatology (Oxford, England)

publication icon
Bombardieri M (2017) Ectopic lymphoid neogenesis in rheumatic autoimmune diseases. in Nature reviews. Rheumatology

publication icon
Corsiero E (2016) Ectopic Lymphoid Structures: Powerhouse of Autoimmunity. in Frontiers in immunology

publication icon
David T (2018) Genetics of immune-mediated inflammatory diseases. in Clinical and experimental immunology

 
Title Tate Exchange Programme (Jun 2019) 
Description Exhibition to demonstrate the 'Effect of Arthritis on Movement and Art' Gloves will be used to restrict movement and simulate the effects of arthritis Ultrasound machines will show delegates the inside of their joints Art from patients with arthritis (including Renoir ) will be displayed The role of research in the development of new medicines and the alleviation of symptoms will be highlighted 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2019 
Impact Too early 
URL https://www.tate.org.uk/visit/tate-modern/tate-exchange
 
Description 21st Annual International Advances in Targeted Therapies meeting (28-30 March 2019)
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
URL https://ard.bmj.com/content/79/1/88
 
Description ACR/eular Exchange Program
Geographic Reach Europe 
Policy Influence Type Influenced training of practitioners or researchers
 
Description AMP RA SLE Steering Committee
Geographic Reach North America 
Policy Influence Type Participation in a advisory committee
URL https://www.nih.gov/research-training/accelerating-medicines-partnership-amp
 
Description Addressing the grand challenges in Immune Mediated Inflammatory Diseases
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Annual EATC/EOTC Directors Meeting - Arthritis Research UK
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description Arthritis Research UK Rare Diseases Workshop 2017
Geographic Reach National 
Policy Influence Type Participation in a national consultation
 
Description Arthritis Research UK and NIHR sponsored Experimental Musculoskeletal Medicine Conference - to explore the alignment and opportunities to maximise, improve and add to the UK musculoskeletal experimental medicine investment in order to accelerate the translation of innovations for the benefit of patients, the public and the healthcare system
Geographic Reach National 
Policy Influence Type Participation in a national consultation
 
Description Development of immune tolerance therapies for the treatment of rheumatic diseases - THE INNOVATIVE MEDICINES INITIATIVE
Geographic Reach Europe 
Policy Influence Type Membership of a guideline committee
URL http://www.imi.europa.eu
 
Description EULAR Synovitis Study Group
Geographic Reach Europe 
Policy Influence Type Membership of a guideline committee
URL http://www.eular.org/investigative_rheumatology_study_groups.cfm
 
Description Influence on Funding Policy: MRC, NIHR, ARUK recognised need to fund Stratified Medicine Programmes in RA. PEAC has formed the platform for a suite of stratified Medicine programmes including MATURA and R4RA
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Joint NIHR CRN/UK Pharmacogenetics & Stratified Medicine Network Workshop. A Roadmap for Delivery of Stratified Medicine Research within the NHS (Nov 16)
Geographic Reach National 
Policy Influence Type Participation in a national consultation
 
Description Joint Translation Research Collaboration meeting 25th March 2019
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Guideline Title Guideline on drug monitoring in rheumatoid arthritis
Description Lead Specialist Committee member on NICE Diagnostic Advisory Committee
Geographic Reach National 
Policy Influence Type Citation in clinical guidelines
 
Description MRC Population and Systems Medicine Board
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Newcastle Audit Meeting
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
 
Description TRC Strategy Review /Objectives Setting
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
URL https://www.nihr.ac.uk/life-sciences-industry/access-to-expertise-and-collaborations/collaborations-...
 
Description Training in Disease Activity Scores & Ultrasound Assessments of RA
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact Greater consistency in evaluating and recording of measures of disease in RA
 
Description Translational Research Collaboration for Joint & related inflammatory diseases- Steering Committee Meeting
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
URL http://www.nihr.ac.uk/life-sciences-industry/access-to-expertise-and-collaborations/collaborations-f...
 
Description Ultrasound Guided Synovial Biopsy Courses
Geographic Reach Europe 
Policy Influence Type Influenced training of practitioners or researchers
URL http://www.matura-mrc.whri.qmul.ac.uk/ultrasound_guided_synovial_biopsy_taking_a_biopsy.php
 
Description United Rheumatology Meeting - Biomarker Expert Panel (Jan2020)
Geographic Reach North America 
Policy Influence Type Participation in a advisory committee
 
Description VERSUS ARTHRITIS ANNUAL FELLOWS' MEETING 2019 (14-15March 2019)- Chair of a main session & ran 'meet the expert' session
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
URL https://www.versusarthritis.org/research/research-funding-and-policy/fellowships-and-career-support/...
 
Description Versus Arthritis senior stakeholder meeting
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description ARUK- Special Strategic Award
Amount £12,000 (GBP)
Funding ID 20670 
Organisation Versus Arthritis 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2016 
End 03/2019
 
Description Arthritis Research UK Centre of Excellence in Genetics and Genomics
Amount £1,999,950 (GBP)
Funding ID 21754 
Organisation Versus Arthritis 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2018 
End 07/2023
 
Description Arthritis Research UK Clinical lecturer in experimental medicine and rheumatology
Amount £565,973 (GBP)
Funding ID 21890 
Organisation Versus Arthritis 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2018 
End 01/2023
 
Description Arthritis Research UK project grant
Amount £253,210 (GBP)
Funding ID 21818 
Organisation Versus Arthritis 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2018 
End 04/2021
 
Description Confidence in Concept: Novel Fc mutants to fine tune therapeutic monoclonal antibody functions by altering Fc?R binding
Amount £75,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2020 
End 10/2020
 
Description Defining the spatial requirements for therapeutic modulation of signaling through Fc?RIIa
Amount £100,000 (GBP)
Funding ID SBF004\1097 
Organisation University of Leeds 
Sector Academic/University
Country United Kingdom
Start 09/2019 
End 08/2021
 
Description European Union Marie Sklodowska-Curie - Innovative Training Network, HELICAL (HEalth data LInkage for ClinicaL benefit).
Amount € 3,166,720 (EUR)
Funding ID 813545 
Organisation EU-T0 
Sector Public
Country European Union (EU)
Start 01/2019 
End 12/2023
 
Description Immune-Mediated Inflammatory Disease Biobanks in the UK (IMIDBio-UK)
Amount £1,700,000 (GBP)
Funding ID MR/R014191/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 09/2017 
End 03/2021
 
Description Immune-mediated inflammatory disease biobanks in the UK - IMIDBio_UK
Amount £218,084 (GBP)
Funding ID MR/R014191/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 09/2017 
End 09/2020
 
Description Investigation of methotrexate metabolites in CD4+ T-Lymphocytes as a predictor of response to treatment in Rheumatoid Arthritis
Amount £263,289 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2017 
End 09/2020
 
Description MRC Confidence in Concept - Glucocorticoids and Skin Healing in Diabetes (GC-SHealD)
Amount £72,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 09/2018 
End 04/2021
 
Description MRC Proof of Concept
Amount £22,212 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2019 
End 03/2020
 
Description MRC equipment
Amount £50,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 02/2016 
End 03/2016
 
Description NIHR Clinical Lectureship
Amount £310,937 (GBP)
Organisation Health Education England 
Sector Public
Country United Kingdom
Start 01/2019 
End 01/2023
 
Description NIHR Manchester BRC
Amount £28,500,000 (GBP)
Organisation National Institute for Health Research 
Department NIHR Biomedical Research Centre
Sector Public
Country United Kingdom
Start 04/2017 
End 03/2022
 
Description NIHR/BRC
Amount £6,736,575 (GBP)
Organisation University of Leicester 
Department NIHR Biomedical Research Centre
Sector Hospitals
Country United Kingdom
Start 04/2017 
End 03/2022
 
Description Proximity to Discovery (Industrial Visit)
Amount £5,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2018 
End 06/2018
 
Description Springboard Award: Defining the spatial requirements for modulation of signaling through Fc?RIIa
Amount £99,390 (GBP)
Organisation Academy of Medical Sciences (AMS) 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2019 
End 08/2021
 
Title A statistical modelling tool for identifying patients with inflammatory diseases who are at risk of steroid toxicity 
Description We are developing this research tool with Dr Mar Pujades Rodriguez. We will use the resulting algorithms to develop a clinical tool to identify people at high risk of glucocorticoid toxicity. This tool would be used by clinicians to guide patient management, and to reduce the number of patients affected by side-effects. Robust data on side-effects and associated risk factors will improve health economic analyses to guide policymaking. It will empower patients to insist that their needs in service delivery are recognised and not neglected. This work also includes the study of risk factors for different types of toxicities and the development of risk prediction tools to identify patients with increased risk of toxicity. We have already obtained data from the Clinical Practice Research Database (linked to HES and the mortality registry) and UKBiobank and are in the process of developing algorithms to model glucocorticoid dose and duration and to develop new methodology to study less frequently investigated toxicities, such as serious infections, adrenal insufficiency in addition to diabetes, hypertension, cardiovascular disease and osteoporosis/fracture. We have also been in discussion with the Pharmaceutical Industry with a view to obtaining data on patients receiving glucocorticoids during clinical trials. Dr Mar Pujades and Dr Sarah Mackie are co-supervising a PhD student (Lana Lai, Pharmacist) to explore risk factors for the development of diabetes in patients with GCA as a result of steroid toxicity. 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2019 
Provided To Others? Yes  
Impact We have now published our results on infections and adrenal insufficiency and made these available through open access. The hypertension manuscript is in press and manuscripts on diabetes and cardiovascular complications are undergoing peer review. 
 
Title DNA extraction from formulin-fixed parafin embedded blocks and T-cell receptor sequencing 
Description A method has been developed to amplify the TCR beta region from temporal biopsy arteries embedded in FFPE from GCA patients followed by sequencing of the amplified region. It involves extracting DNA from patient temporal arteries from FFPE tissue using the Qiagen FFPE DNA extraction kit. The extracted DNA is then used to amplify the TCR V beta region using a pool of primers. The amplified band is then excised from the agarose gel, purified and used to perform a second round of amplification using indexes from the Nextera XT Indexing Kit. Following indexing, the samples are cleaned, QCed and quantified to prepare them for pooling prior to sequencing them on the MiSEq. 
Type Of Material Biological samples 
Year Produced 2018 
Provided To Others? Yes  
Impact Pilot data has shown that it is possible to amplify the TCR V beta region from DNA extracted from GCA temporal artery biopsy FFPE tissues and that the results are comparable to sequencing performed from DNA extracted from blood. We are currently undertaking an initial assessment of 20 cases. 
 
Title EMR Biobank 
Description EMR biobank containing over 800 synovial biopsies supports multiple projects and each research project adds to the samples and information available Synovial biopsies are linked to tight clinical databases including ultrasound synovitis assessments 
Type Of Material Biological samples 
Year Produced 2015 
Provided To Others? Yes  
Impact Supports academic and industry collaborations 
URL https://directory.biobankinguk.org/Profile/Biobank/GBR-1-254
 
Title Clinical Records Management System for Inflammatory Arthritis database (CReMSIA) 
Description Currently upwards of 400 patients suffering from inflammatory arthritis (predominantly Rheumatoid and Psoriatic arthritis) have been recruited primarily to synovial biopsy based studies led by the centre for Experimental Medicine and Rheumatology at Barts Health NHS Trust. Patients within the cohort have been recruited at varying disease stages including at disease onset (PEAC, Pathobiology of Early Arthritis cohort), following failure to respond to traditional disease modifying anti-rheumatic drugs (DMARDs) (THERAPIST, STRAP) and following the failure on first line biologic therapy (R4RA study). The CReMSIA database proposed intends to act as a central repository for all clinical data collected within clinical trials within the department of Rheumatology, Barts Health NHS Trust led by Experimental Medicine and Rheumatology for which QMUL is the study sponsor. The intention would be to continue to follow these patients on their return to routine NHS rheumatology clinic, collecting data recorded within routine follow up visits. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? No  
Impact Too early 
 
Title STRAP study database 
Description Study specific Electronic Data Capture (EDC) system for STRAP. This includes a electronic Case Record Form (eCRF) as well as a Study Management system linking clinical data to pathobiology data. The EDC system is designed to follow the order of the study assessments and include all the clinical data (incl. Medication history, lifestyle factors questionnaire, DAS28 etc). submission to the database is via an encrypted and password protected link dedicated to each individual centre. This database is designed to provide an online facility to monitor registration, transport and processing of STRAP samples, from the clinic to the microscope. 
Type Of Material Database/Collection of data 
Year Produced 2015 
Provided To Others? Yes  
Impact Management of the study High quality research data 
URL https://www.matura-strap-mrc.whri.qmul.ac.uk
 
Title TranSMART 
Description The TranSMART platform, which was originally developed and open sourced by our industrial partner, Janssen, is now widely used internationally for translational research (http://transmartfoundation.org/). The MRC-MATURA TranSMART has itself been developed in close collaboration with the MRC-PSORT and the MRC-RA-MAP consortium in collaboration with the Innovative Medicines Initiative (IMI) project European Translational Information and Knowledge Management Services (eTRIKS).The MRC-MATURA TranSMART is a web-based knowledge management platform that enables MATURA consortium members to develop and refine research hypotheses by investigating correlations between genetic, genomic and phenotypic data, and assessing their analytical results in the context of published literature and other work related to RA disease pathology and drug response. 
Type Of Material Database/Collection of data 
Year Produced 2015 
Provided To Others? Yes  
Impact The MRC-MATURA TranSMART infrastructure enables inte­­grated analysis towards the identification of biomarker signatures that will help researchers and clinicians better understand the different responses to biologic drugs that are seen in the clinic, ultimately offering better and more personalised treatment to those affected by rheumatoid arthritis. The MRC-MATURA TranSMART platform enables researchers to: Develop, test and refine research hypotheses Search multiple data sets for potential drug targets, pathways and biomarkers Compare data from proteomics, metabolomics and other "omics" studies Contrast patterns of gene expression in healthy and diseased individuals and tissue samples Investigate correlations between genotype and phenotype in clinical trial data Study genetic and environmental factors involved in RA Display data visually using a graphical interface Stratify clinical data into molecular subtypes of RA disease and drug response Collaborate across the academic and industrial partnership of the MATURA consortium 
 
Description Abbvie 
Organisation AbbVie Inc
Country United States 
Sector Private 
PI Contribution Research collaboration has resulted in agreement to advance knowledge transfer and data sharing between partners.
Collaborator Contribution Research collaboration has resulted in agreement to advance knowledge transfer and data sharing between partners.
Impact Research collaboration has resulted in agreement to advance knowledge transfer and data sharing between partners.
Start Year 2014
 
Description Avacta 
Organisation Avacta Group
Country United Kingdom 
Sector Private 
PI Contribution MATURA will provide samples from RA patients treated with biologics, samples from responders and non-responders will be analysed by Avacta using their Affirmer Arrays to identify candidate biomarkers.
Collaborator Contribution Avacta will provide analytical services and reagents for the analyses.
Impact Work ongoing
Start Year 2015
 
Description BGI Tech Solutions (Hong Kong) 
Organisation Beijing Genomics Institute
Country China 
Sector Academic/University 
PI Contribution Data sharing and knowledge transfer.
Collaborator Contribution Research collaboration whereby BGI provide next generation technology to analyse samples that could lead to potential companion diagnostics.
Impact To facilitate research in this area the collaboration between industry and academia is required to build an all encompassing network of UK clinical excellence. The desired output of this research collaboration would generate a new approach to clinical practice with the accelerated adoption of a personalised medicine for the benefit of patients and the national healthcare budget
Start Year 2014
 
Description Genentech/Roche 
Organisation Genentech, Inc
Country United States 
Sector Private 
PI Contribution Research collaboration and data sharing.The collaboration will enable the proposed study to be undertaken by providing drug that will allow for comparison of response within the proposed subsets of rheumatoid arthritis. In addition, the collaboration between the consortium and industry in the design of the trial will lead to an optimized study protocol. Lastly, analysis of the samples will enable exploratory biomarker research to identify new, non-invasive, biomarkers and potential companion diagnostics.
Collaborator Contribution Research collaboration, knowledge transfer and data sharing
Impact Genentech are providing the study drugs (tocilizumab and rituximab), and will provide expertise to help design the study and study protocol and will take part in analysis of samples (including serum, whole blood RNA and Synovial biopsy RNA) that could lead to potential companion diagnostics.
Start Year 2014
 
Description IMID-BIO-UK, Manchester 
Organisation Queen Mary University of London
Department William Harvey Research Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution PROVISION OF DATA AND BIOBANKED SAMPLES FROM RA-MAP
Collaborator Contribution PROVISION OF DATA AND BIOBANKED SAMPLES FROM MATURA, UK-PBC, Primary Sjogren's Syndrome registry
Impact TBD
Start Year 2018
 
Description IMID-BIO-UK, Manchester 
Organisation University of Cambridge
Department School of Clinical Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution PROVISION OF DATA AND BIOBANKED SAMPLES FROM RA-MAP
Collaborator Contribution PROVISION OF DATA AND BIOBANKED SAMPLES FROM MATURA, UK-PBC, Primary Sjogren's Syndrome registry
Impact TBD
Start Year 2018
 
Description IMID-BIO-UK, Manchester 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution PROVISION OF DATA AND BIOBANKED SAMPLES FROM RA-MAP
Collaborator Contribution PROVISION OF DATA AND BIOBANKED SAMPLES FROM MATURA, UK-PBC, Primary Sjogren's Syndrome registry
Impact TBD
Start Year 2018
 
Description IMID-BIO-UK, Manchester 
Organisation University of Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution PROVISION OF DATA AND BIOBANKED SAMPLES FROM RA-MAP
Collaborator Contribution PROVISION OF DATA AND BIOBANKED SAMPLES FROM MATURA, UK-PBC, Primary Sjogren's Syndrome registry
Impact TBD
Start Year 2018
 
Description Janssen 
Organisation Janssen Research & Development
Country Global 
Sector Private 
PI Contribution The main objective of this collaboration is for both industry and academic parties to engage in order to: 1. Develop a more accurate understanding of the mechanisms driving RA to inform clinically relevant developments of diagnostic algorithms and stratify patients to the most appropriate therapy. 2. Join the MATURA Research/Discovery Programme by contributing: a) expertise in analysis of RA genetic and genomic datasets b) access to replication cohorts for independent validation of primary results 3. Develop a companion diagnostic, based on the emerging of few cellular / molecular biomarkers that could be encompassed in a relatively simple test. 4. Potentially capitalise on the MATURA Consortium infrastructure to develop novel compounds which would benefit from disease tissue target validation.
Collaborator Contribution The main objective of this collaboration is for both industry and academic parties to engage in order to: 1. Develop a more accurate understanding of the mechanisms driving RA to inform clinically relevant developments of diagnostic algorithms and stratify patients to the most appropriate therapy. 2. Join the MATURA Research/Discovery Programme by contributing: a) expertise in analysis of RA genetic and genomic datasets b) access to replication cohorts for independent validation of primary results 3. Develop a companion diagnostic, based on the emerging of few cellular / molecular biomarkers that could be encompassed in a relatively simple test. 4. Potentially capitalise on the MATURA Consortium infrastructure to develop novel compounds which would benefit from disease tissue target validation.
Impact Janssen have already provided expertise and will potentially provide prior data to support specific hypothesis testing in MATURA. They have agreed access to unique patient populations for replication and validation of results from MATURA. They have also contributed knowledge and expertise in informatics and use of the TranSMART knowledge Management Platform.
Start Year 2014
 
Description MATURA Consortium 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution The collaboration is led and coordinated by Professor Pitzalis in London and Prof Barton in Manchester. There are 2 Work Streams. QMUL lead and contribute to WS1. WS1 will analyse synovial markers in the PEAC dataset (http://www.peac-mrc.mds.qmul.ac.uk) and run the prospective randomised clinical trial, STRAP, to test the hypothesis that discrete cellular and molecular signatures in the synovial tissue (pathotypes) can be utilized to predict the response to existing biological therapies. We will evaluate whether stratification of patients according to their synovial B cell infiltrate (poor or rich phenotypes) will better define response rates. We hypothesise that the Tocilizumab and Etanercept are superior to Rituximab in B-cell-poor patients. The ultimate aim is to provide a tailored approach to treatment decisions in patients at this stage of their disease, in order to maximise their potential response to therapy Work Stream 2 - has already collected blood samples and clinical information from large groups of patients treated with each of the 4 drugs we are focussing on (data on 3,000 anti-TNF, 1500 MTX 800 RTX and 200 TOC treated patients). We have followed these patients up from them starting the drug to 12 months later and, along the way, have collected blood samples, clinical information and data about the effectiveness and/or side effects of the drugs. This provides a wonderful starting point to test genetic variants, proteins and other molecules to find a set of biomarkers that together can be used to select the treatment most likely to work.
Collaborator Contribution All partners contribute to Project Steering Group meetings (quarterly) and the annual scientific meeting. WS1 partners are actively recruiting patients to the STRAP trial. WS2 partners are providing clinical samples, data and are involved in the analysis.
Impact Work ongoing
Start Year 2014
 
Description MATURA Consortium 
Organisation University College London
Department Division of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution The collaboration is led and coordinated by Professor Pitzalis in London and Prof Barton in Manchester. There are 2 Work Streams. QMUL lead and contribute to WS1. WS1 will analyse synovial markers in the PEAC dataset (http://www.peac-mrc.mds.qmul.ac.uk) and run the prospective randomised clinical trial, STRAP, to test the hypothesis that discrete cellular and molecular signatures in the synovial tissue (pathotypes) can be utilized to predict the response to existing biological therapies. We will evaluate whether stratification of patients according to their synovial B cell infiltrate (poor or rich phenotypes) will better define response rates. We hypothesise that the Tocilizumab and Etanercept are superior to Rituximab in B-cell-poor patients. The ultimate aim is to provide a tailored approach to treatment decisions in patients at this stage of their disease, in order to maximise their potential response to therapy Work Stream 2 - has already collected blood samples and clinical information from large groups of patients treated with each of the 4 drugs we are focussing on (data on 3,000 anti-TNF, 1500 MTX 800 RTX and 200 TOC treated patients). We have followed these patients up from them starting the drug to 12 months later and, along the way, have collected blood samples, clinical information and data about the effectiveness and/or side effects of the drugs. This provides a wonderful starting point to test genetic variants, proteins and other molecules to find a set of biomarkers that together can be used to select the treatment most likely to work.
Collaborator Contribution All partners contribute to Project Steering Group meetings (quarterly) and the annual scientific meeting. WS1 partners are actively recruiting patients to the STRAP trial. WS2 partners are providing clinical samples, data and are involved in the analysis.
Impact Work ongoing
Start Year 2014
 
Description MATURA Consortium 
Organisation University of Birmingham
Country United Kingdom 
Sector Academic/University 
PI Contribution The collaboration is led and coordinated by Professor Pitzalis in London and Prof Barton in Manchester. There are 2 Work Streams. QMUL lead and contribute to WS1. WS1 will analyse synovial markers in the PEAC dataset (http://www.peac-mrc.mds.qmul.ac.uk) and run the prospective randomised clinical trial, STRAP, to test the hypothesis that discrete cellular and molecular signatures in the synovial tissue (pathotypes) can be utilized to predict the response to existing biological therapies. We will evaluate whether stratification of patients according to their synovial B cell infiltrate (poor or rich phenotypes) will better define response rates. We hypothesise that the Tocilizumab and Etanercept are superior to Rituximab in B-cell-poor patients. The ultimate aim is to provide a tailored approach to treatment decisions in patients at this stage of their disease, in order to maximise their potential response to therapy Work Stream 2 - has already collected blood samples and clinical information from large groups of patients treated with each of the 4 drugs we are focussing on (data on 3,000 anti-TNF, 1500 MTX 800 RTX and 200 TOC treated patients). We have followed these patients up from them starting the drug to 12 months later and, along the way, have collected blood samples, clinical information and data about the effectiveness and/or side effects of the drugs. This provides a wonderful starting point to test genetic variants, proteins and other molecules to find a set of biomarkers that together can be used to select the treatment most likely to work.
Collaborator Contribution All partners contribute to Project Steering Group meetings (quarterly) and the annual scientific meeting. WS1 partners are actively recruiting patients to the STRAP trial. WS2 partners are providing clinical samples, data and are involved in the analysis.
Impact Work ongoing
Start Year 2014
 
Description MATURA Consortium 
Organisation University of Birmingham
Country United Kingdom 
Sector Academic/University 
PI Contribution The collaboration is led and coordinated by Professor Pitzalis in London and Prof Barton in Manchester. There are 2 Work Streams. QMUL lead and contribute to WS1. WS1 will analyse synovial markers in the PEAC dataset (http://www.peac-mrc.mds.qmul.ac.uk) and run the prospective randomised clinical trial, STRAP, to test the hypothesis that discrete cellular and molecular signatures in the synovial tissue (pathotypes) can be utilized to predict the response to existing biological therapies. We will evaluate whether stratification of patients according to their synovial B cell infiltrate (poor or rich phenotypes) will better define response rates. We hypothesise that the Tocilizumab and Etanercept are superior to Rituximab in B-cell-poor patients. The ultimate aim is to provide a tailored approach to treatment decisions in patients at this stage of their disease, in order to maximise their potential response to therapy Work Stream 2 - has already collected blood samples and clinical information from large groups of patients treated with each of the 4 drugs we are focussing on (data on 3,000 anti-TNF, 1500 MTX 800 RTX and 200 TOC treated patients). We have followed these patients up from them starting the drug to 12 months later and, along the way, have collected blood samples, clinical information and data about the effectiveness and/or side effects of the drugs. This provides a wonderful starting point to test genetic variants, proteins and other molecules to find a set of biomarkers that together can be used to select the treatment most likely to work.
Collaborator Contribution All partners contribute to Project Steering Group meetings (quarterly) and the annual scientific meeting. WS1 partners are actively recruiting patients to the STRAP trial. WS2 partners are providing clinical samples, data and are involved in the analysis.
Impact Work ongoing
Start Year 2014
 
Description MATURA Consortium 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution The collaboration is led and coordinated by Professor Pitzalis in London and Prof Barton in Manchester. There are 2 Work Streams. QMUL lead and contribute to WS1. WS1 will analyse synovial markers in the PEAC dataset (http://www.peac-mrc.mds.qmul.ac.uk) and run the prospective randomised clinical trial, STRAP, to test the hypothesis that discrete cellular and molecular signatures in the synovial tissue (pathotypes) can be utilized to predict the response to existing biological therapies. We will evaluate whether stratification of patients according to their synovial B cell infiltrate (poor or rich phenotypes) will better define response rates. We hypothesise that the Tocilizumab and Etanercept are superior to Rituximab in B-cell-poor patients. The ultimate aim is to provide a tailored approach to treatment decisions in patients at this stage of their disease, in order to maximise their potential response to therapy Work Stream 2 - has already collected blood samples and clinical information from large groups of patients treated with each of the 4 drugs we are focussing on (data on 3,000 anti-TNF, 1500 MTX 800 RTX and 200 TOC treated patients). We have followed these patients up from them starting the drug to 12 months later and, along the way, have collected blood samples, clinical information and data about the effectiveness and/or side effects of the drugs. This provides a wonderful starting point to test genetic variants, proteins and other molecules to find a set of biomarkers that together can be used to select the treatment most likely to work.
Collaborator Contribution All partners contribute to Project Steering Group meetings (quarterly) and the annual scientific meeting. WS1 partners are actively recruiting patients to the STRAP trial. WS2 partners are providing clinical samples, data and are involved in the analysis.
Impact Work ongoing
Start Year 2014
 
Description MATURA Consortium 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution The collaboration is led and coordinated by Professor Pitzalis in London and Prof Barton in Manchester. There are 2 Work Streams. QMUL lead and contribute to WS1. WS1 will analyse synovial markers in the PEAC dataset (http://www.peac-mrc.mds.qmul.ac.uk) and run the prospective randomised clinical trial, STRAP, to test the hypothesis that discrete cellular and molecular signatures in the synovial tissue (pathotypes) can be utilized to predict the response to existing biological therapies. We will evaluate whether stratification of patients according to their synovial B cell infiltrate (poor or rich phenotypes) will better define response rates. We hypothesise that the Tocilizumab and Etanercept are superior to Rituximab in B-cell-poor patients. The ultimate aim is to provide a tailored approach to treatment decisions in patients at this stage of their disease, in order to maximise their potential response to therapy Work Stream 2 - has already collected blood samples and clinical information from large groups of patients treated with each of the 4 drugs we are focussing on (data on 3,000 anti-TNF, 1500 MTX 800 RTX and 200 TOC treated patients). We have followed these patients up from them starting the drug to 12 months later and, along the way, have collected blood samples, clinical information and data about the effectiveness and/or side effects of the drugs. This provides a wonderful starting point to test genetic variants, proteins and other molecules to find a set of biomarkers that together can be used to select the treatment most likely to work.
Collaborator Contribution All partners contribute to Project Steering Group meetings (quarterly) and the annual scientific meeting. WS1 partners are actively recruiting patients to the STRAP trial. WS2 partners are providing clinical samples, data and are involved in the analysis.
Impact Work ongoing
Start Year 2014
 
Description MATURA Consortium 
Organisation University of Hertfordshire
Country United Kingdom 
Sector Academic/University 
PI Contribution The collaboration is led and coordinated by Professor Pitzalis in London and Prof Barton in Manchester. There are 2 Work Streams. QMUL lead and contribute to WS1. WS1 will analyse synovial markers in the PEAC dataset (http://www.peac-mrc.mds.qmul.ac.uk) and run the prospective randomised clinical trial, STRAP, to test the hypothesis that discrete cellular and molecular signatures in the synovial tissue (pathotypes) can be utilized to predict the response to existing biological therapies. We will evaluate whether stratification of patients according to their synovial B cell infiltrate (poor or rich phenotypes) will better define response rates. We hypothesise that the Tocilizumab and Etanercept are superior to Rituximab in B-cell-poor patients. The ultimate aim is to provide a tailored approach to treatment decisions in patients at this stage of their disease, in order to maximise their potential response to therapy Work Stream 2 - has already collected blood samples and clinical information from large groups of patients treated with each of the 4 drugs we are focussing on (data on 3,000 anti-TNF, 1500 MTX 800 RTX and 200 TOC treated patients). We have followed these patients up from them starting the drug to 12 months later and, along the way, have collected blood samples, clinical information and data about the effectiveness and/or side effects of the drugs. This provides a wonderful starting point to test genetic variants, proteins and other molecules to find a set of biomarkers that together can be used to select the treatment most likely to work.
Collaborator Contribution All partners contribute to Project Steering Group meetings (quarterly) and the annual scientific meeting. WS1 partners are actively recruiting patients to the STRAP trial. WS2 partners are providing clinical samples, data and are involved in the analysis.
Impact Work ongoing
Start Year 2014
 
Description MATURA Consortium 
Organisation University of Leeds
Country United Kingdom 
Sector Academic/University 
PI Contribution The collaboration is led and coordinated by Professor Pitzalis in London and Prof Barton in Manchester. There are 2 Work Streams. QMUL lead and contribute to WS1. WS1 will analyse synovial markers in the PEAC dataset (http://www.peac-mrc.mds.qmul.ac.uk) and run the prospective randomised clinical trial, STRAP, to test the hypothesis that discrete cellular and molecular signatures in the synovial tissue (pathotypes) can be utilized to predict the response to existing biological therapies. We will evaluate whether stratification of patients according to their synovial B cell infiltrate (poor or rich phenotypes) will better define response rates. We hypothesise that the Tocilizumab and Etanercept are superior to Rituximab in B-cell-poor patients. The ultimate aim is to provide a tailored approach to treatment decisions in patients at this stage of their disease, in order to maximise their potential response to therapy Work Stream 2 - has already collected blood samples and clinical information from large groups of patients treated with each of the 4 drugs we are focussing on (data on 3,000 anti-TNF, 1500 MTX 800 RTX and 200 TOC treated patients). We have followed these patients up from them starting the drug to 12 months later and, along the way, have collected blood samples, clinical information and data about the effectiveness and/or side effects of the drugs. This provides a wonderful starting point to test genetic variants, proteins and other molecules to find a set of biomarkers that together can be used to select the treatment most likely to work.
Collaborator Contribution All partners contribute to Project Steering Group meetings (quarterly) and the annual scientific meeting. WS1 partners are actively recruiting patients to the STRAP trial. WS2 partners are providing clinical samples, data and are involved in the analysis.
Impact Work ongoing
Start Year 2014
 
Description MATURA Consortium 
Organisation University of Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution The collaboration is led and coordinated by Professor Pitzalis in London and Prof Barton in Manchester. There are 2 Work Streams. QMUL lead and contribute to WS1. WS1 will analyse synovial markers in the PEAC dataset (http://www.peac-mrc.mds.qmul.ac.uk) and run the prospective randomised clinical trial, STRAP, to test the hypothesis that discrete cellular and molecular signatures in the synovial tissue (pathotypes) can be utilized to predict the response to existing biological therapies. We will evaluate whether stratification of patients according to their synovial B cell infiltrate (poor or rich phenotypes) will better define response rates. We hypothesise that the Tocilizumab and Etanercept are superior to Rituximab in B-cell-poor patients. The ultimate aim is to provide a tailored approach to treatment decisions in patients at this stage of their disease, in order to maximise their potential response to therapy Work Stream 2 - has already collected blood samples and clinical information from large groups of patients treated with each of the 4 drugs we are focussing on (data on 3,000 anti-TNF, 1500 MTX 800 RTX and 200 TOC treated patients). We have followed these patients up from them starting the drug to 12 months later and, along the way, have collected blood samples, clinical information and data about the effectiveness and/or side effects of the drugs. This provides a wonderful starting point to test genetic variants, proteins and other molecules to find a set of biomarkers that together can be used to select the treatment most likely to work.
Collaborator Contribution All partners contribute to Project Steering Group meetings (quarterly) and the annual scientific meeting. WS1 partners are actively recruiting patients to the STRAP trial. WS2 partners are providing clinical samples, data and are involved in the analysis.
Impact Work ongoing
Start Year 2014
 
Description MATURA Consortium 
Organisation University of Newcastle
Country Australia 
Sector Academic/University 
PI Contribution The collaboration is led and coordinated by Professor Pitzalis in London and Prof Barton in Manchester. There are 2 Work Streams. QMUL lead and contribute to WS1. WS1 will analyse synovial markers in the PEAC dataset (http://www.peac-mrc.mds.qmul.ac.uk) and run the prospective randomised clinical trial, STRAP, to test the hypothesis that discrete cellular and molecular signatures in the synovial tissue (pathotypes) can be utilized to predict the response to existing biological therapies. We will evaluate whether stratification of patients according to their synovial B cell infiltrate (poor or rich phenotypes) will better define response rates. We hypothesise that the Tocilizumab and Etanercept are superior to Rituximab in B-cell-poor patients. The ultimate aim is to provide a tailored approach to treatment decisions in patients at this stage of their disease, in order to maximise their potential response to therapy Work Stream 2 - has already collected blood samples and clinical information from large groups of patients treated with each of the 4 drugs we are focussing on (data on 3,000 anti-TNF, 1500 MTX 800 RTX and 200 TOC treated patients). We have followed these patients up from them starting the drug to 12 months later and, along the way, have collected blood samples, clinical information and data about the effectiveness and/or side effects of the drugs. This provides a wonderful starting point to test genetic variants, proteins and other molecules to find a set of biomarkers that together can be used to select the treatment most likely to work.
Collaborator Contribution All partners contribute to Project Steering Group meetings (quarterly) and the annual scientific meeting. WS1 partners are actively recruiting patients to the STRAP trial. WS2 partners are providing clinical samples, data and are involved in the analysis.
Impact Work ongoing
Start Year 2014
 
Description MATURA Consortium 
Organisation University of Oxford
Department Botnar Research Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution The collaboration is led and coordinated by Professor Pitzalis in London and Prof Barton in Manchester. There are 2 Work Streams. QMUL lead and contribute to WS1. WS1 will analyse synovial markers in the PEAC dataset (http://www.peac-mrc.mds.qmul.ac.uk) and run the prospective randomised clinical trial, STRAP, to test the hypothesis that discrete cellular and molecular signatures in the synovial tissue (pathotypes) can be utilized to predict the response to existing biological therapies. We will evaluate whether stratification of patients according to their synovial B cell infiltrate (poor or rich phenotypes) will better define response rates. We hypothesise that the Tocilizumab and Etanercept are superior to Rituximab in B-cell-poor patients. The ultimate aim is to provide a tailored approach to treatment decisions in patients at this stage of their disease, in order to maximise their potential response to therapy Work Stream 2 - has already collected blood samples and clinical information from large groups of patients treated with each of the 4 drugs we are focussing on (data on 3,000 anti-TNF, 1500 MTX 800 RTX and 200 TOC treated patients). We have followed these patients up from them starting the drug to 12 months later and, along the way, have collected blood samples, clinical information and data about the effectiveness and/or side effects of the drugs. This provides a wonderful starting point to test genetic variants, proteins and other molecules to find a set of biomarkers that together can be used to select the treatment most likely to work.
Collaborator Contribution All partners contribute to Project Steering Group meetings (quarterly) and the annual scientific meeting. WS1 partners are actively recruiting patients to the STRAP trial. WS2 partners are providing clinical samples, data and are involved in the analysis.
Impact Work ongoing
Start Year 2014
 
Description MATURA consortium 
Organisation Cardiff University
Country United Kingdom 
Sector Academic/University 
PI Contribution recruitment to the STRAP trial proteomic analyses
Collaborator Contribution The overarching mission of the MATURA Consortium is to improve patient care in rheumatoid arthritis (RA) by rationalising therapy decisions through the use of a stratified medicines approach. Background: RA provides the ideal setting for the introduction of a stratified medicine approach because, first, the treatment is standardised in England through National Institute of Health and Clinical Excellence (NICE) guidance such that methotrexate (MTX) is the first choice disease modifying anti-rheumatic drug (DMARD); patients who fail to respond to MTX and at least one other DMARD are eligible for biologic TNF pathway blocking drugs (anti- TNFs) or, more recently IL6 pathway blocking drugs, tocilizumab (TOC), and those who fail to respond to anti-TNF can then be switched to the biologic B-cell depleting therapy, rituximab (RTX). Second, it is well established that there is a significant non - response rate to each drug (MTX (45% by 2 years), anti-TNF (25% by 6 months) and RTX (40% by 6 months). Third, the biologic drugs (anti-TNF, TOC and RTX) are expensive and all 4 drugs are associated with serious adverse events; hence, identifying those patients least likely to respond would improve the cost-benefit analysis. Finally, introduction of early, effective therapy has consistently been shown to improve long-term outcomes including joint damage, disability and employment. Aim: To identify treatment response predictors which will allow the allocation of patients to strata defined by the therapy they are most likely to respond to, early in the disease process. Methods: Two parallel workstrands (WS) will investigate synovial tissue (WS.1) and peripheral blood (WS.2) to identify biomarkers of response. Thus, in WS.1 we shall search for tissue-driven biomarkers and blood correlates in the largest synovial tissue biobank of this type (2 time points 0 & 6 months biopsy) in the world & clinical datasets (over 200 patients immediately available). In addition, in a prospective randomised clinical trial (adaptive design) we will test the hypothesis that discrete cellular and molecular signatures in the synovial tissue ("pathotypes") will enrich for response to existing biologic therapies. In WS.2, we will take advantage of the large observational cohorts of patient samples either already collected or which could be collected for minimal cost to undertake a comprehensive analysis to identify genetic, genomic, transcriptomic, proteomic or, more likely, a combination of these factors that will reliably identify responders/non-responders to each of the drugs. These collections include biological samples from over 3,000 anti-TNF-, 1,500 MTX-, 1,200 RTX- and 200 TOC-treated subjects. The two WSs are fully integrated through "multi-omic" approaches that constitute cross-cutting themes (CTs) that will converge in a large analytical and modelling package driven by experts in Bioinformatics and Statistics and allow preliminary health economic assessments of identified biomarkers. Finally, in collaboration with our Industry partners we have drawn up plans to commercialize potential diagnostics for patient benefit and wealth generation. Outcome: By the end of the study, we will have identified biomarkers of response for four of the most commonly used drugs in the treatment of RA. The study design allows a comprehensive and cohesive assault on the problem of identifying, which patients will respond best to which treatments in RA and has the potential for enormous clinical and economic impact.
Impact Medicine statistics bioinformatics multiple industry partners
Start Year 2014
 
Description MATURA consortium 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution recruitment to the STRAP trial proteomic analyses
Collaborator Contribution The overarching mission of the MATURA Consortium is to improve patient care in rheumatoid arthritis (RA) by rationalising therapy decisions through the use of a stratified medicines approach. Background: RA provides the ideal setting for the introduction of a stratified medicine approach because, first, the treatment is standardised in England through National Institute of Health and Clinical Excellence (NICE) guidance such that methotrexate (MTX) is the first choice disease modifying anti-rheumatic drug (DMARD); patients who fail to respond to MTX and at least one other DMARD are eligible for biologic TNF pathway blocking drugs (anti- TNFs) or, more recently IL6 pathway blocking drugs, tocilizumab (TOC), and those who fail to respond to anti-TNF can then be switched to the biologic B-cell depleting therapy, rituximab (RTX). Second, it is well established that there is a significant non - response rate to each drug (MTX (45% by 2 years), anti-TNF (25% by 6 months) and RTX (40% by 6 months). Third, the biologic drugs (anti-TNF, TOC and RTX) are expensive and all 4 drugs are associated with serious adverse events; hence, identifying those patients least likely to respond would improve the cost-benefit analysis. Finally, introduction of early, effective therapy has consistently been shown to improve long-term outcomes including joint damage, disability and employment. Aim: To identify treatment response predictors which will allow the allocation of patients to strata defined by the therapy they are most likely to respond to, early in the disease process. Methods: Two parallel workstrands (WS) will investigate synovial tissue (WS.1) and peripheral blood (WS.2) to identify biomarkers of response. Thus, in WS.1 we shall search for tissue-driven biomarkers and blood correlates in the largest synovial tissue biobank of this type (2 time points 0 & 6 months biopsy) in the world & clinical datasets (over 200 patients immediately available). In addition, in a prospective randomised clinical trial (adaptive design) we will test the hypothesis that discrete cellular and molecular signatures in the synovial tissue ("pathotypes") will enrich for response to existing biologic therapies. In WS.2, we will take advantage of the large observational cohorts of patient samples either already collected or which could be collected for minimal cost to undertake a comprehensive analysis to identify genetic, genomic, transcriptomic, proteomic or, more likely, a combination of these factors that will reliably identify responders/non-responders to each of the drugs. These collections include biological samples from over 3,000 anti-TNF-, 1,500 MTX-, 1,200 RTX- and 200 TOC-treated subjects. The two WSs are fully integrated through "multi-omic" approaches that constitute cross-cutting themes (CTs) that will converge in a large analytical and modelling package driven by experts in Bioinformatics and Statistics and allow preliminary health economic assessments of identified biomarkers. Finally, in collaboration with our Industry partners we have drawn up plans to commercialize potential diagnostics for patient benefit and wealth generation. Outcome: By the end of the study, we will have identified biomarkers of response for four of the most commonly used drugs in the treatment of RA. The study design allows a comprehensive and cohesive assault on the problem of identifying, which patients will respond best to which treatments in RA and has the potential for enormous clinical and economic impact.
Impact Medicine statistics bioinformatics multiple industry partners
Start Year 2014
 
Description MATURA consortium 
Organisation Queen Mary University of London
Department William Harvey Research Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution recruitment to the STRAP trial proteomic analyses
Collaborator Contribution The overarching mission of the MATURA Consortium is to improve patient care in rheumatoid arthritis (RA) by rationalising therapy decisions through the use of a stratified medicines approach. Background: RA provides the ideal setting for the introduction of a stratified medicine approach because, first, the treatment is standardised in England through National Institute of Health and Clinical Excellence (NICE) guidance such that methotrexate (MTX) is the first choice disease modifying anti-rheumatic drug (DMARD); patients who fail to respond to MTX and at least one other DMARD are eligible for biologic TNF pathway blocking drugs (anti- TNFs) or, more recently IL6 pathway blocking drugs, tocilizumab (TOC), and those who fail to respond to anti-TNF can then be switched to the biologic B-cell depleting therapy, rituximab (RTX). Second, it is well established that there is a significant non - response rate to each drug (MTX (45% by 2 years), anti-TNF (25% by 6 months) and RTX (40% by 6 months). Third, the biologic drugs (anti-TNF, TOC and RTX) are expensive and all 4 drugs are associated with serious adverse events; hence, identifying those patients least likely to respond would improve the cost-benefit analysis. Finally, introduction of early, effective therapy has consistently been shown to improve long-term outcomes including joint damage, disability and employment. Aim: To identify treatment response predictors which will allow the allocation of patients to strata defined by the therapy they are most likely to respond to, early in the disease process. Methods: Two parallel workstrands (WS) will investigate synovial tissue (WS.1) and peripheral blood (WS.2) to identify biomarkers of response. Thus, in WS.1 we shall search for tissue-driven biomarkers and blood correlates in the largest synovial tissue biobank of this type (2 time points 0 & 6 months biopsy) in the world & clinical datasets (over 200 patients immediately available). In addition, in a prospective randomised clinical trial (adaptive design) we will test the hypothesis that discrete cellular and molecular signatures in the synovial tissue ("pathotypes") will enrich for response to existing biologic therapies. In WS.2, we will take advantage of the large observational cohorts of patient samples either already collected or which could be collected for minimal cost to undertake a comprehensive analysis to identify genetic, genomic, transcriptomic, proteomic or, more likely, a combination of these factors that will reliably identify responders/non-responders to each of the drugs. These collections include biological samples from over 3,000 anti-TNF-, 1,500 MTX-, 1,200 RTX- and 200 TOC-treated subjects. The two WSs are fully integrated through "multi-omic" approaches that constitute cross-cutting themes (CTs) that will converge in a large analytical and modelling package driven by experts in Bioinformatics and Statistics and allow preliminary health economic assessments of identified biomarkers. Finally, in collaboration with our Industry partners we have drawn up plans to commercialize potential diagnostics for patient benefit and wealth generation. Outcome: By the end of the study, we will have identified biomarkers of response for four of the most commonly used drugs in the treatment of RA. The study design allows a comprehensive and cohesive assault on the problem of identifying, which patients will respond best to which treatments in RA and has the potential for enormous clinical and economic impact.
Impact Medicine statistics bioinformatics multiple industry partners
Start Year 2014
 
Description MATURA consortium 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution recruitment to the STRAP trial proteomic analyses
Collaborator Contribution The overarching mission of the MATURA Consortium is to improve patient care in rheumatoid arthritis (RA) by rationalising therapy decisions through the use of a stratified medicines approach. Background: RA provides the ideal setting for the introduction of a stratified medicine approach because, first, the treatment is standardised in England through National Institute of Health and Clinical Excellence (NICE) guidance such that methotrexate (MTX) is the first choice disease modifying anti-rheumatic drug (DMARD); patients who fail to respond to MTX and at least one other DMARD are eligible for biologic TNF pathway blocking drugs (anti- TNFs) or, more recently IL6 pathway blocking drugs, tocilizumab (TOC), and those who fail to respond to anti-TNF can then be switched to the biologic B-cell depleting therapy, rituximab (RTX). Second, it is well established that there is a significant non - response rate to each drug (MTX (45% by 2 years), anti-TNF (25% by 6 months) and RTX (40% by 6 months). Third, the biologic drugs (anti-TNF, TOC and RTX) are expensive and all 4 drugs are associated with serious adverse events; hence, identifying those patients least likely to respond would improve the cost-benefit analysis. Finally, introduction of early, effective therapy has consistently been shown to improve long-term outcomes including joint damage, disability and employment. Aim: To identify treatment response predictors which will allow the allocation of patients to strata defined by the therapy they are most likely to respond to, early in the disease process. Methods: Two parallel workstrands (WS) will investigate synovial tissue (WS.1) and peripheral blood (WS.2) to identify biomarkers of response. Thus, in WS.1 we shall search for tissue-driven biomarkers and blood correlates in the largest synovial tissue biobank of this type (2 time points 0 & 6 months biopsy) in the world & clinical datasets (over 200 patients immediately available). In addition, in a prospective randomised clinical trial (adaptive design) we will test the hypothesis that discrete cellular and molecular signatures in the synovial tissue ("pathotypes") will enrich for response to existing biologic therapies. In WS.2, we will take advantage of the large observational cohorts of patient samples either already collected or which could be collected for minimal cost to undertake a comprehensive analysis to identify genetic, genomic, transcriptomic, proteomic or, more likely, a combination of these factors that will reliably identify responders/non-responders to each of the drugs. These collections include biological samples from over 3,000 anti-TNF-, 1,500 MTX-, 1,200 RTX- and 200 TOC-treated subjects. The two WSs are fully integrated through "multi-omic" approaches that constitute cross-cutting themes (CTs) that will converge in a large analytical and modelling package driven by experts in Bioinformatics and Statistics and allow preliminary health economic assessments of identified biomarkers. Finally, in collaboration with our Industry partners we have drawn up plans to commercialize potential diagnostics for patient benefit and wealth generation. Outcome: By the end of the study, we will have identified biomarkers of response for four of the most commonly used drugs in the treatment of RA. The study design allows a comprehensive and cohesive assault on the problem of identifying, which patients will respond best to which treatments in RA and has the potential for enormous clinical and economic impact.
Impact Medicine statistics bioinformatics multiple industry partners
Start Year 2014
 
Description MATURA consortium 
Organisation University of Birmingham
Country United Kingdom 
Sector Academic/University 
PI Contribution recruitment to the STRAP trial proteomic analyses
Collaborator Contribution The overarching mission of the MATURA Consortium is to improve patient care in rheumatoid arthritis (RA) by rationalising therapy decisions through the use of a stratified medicines approach. Background: RA provides the ideal setting for the introduction of a stratified medicine approach because, first, the treatment is standardised in England through National Institute of Health and Clinical Excellence (NICE) guidance such that methotrexate (MTX) is the first choice disease modifying anti-rheumatic drug (DMARD); patients who fail to respond to MTX and at least one other DMARD are eligible for biologic TNF pathway blocking drugs (anti- TNFs) or, more recently IL6 pathway blocking drugs, tocilizumab (TOC), and those who fail to respond to anti-TNF can then be switched to the biologic B-cell depleting therapy, rituximab (RTX). Second, it is well established that there is a significant non - response rate to each drug (MTX (45% by 2 years), anti-TNF (25% by 6 months) and RTX (40% by 6 months). Third, the biologic drugs (anti-TNF, TOC and RTX) are expensive and all 4 drugs are associated with serious adverse events; hence, identifying those patients least likely to respond would improve the cost-benefit analysis. Finally, introduction of early, effective therapy has consistently been shown to improve long-term outcomes including joint damage, disability and employment. Aim: To identify treatment response predictors which will allow the allocation of patients to strata defined by the therapy they are most likely to respond to, early in the disease process. Methods: Two parallel workstrands (WS) will investigate synovial tissue (WS.1) and peripheral blood (WS.2) to identify biomarkers of response. Thus, in WS.1 we shall search for tissue-driven biomarkers and blood correlates in the largest synovial tissue biobank of this type (2 time points 0 & 6 months biopsy) in the world & clinical datasets (over 200 patients immediately available). In addition, in a prospective randomised clinical trial (adaptive design) we will test the hypothesis that discrete cellular and molecular signatures in the synovial tissue ("pathotypes") will enrich for response to existing biologic therapies. In WS.2, we will take advantage of the large observational cohorts of patient samples either already collected or which could be collected for minimal cost to undertake a comprehensive analysis to identify genetic, genomic, transcriptomic, proteomic or, more likely, a combination of these factors that will reliably identify responders/non-responders to each of the drugs. These collections include biological samples from over 3,000 anti-TNF-, 1,500 MTX-, 1,200 RTX- and 200 TOC-treated subjects. The two WSs are fully integrated through "multi-omic" approaches that constitute cross-cutting themes (CTs) that will converge in a large analytical and modelling package driven by experts in Bioinformatics and Statistics and allow preliminary health economic assessments of identified biomarkers. Finally, in collaboration with our Industry partners we have drawn up plans to commercialize potential diagnostics for patient benefit and wealth generation. Outcome: By the end of the study, we will have identified biomarkers of response for four of the most commonly used drugs in the treatment of RA. The study design allows a comprehensive and cohesive assault on the problem of identifying, which patients will respond best to which treatments in RA and has the potential for enormous clinical and economic impact.
Impact Medicine statistics bioinformatics multiple industry partners
Start Year 2014
 
Description MATURA consortium 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution recruitment to the STRAP trial proteomic analyses
Collaborator Contribution The overarching mission of the MATURA Consortium is to improve patient care in rheumatoid arthritis (RA) by rationalising therapy decisions through the use of a stratified medicines approach. Background: RA provides the ideal setting for the introduction of a stratified medicine approach because, first, the treatment is standardised in England through National Institute of Health and Clinical Excellence (NICE) guidance such that methotrexate (MTX) is the first choice disease modifying anti-rheumatic drug (DMARD); patients who fail to respond to MTX and at least one other DMARD are eligible for biologic TNF pathway blocking drugs (anti- TNFs) or, more recently IL6 pathway blocking drugs, tocilizumab (TOC), and those who fail to respond to anti-TNF can then be switched to the biologic B-cell depleting therapy, rituximab (RTX). Second, it is well established that there is a significant non - response rate to each drug (MTX (45% by 2 years), anti-TNF (25% by 6 months) and RTX (40% by 6 months). Third, the biologic drugs (anti-TNF, TOC and RTX) are expensive and all 4 drugs are associated with serious adverse events; hence, identifying those patients least likely to respond would improve the cost-benefit analysis. Finally, introduction of early, effective therapy has consistently been shown to improve long-term outcomes including joint damage, disability and employment. Aim: To identify treatment response predictors which will allow the allocation of patients to strata defined by the therapy they are most likely to respond to, early in the disease process. Methods: Two parallel workstrands (WS) will investigate synovial tissue (WS.1) and peripheral blood (WS.2) to identify biomarkers of response. Thus, in WS.1 we shall search for tissue-driven biomarkers and blood correlates in the largest synovial tissue biobank of this type (2 time points 0 & 6 months biopsy) in the world & clinical datasets (over 200 patients immediately available). In addition, in a prospective randomised clinical trial (adaptive design) we will test the hypothesis that discrete cellular and molecular signatures in the synovial tissue ("pathotypes") will enrich for response to existing biologic therapies. In WS.2, we will take advantage of the large observational cohorts of patient samples either already collected or which could be collected for minimal cost to undertake a comprehensive analysis to identify genetic, genomic, transcriptomic, proteomic or, more likely, a combination of these factors that will reliably identify responders/non-responders to each of the drugs. These collections include biological samples from over 3,000 anti-TNF-, 1,500 MTX-, 1,200 RTX- and 200 TOC-treated subjects. The two WSs are fully integrated through "multi-omic" approaches that constitute cross-cutting themes (CTs) that will converge in a large analytical and modelling package driven by experts in Bioinformatics and Statistics and allow preliminary health economic assessments of identified biomarkers. Finally, in collaboration with our Industry partners we have drawn up plans to commercialize potential diagnostics for patient benefit and wealth generation. Outcome: By the end of the study, we will have identified biomarkers of response for four of the most commonly used drugs in the treatment of RA. The study design allows a comprehensive and cohesive assault on the problem of identifying, which patients will respond best to which treatments in RA and has the potential for enormous clinical and economic impact.
Impact Medicine statistics bioinformatics multiple industry partners
Start Year 2014
 
Description MATURA consortium 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution recruitment to the STRAP trial proteomic analyses
Collaborator Contribution The overarching mission of the MATURA Consortium is to improve patient care in rheumatoid arthritis (RA) by rationalising therapy decisions through the use of a stratified medicines approach. Background: RA provides the ideal setting for the introduction of a stratified medicine approach because, first, the treatment is standardised in England through National Institute of Health and Clinical Excellence (NICE) guidance such that methotrexate (MTX) is the first choice disease modifying anti-rheumatic drug (DMARD); patients who fail to respond to MTX and at least one other DMARD are eligible for biologic TNF pathway blocking drugs (anti- TNFs) or, more recently IL6 pathway blocking drugs, tocilizumab (TOC), and those who fail to respond to anti-TNF can then be switched to the biologic B-cell depleting therapy, rituximab (RTX). Second, it is well established that there is a significant non - response rate to each drug (MTX (45% by 2 years), anti-TNF (25% by 6 months) and RTX (40% by 6 months). Third, the biologic drugs (anti-TNF, TOC and RTX) are expensive and all 4 drugs are associated with serious adverse events; hence, identifying those patients least likely to respond would improve the cost-benefit analysis. Finally, introduction of early, effective therapy has consistently been shown to improve long-term outcomes including joint damage, disability and employment. Aim: To identify treatment response predictors which will allow the allocation of patients to strata defined by the therapy they are most likely to respond to, early in the disease process. Methods: Two parallel workstrands (WS) will investigate synovial tissue (WS.1) and peripheral blood (WS.2) to identify biomarkers of response. Thus, in WS.1 we shall search for tissue-driven biomarkers and blood correlates in the largest synovial tissue biobank of this type (2 time points 0 & 6 months biopsy) in the world & clinical datasets (over 200 patients immediately available). In addition, in a prospective randomised clinical trial (adaptive design) we will test the hypothesis that discrete cellular and molecular signatures in the synovial tissue ("pathotypes") will enrich for response to existing biologic therapies. In WS.2, we will take advantage of the large observational cohorts of patient samples either already collected or which could be collected for minimal cost to undertake a comprehensive analysis to identify genetic, genomic, transcriptomic, proteomic or, more likely, a combination of these factors that will reliably identify responders/non-responders to each of the drugs. These collections include biological samples from over 3,000 anti-TNF-, 1,500 MTX-, 1,200 RTX- and 200 TOC-treated subjects. The two WSs are fully integrated through "multi-omic" approaches that constitute cross-cutting themes (CTs) that will converge in a large analytical and modelling package driven by experts in Bioinformatics and Statistics and allow preliminary health economic assessments of identified biomarkers. Finally, in collaboration with our Industry partners we have drawn up plans to commercialize potential diagnostics for patient benefit and wealth generation. Outcome: By the end of the study, we will have identified biomarkers of response for four of the most commonly used drugs in the treatment of RA. The study design allows a comprehensive and cohesive assault on the problem of identifying, which patients will respond best to which treatments in RA and has the potential for enormous clinical and economic impact.
Impact Medicine statistics bioinformatics multiple industry partners
Start Year 2014
 
Description MATURA consortium 
Organisation University of Hertfordshire
Country United Kingdom 
Sector Academic/University 
PI Contribution recruitment to the STRAP trial proteomic analyses
Collaborator Contribution The overarching mission of the MATURA Consortium is to improve patient care in rheumatoid arthritis (RA) by rationalising therapy decisions through the use of a stratified medicines approach. Background: RA provides the ideal setting for the introduction of a stratified medicine approach because, first, the treatment is standardised in England through National Institute of Health and Clinical Excellence (NICE) guidance such that methotrexate (MTX) is the first choice disease modifying anti-rheumatic drug (DMARD); patients who fail to respond to MTX and at least one other DMARD are eligible for biologic TNF pathway blocking drugs (anti- TNFs) or, more recently IL6 pathway blocking drugs, tocilizumab (TOC), and those who fail to respond to anti-TNF can then be switched to the biologic B-cell depleting therapy, rituximab (RTX). Second, it is well established that there is a significant non - response rate to each drug (MTX (45% by 2 years), anti-TNF (25% by 6 months) and RTX (40% by 6 months). Third, the biologic drugs (anti-TNF, TOC and RTX) are expensive and all 4 drugs are associated with serious adverse events; hence, identifying those patients least likely to respond would improve the cost-benefit analysis. Finally, introduction of early, effective therapy has consistently been shown to improve long-term outcomes including joint damage, disability and employment. Aim: To identify treatment response predictors which will allow the allocation of patients to strata defined by the therapy they are most likely to respond to, early in the disease process. Methods: Two parallel workstrands (WS) will investigate synovial tissue (WS.1) and peripheral blood (WS.2) to identify biomarkers of response. Thus, in WS.1 we shall search for tissue-driven biomarkers and blood correlates in the largest synovial tissue biobank of this type (2 time points 0 & 6 months biopsy) in the world & clinical datasets (over 200 patients immediately available). In addition, in a prospective randomised clinical trial (adaptive design) we will test the hypothesis that discrete cellular and molecular signatures in the synovial tissue ("pathotypes") will enrich for response to existing biologic therapies. In WS.2, we will take advantage of the large observational cohorts of patient samples either already collected or which could be collected for minimal cost to undertake a comprehensive analysis to identify genetic, genomic, transcriptomic, proteomic or, more likely, a combination of these factors that will reliably identify responders/non-responders to each of the drugs. These collections include biological samples from over 3,000 anti-TNF-, 1,500 MTX-, 1,200 RTX- and 200 TOC-treated subjects. The two WSs are fully integrated through "multi-omic" approaches that constitute cross-cutting themes (CTs) that will converge in a large analytical and modelling package driven by experts in Bioinformatics and Statistics and allow preliminary health economic assessments of identified biomarkers. Finally, in collaboration with our Industry partners we have drawn up plans to commercialize potential diagnostics for patient benefit and wealth generation. Outcome: By the end of the study, we will have identified biomarkers of response for four of the most commonly used drugs in the treatment of RA. The study design allows a comprehensive and cohesive assault on the problem of identifying, which patients will respond best to which treatments in RA and has the potential for enormous clinical and economic impact.
Impact Medicine statistics bioinformatics multiple industry partners
Start Year 2014
 
Description MATURA consortium 
Organisation University of Leeds
Country United Kingdom 
Sector Academic/University 
PI Contribution recruitment to the STRAP trial proteomic analyses
Collaborator Contribution The overarching mission of the MATURA Consortium is to improve patient care in rheumatoid arthritis (RA) by rationalising therapy decisions through the use of a stratified medicines approach. Background: RA provides the ideal setting for the introduction of a stratified medicine approach because, first, the treatment is standardised in England through National Institute of Health and Clinical Excellence (NICE) guidance such that methotrexate (MTX) is the first choice disease modifying anti-rheumatic drug (DMARD); patients who fail to respond to MTX and at least one other DMARD are eligible for biologic TNF pathway blocking drugs (anti- TNFs) or, more recently IL6 pathway blocking drugs, tocilizumab (TOC), and those who fail to respond to anti-TNF can then be switched to the biologic B-cell depleting therapy, rituximab (RTX). Second, it is well established that there is a significant non - response rate to each drug (MTX (45% by 2 years), anti-TNF (25% by 6 months) and RTX (40% by 6 months). Third, the biologic drugs (anti-TNF, TOC and RTX) are expensive and all 4 drugs are associated with serious adverse events; hence, identifying those patients least likely to respond would improve the cost-benefit analysis. Finally, introduction of early, effective therapy has consistently been shown to improve long-term outcomes including joint damage, disability and employment. Aim: To identify treatment response predictors which will allow the allocation of patients to strata defined by the therapy they are most likely to respond to, early in the disease process. Methods: Two parallel workstrands (WS) will investigate synovial tissue (WS.1) and peripheral blood (WS.2) to identify biomarkers of response. Thus, in WS.1 we shall search for tissue-driven biomarkers and blood correlates in the largest synovial tissue biobank of this type (2 time points 0 & 6 months biopsy) in the world & clinical datasets (over 200 patients immediately available). In addition, in a prospective randomised clinical trial (adaptive design) we will test the hypothesis that discrete cellular and molecular signatures in the synovial tissue ("pathotypes") will enrich for response to existing biologic therapies. In WS.2, we will take advantage of the large observational cohorts of patient samples either already collected or which could be collected for minimal cost to undertake a comprehensive analysis to identify genetic, genomic, transcriptomic, proteomic or, more likely, a combination of these factors that will reliably identify responders/non-responders to each of the drugs. These collections include biological samples from over 3,000 anti-TNF-, 1,500 MTX-, 1,200 RTX- and 200 TOC-treated subjects. The two WSs are fully integrated through "multi-omic" approaches that constitute cross-cutting themes (CTs) that will converge in a large analytical and modelling package driven by experts in Bioinformatics and Statistics and allow preliminary health economic assessments of identified biomarkers. Finally, in collaboration with our Industry partners we have drawn up plans to commercialize potential diagnostics for patient benefit and wealth generation. Outcome: By the end of the study, we will have identified biomarkers of response for four of the most commonly used drugs in the treatment of RA. The study design allows a comprehensive and cohesive assault on the problem of identifying, which patients will respond best to which treatments in RA and has the potential for enormous clinical and economic impact.
Impact Medicine statistics bioinformatics multiple industry partners
Start Year 2014
 
Description MATURA consortium 
Organisation University of Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution recruitment to the STRAP trial proteomic analyses
Collaborator Contribution The overarching mission of the MATURA Consortium is to improve patient care in rheumatoid arthritis (RA) by rationalising therapy decisions through the use of a stratified medicines approach. Background: RA provides the ideal setting for the introduction of a stratified medicine approach because, first, the treatment is standardised in England through National Institute of Health and Clinical Excellence (NICE) guidance such that methotrexate (MTX) is the first choice disease modifying anti-rheumatic drug (DMARD); patients who fail to respond to MTX and at least one other DMARD are eligible for biologic TNF pathway blocking drugs (anti- TNFs) or, more recently IL6 pathway blocking drugs, tocilizumab (TOC), and those who fail to respond to anti-TNF can then be switched to the biologic B-cell depleting therapy, rituximab (RTX). Second, it is well established that there is a significant non - response rate to each drug (MTX (45% by 2 years), anti-TNF (25% by 6 months) and RTX (40% by 6 months). Third, the biologic drugs (anti-TNF, TOC and RTX) are expensive and all 4 drugs are associated with serious adverse events; hence, identifying those patients least likely to respond would improve the cost-benefit analysis. Finally, introduction of early, effective therapy has consistently been shown to improve long-term outcomes including joint damage, disability and employment. Aim: To identify treatment response predictors which will allow the allocation of patients to strata defined by the therapy they are most likely to respond to, early in the disease process. Methods: Two parallel workstrands (WS) will investigate synovial tissue (WS.1) and peripheral blood (WS.2) to identify biomarkers of response. Thus, in WS.1 we shall search for tissue-driven biomarkers and blood correlates in the largest synovial tissue biobank of this type (2 time points 0 & 6 months biopsy) in the world & clinical datasets (over 200 patients immediately available). In addition, in a prospective randomised clinical trial (adaptive design) we will test the hypothesis that discrete cellular and molecular signatures in the synovial tissue ("pathotypes") will enrich for response to existing biologic therapies. In WS.2, we will take advantage of the large observational cohorts of patient samples either already collected or which could be collected for minimal cost to undertake a comprehensive analysis to identify genetic, genomic, transcriptomic, proteomic or, more likely, a combination of these factors that will reliably identify responders/non-responders to each of the drugs. These collections include biological samples from over 3,000 anti-TNF-, 1,500 MTX-, 1,200 RTX- and 200 TOC-treated subjects. The two WSs are fully integrated through "multi-omic" approaches that constitute cross-cutting themes (CTs) that will converge in a large analytical and modelling package driven by experts in Bioinformatics and Statistics and allow preliminary health economic assessments of identified biomarkers. Finally, in collaboration with our Industry partners we have drawn up plans to commercialize potential diagnostics for patient benefit and wealth generation. Outcome: By the end of the study, we will have identified biomarkers of response for four of the most commonly used drugs in the treatment of RA. The study design allows a comprehensive and cohesive assault on the problem of identifying, which patients will respond best to which treatments in RA and has the potential for enormous clinical and economic impact.
Impact Medicine statistics bioinformatics multiple industry partners
Start Year 2014
 
Description MATURA consortium 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution recruitment to the STRAP trial proteomic analyses
Collaborator Contribution The overarching mission of the MATURA Consortium is to improve patient care in rheumatoid arthritis (RA) by rationalising therapy decisions through the use of a stratified medicines approach. Background: RA provides the ideal setting for the introduction of a stratified medicine approach because, first, the treatment is standardised in England through National Institute of Health and Clinical Excellence (NICE) guidance such that methotrexate (MTX) is the first choice disease modifying anti-rheumatic drug (DMARD); patients who fail to respond to MTX and at least one other DMARD are eligible for biologic TNF pathway blocking drugs (anti- TNFs) or, more recently IL6 pathway blocking drugs, tocilizumab (TOC), and those who fail to respond to anti-TNF can then be switched to the biologic B-cell depleting therapy, rituximab (RTX). Second, it is well established that there is a significant non - response rate to each drug (MTX (45% by 2 years), anti-TNF (25% by 6 months) and RTX (40% by 6 months). Third, the biologic drugs (anti-TNF, TOC and RTX) are expensive and all 4 drugs are associated with serious adverse events; hence, identifying those patients least likely to respond would improve the cost-benefit analysis. Finally, introduction of early, effective therapy has consistently been shown to improve long-term outcomes including joint damage, disability and employment. Aim: To identify treatment response predictors which will allow the allocation of patients to strata defined by the therapy they are most likely to respond to, early in the disease process. Methods: Two parallel workstrands (WS) will investigate synovial tissue (WS.1) and peripheral blood (WS.2) to identify biomarkers of response. Thus, in WS.1 we shall search for tissue-driven biomarkers and blood correlates in the largest synovial tissue biobank of this type (2 time points 0 & 6 months biopsy) in the world & clinical datasets (over 200 patients immediately available). In addition, in a prospective randomised clinical trial (adaptive design) we will test the hypothesis that discrete cellular and molecular signatures in the synovial tissue ("pathotypes") will enrich for response to existing biologic therapies. In WS.2, we will take advantage of the large observational cohorts of patient samples either already collected or which could be collected for minimal cost to undertake a comprehensive analysis to identify genetic, genomic, transcriptomic, proteomic or, more likely, a combination of these factors that will reliably identify responders/non-responders to each of the drugs. These collections include biological samples from over 3,000 anti-TNF-, 1,500 MTX-, 1,200 RTX- and 200 TOC-treated subjects. The two WSs are fully integrated through "multi-omic" approaches that constitute cross-cutting themes (CTs) that will converge in a large analytical and modelling package driven by experts in Bioinformatics and Statistics and allow preliminary health economic assessments of identified biomarkers. Finally, in collaboration with our Industry partners we have drawn up plans to commercialize potential diagnostics for patient benefit and wealth generation. Outcome: By the end of the study, we will have identified biomarkers of response for four of the most commonly used drugs in the treatment of RA. The study design allows a comprehensive and cohesive assault on the problem of identifying, which patients will respond best to which treatments in RA and has the potential for enormous clinical and economic impact.
Impact Medicine statistics bioinformatics multiple industry partners
Start Year 2014
 
Description MATURA consortium 
Organisation University of Sheffield
Country United Kingdom 
Sector Academic/University 
PI Contribution recruitment to the STRAP trial proteomic analyses
Collaborator Contribution The overarching mission of the MATURA Consortium is to improve patient care in rheumatoid arthritis (RA) by rationalising therapy decisions through the use of a stratified medicines approach. Background: RA provides the ideal setting for the introduction of a stratified medicine approach because, first, the treatment is standardised in England through National Institute of Health and Clinical Excellence (NICE) guidance such that methotrexate (MTX) is the first choice disease modifying anti-rheumatic drug (DMARD); patients who fail to respond to MTX and at least one other DMARD are eligible for biologic TNF pathway blocking drugs (anti- TNFs) or, more recently IL6 pathway blocking drugs, tocilizumab (TOC), and those who fail to respond to anti-TNF can then be switched to the biologic B-cell depleting therapy, rituximab (RTX). Second, it is well established that there is a significant non - response rate to each drug (MTX (45% by 2 years), anti-TNF (25% by 6 months) and RTX (40% by 6 months). Third, the biologic drugs (anti-TNF, TOC and RTX) are expensive and all 4 drugs are associated with serious adverse events; hence, identifying those patients least likely to respond would improve the cost-benefit analysis. Finally, introduction of early, effective therapy has consistently been shown to improve long-term outcomes including joint damage, disability and employment. Aim: To identify treatment response predictors which will allow the allocation of patients to strata defined by the therapy they are most likely to respond to, early in the disease process. Methods: Two parallel workstrands (WS) will investigate synovial tissue (WS.1) and peripheral blood (WS.2) to identify biomarkers of response. Thus, in WS.1 we shall search for tissue-driven biomarkers and blood correlates in the largest synovial tissue biobank of this type (2 time points 0 & 6 months biopsy) in the world & clinical datasets (over 200 patients immediately available). In addition, in a prospective randomised clinical trial (adaptive design) we will test the hypothesis that discrete cellular and molecular signatures in the synovial tissue ("pathotypes") will enrich for response to existing biologic therapies. In WS.2, we will take advantage of the large observational cohorts of patient samples either already collected or which could be collected for minimal cost to undertake a comprehensive analysis to identify genetic, genomic, transcriptomic, proteomic or, more likely, a combination of these factors that will reliably identify responders/non-responders to each of the drugs. These collections include biological samples from over 3,000 anti-TNF-, 1,500 MTX-, 1,200 RTX- and 200 TOC-treated subjects. The two WSs are fully integrated through "multi-omic" approaches that constitute cross-cutting themes (CTs) that will converge in a large analytical and modelling package driven by experts in Bioinformatics and Statistics and allow preliminary health economic assessments of identified biomarkers. Finally, in collaboration with our Industry partners we have drawn up plans to commercialize potential diagnostics for patient benefit and wealth generation. Outcome: By the end of the study, we will have identified biomarkers of response for four of the most commonly used drugs in the treatment of RA. The study design allows a comprehensive and cohesive assault on the problem of identifying, which patients will respond best to which treatments in RA and has the potential for enormous clinical and economic impact.
Impact Medicine statistics bioinformatics multiple industry partners
Start Year 2014
 
Description Medimmune 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution Research collaboration knowledge transfer and data sharing.
Collaborator Contribution Research collaboration knowledge transfer and data sharing.
Impact MedImmune are providing in kind support by providing intellectual input on using microarrays, statistical analysis of large and complex data sets from clinical studies. In addition MedImmune has an extensive history of antibody generation and biologics in diseases such as lupus, RA, asthma and COPD and will use this knowledge to support the design and interpretation of data from the consortium and to support the governance of the collaboration.
Start Year 2014
 
Description OCS Stewardship Roundtable 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution We attended the inaugural meeting to represent GCA as a rare disease that is treated with steroids. We raised awareness of the condition and its treatment. We provided links to some of our TARGET members who have held follow-up conversations.
Collaborator Contribution On 5 November 2019, AstraZeneca UK hosted a roundtable under its PRECISION programme to explore issues surrounding the use of oral corticosteroids (OCS) for patients living with inflammatory conditions in the UK. Objectives for the meeting were to: 1. Understand the drivers for and ambitions that bring attendees to this OCS stewardship roundtable 2. Begin to mutually define, recognise and articulate the health and quality of life impact that long-term OCS use has on patients across different disease areas 3. Identify shared challenges associated with long-term OCS use across different disease areas (for example, issues in common at different points along the pathway) 4. Discuss and agree possible long-term collaborative objectives and activity, to be further explored in follow-up, as appropriate
Impact We attended a single meeting and have been invited to follow up events. We have set up calls with the AstraZeneca team and TARGET members to discuss health economic and epidemiological approaches.
Start Year 2019
 
Description PEAC Genotypic analysis of Methotrexate responsiveness 
Organisation University of Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution Provided DNA samples from MTX responders and non-responders for analysis
Collaborator Contribution Genetic analysis including methylation studies
Impact Work ongoing
Start Year 2015
 
Description Pfizer 
Organisation Pfizer Ltd
Country United Kingdom 
Sector Private 
PI Contribution Research collaboration and data sharing. The collaboration will enable the proposed study to be undertaken by providing drug that will allow for comparison of response within the proposed subsets of rheumatoid arthritis. In addition, the collaboration between the consortium and industry in the design of the trial will lead to an optimized study protocol. Lastly, analysis of the samples will enable exploratory biomarker research to identify new, non-invasive, biomarkers and potential companion diagnostics.
Collaborator Contribution We are running the research study and sharing data.
Impact Full support in providing STRAP clinical trial IMP Etanercept.
Start Year 2014
 
Description Pharmatics 
Organisation Pharmatics Limited
Country United Kingdom 
Sector Private 
PI Contribution MATURA will provide samples from RA patients treated with biologics, samples from responders and non-responders will be analysed by Pharmatics using machine learning to identify candidate biomarkers.
Collaborator Contribution Pharmatics will provide analytical services using machine learning techniques.
Impact Too early
Start Year 2016
 
Description Protagen 
Organisation Protagen AG
Country Germany 
Sector Private 
PI Contribution Thoroughly characterized samples with well documented clinical and laboratory data will be provided by the MATURA-consortium It is planned, that the MATURA consortium will provide the required number of samples for a statistical significant result.
Collaborator Contribution Analysis of Autoantibodies as Biomarkers for RA Treatment Response To Biological Drugs and MTX in Samples from the MATURA through making the SeroTag-technology available for the detection of initially 400 autoantibodies in biological fluid of RA patients.
Impact work ongoing
Start Year 2015
 
Description Qiagen 
Organisation Qiagen
Country Netherlands 
Sector Private 
PI Contribution Research collaboration has resulted in agreement to advance knowledge transfer and data sharing between partners.
Collaborator Contribution Have given support in developing a more accurate understanding of the mechanisms driving RA to inform clinically relevant developments of diagnostic algorithms and stratify patients to the most appropriate therapy. Have given support in developing molecular assays which could be used for investigational purposes within the MATURA collaboration. On selection and verification of the appropriate biomarkers and with supporting clinical evidence generated through the MATURA infrastructure, resources and patient cohorts QIAGEN Manchester may then initiate the development of diagnostic products for immediate clinical utility. The diagnostics products could be prognostic for classifying disease subtype and severity or predictive (companion diagnostics) for guiding therapy selection and treatment of patients
Impact The contribution of QIAGEN will be the training and transfer of know-how in the product development of molecular diagnostics to the required technical, regulatory and quality standards necessary for transfer for verification and manufacturing of a diagnostic product.
Start Year 2014
 
Description Rituximab FCGR Pharmacogenetics programme 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Professors Ann Morgan and Jenny Barrett and Dr Jim Robinson are leading the Fc gamma receptor pharmacogenetics project on behalf of MATURA. They have established and validated a MLPA genotyping platform for the FCGR genetic locus and identified an association with response to rituximab in rheumatoid arthritis. They are now establishing collaborations with other groups to explore this in other disease groups. Preliminary work in Leeds has demonstrated that the same FCGR association with B cell depletion and clinical response is observed in SLE and this work is now being expanded to larger cohorts in other autoimmune diseases and other B cell depleting therapies.
Collaborator Contribution Professor Tim Vyse and Dr Ed Vital, both participants of MASTERPLANS, lead a number of national and international projects in SLE, including some cohorts collected through MASTERPLANS. Funding has been identified to undertake some preliminary work on the SLE cohorts treated with rituximab using the same genotyping platform as developed for MATURA. We are also exploring extending this study to other B cell depleting antibodies used in SLE.
Impact Professors Ann Morgan and Tim Vyse have long standing interests in FCGR genetics and their groups have had informal discussions, examined PhDs over many years. In this new collaboration they plan to bring their existing knowledge to explore FCGR pharmacogenetics across different inflammatory diseases. Professor Ann Morgan and Dr Ed Vital have both contributed to the Leeds rituximab study and contributed to the establishment of the Leeds rituximab pharmacogenetics programme.
Start Year 2017
 
Description Sanofi MATURA 
Organisation Sanofi
Country Global 
Sector Private 
PI Contribution Providing data and samples from the MATURA project
Collaborator Contribution Analyses of data to investigate biomarkers of response/non-response which may lead to the identification of new drug targets and/or diagnostic tests to identify optimal treatment regimes
Impact No outcomes to date
Start Year 2020
 
Title Stratification of Therapy for Rheumatoid Arthritis by Pathobiology (STRAP) Clinical Trial 
Description This study will aim to test the utility of synovial histopathology and cell type as a potential biomarker to guide therapeutic decisions in RA patients failing DMARD therapy and started on Rituximab, Tocilizumab or Etanercept therapy. Specifically, can a diagnostic synovial biopsy showing a B-cell "rich/poor pathotype" define specific disease responsive/resistant subsets for patient stratification and help rationalise biologic drug choice? The trial is currently under review by the REC and MHRA and is jointly funded by the MRC and ARUK. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2019
Development Status Under active development/distribution
Impact The aim is to provide a tailored approach to treatment decisions in patients at this stage of their disease, in order to maximise their potential response to therapy. The following are notable impacts arising from trial development: 1. STRAP Protocol complete and patient related documents review by Queen Mary patient advisory group. 3. Clinical Database: testing underway. 4. REC and MHRA submitted. REC meeting 13th Nov 5. 5. TMG formed and convenes frequently TSC will be in line with timelines. 6. STRAP website launched. 7. Investigators Meeting 17th September 2014. 
URL http://www.matura-mrc.whri.qmul.ac.uk
 
Title BioT-App 
Description Application developed for patients to monitor disease activity using the DAS28 outcome measure Patients report joint swelling & tenderness, measures of well being and adverse events, this information is captured centrally 
Type Of Technology Software 
Year Produced 2018 
Impact Too early , will be applied to future clinical trials to enable real time monitoring of patients , providing more accurate information and potentially reducing the costs of running trials by reducing the number of unperson visits required. 
 
Description "Bones" Exhibition at the Great North Museum 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Workshops, demonstrations, talk, events and public information materials presented in parallel with the Bones Exhibition at the Great North Museum highlighting musculoskeletal research at our Centres of Excellence at Newcastle University including the Centre for Integrated Musculoskeletal Ageing, the Newcastle Experimental Arthritis Treatment Centre, the Rheumatoid Arthritis Centre of Excellence and the Newcastle Biomedical Research Centre.
Year(s) Of Engagement Activity 2017
URL https://greatnorthmuseum.org.uk/whats-on/bones-skeleton-secrets-of-the-animal-world
 
Description 3TR Kick off meeting Oct 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 Over 200 researchers attended the opening meeting of the 'Taxonomy, Treatment, Targets and Remission, 3TR" kick-off meeting
3TR (Taxonomy, Treatment, Targets and Remission) is the largest-ever Innovative Medicine Initiative 2 (IMI2) immunology project and aims to improve disease management of non-responders to therapy across seven immune-mediated diseases. The 3TR project will focus on the identification of the molecular mechanisms of non-response to treatments, relapses and remission in autoimmune, inflammatory, and allergic conditions. Queen Mary is one of the 69 academic and industry partner institutions participating in this project (total funding €80M over 7 years) analysing multi-omics data from patient cohorts suffering from seven different inflammatory diseases.
Professor Costantino Pitzalis will lead and coordinate the Rheumatoid Arthritis (RA) research, generating and analysing data from both existing cohorts ( see PEAC, MATURA,R4RA ) and through the collection of new samples, including synovial tissue from 400 patients, in nine centres across Europe and he co-leads the Ethics work stream. The kick-off meeting was held in Granada at the end of October 2019 and the project will run for seven years, with the aim of advancing the prediction of response/non-response to therapy and hence to improve patient outcomes. Prof Pitzalis coordinated discussions on the RA research plan and reported these to the whole group. A presentation on Ethics was also made by J Peel on behalf of Prof Pitzalis.
Year(s) Of Engagement Activity 2019
URL https://www.3tr-imi.eu
 
Description Appointment of Lay Chair to the MATURA Patient Advisory Group and regular meetings with Lay Chair 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Participants in your research and patient groups
Results and Impact Review of STRAP patient information documents by Lay Chair. Development of strategy for MPAG and organisation of the group as well as sourcing members using the Chair's links with other patient organisations.


Amendments and changes were made to documents which have been implemented.
Year(s) Of Engagement Activity 2014
 
Description Arthritis stand at the Bart's & QMUL Science Festival 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact The festival, aimed at secondary schools and young people interested in a career in science and medicine, was held at QMUL's Mile End campus on the 21 June .
Students from schools across London attended the seventh edition of the festival which was supported by the National Institute for Health Research (NIHR), the Biomedical Research Centre (Barts BRC), the NHS Trust and Trials Connect. EMR coordinated a stand to provide children with an opportunity to learn more about arthritis, this included; Posters on the difference between RA & OA; simulation gloves to mimic the effect of arthritis on dexterity , ultrasound scans so that children could 'see inside their joints'. Members of NRAS & ARUK helped on the day with the exhibition.
Year(s) Of Engagement Activity 2017,2018,2019
URL http://www.qmul.ac.uk/media/news/items/smd/198594.html
 
Description MATURA Lay Summaries of Publications 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact Lay summaries of publications have been made available on the MATURA website so that the results can be widely disseminated to a range of audiences
Year(s) Of Engagement Activity 2018,2019
URL http://www.matura.whri.qmul.ac.uk/news.php
 
Description MATURA Operational 
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 Monthly teleconferences of the STRAP (WS1) and Biostats (WS2) teams.
Quarterly Project Steering Groups
Bi-annual Consortium Management Board meetings
Annual Scientific Conference
Year(s) Of Engagement Activity 2014,2015,2016,2017,2018,2019
 
Description MATURA Patient Advisory Group (MPAG), meeting 10th December 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact to be updated after event
Year(s) Of Engagement Activity 2014
URL http://www.matura.whri.qmul.ac.uk/what_is_matura.php
 
Description MATURA Patient Advisory Group - Minutes of meetings published on website 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact To make information readily accessible
Includes presentations made by researchers to the patient group
Year(s) Of Engagement Activity 2014,2015,2016,2017,2018,2019
URL http://www.matura.whri.qmul.ac.uk/get_involved_mpag.php
 
Description MATURA Patient Advisory Group presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Findings from work carried out in MATURA relating to blood biomarkers to predict response to therapy in patients with rheumatoid arthritis were presented, generating considerable discussion. Specifically, the group were asked to comment on planned questions for a discrete choice experiment and made valuable suggestions.
Year(s) Of Engagement Activity 2016
 
Description MATURA Public Launch Symposium 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Increased awareness of the programme
Potential collaborators, academic and commercial, identified.

To be updated after event
Year(s) Of Engagement Activity 2015
URL http://www.matura.whri.qmul.ac.uk/files/News/MATURA_Public_Launch_Symposium_090115.pdf
 
Description MATURA Scientific Symposium 
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 MATURA consortium partners, academic and commercial, presented on current progress with projects to:
1. Share information 2. Identify further areas for collaboration best practice 3. Obtain feedback from the Scientific Advisory Panel (SAB)
Outcomes included: 1.In-depth informed discussion 2. Identification of sharing procedures across international consortia 3. Ideas for future research 4. A positive feedback report from the SAB.
Year(s) Of Engagement Activity 2016,2017,2018,2019
 
Description MATURA Website 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The MATURA website provides information to the public, patients and professionals on the consortium's members, objectives and research projects. News items are regularly added and the site has a PPI page which has been designed and written by patients. Potential partners, both academic and commercial, can access the process for joining/requesting samples and the relevant application forms.

For consortium members there is a secure document repository area.
Year(s) Of Engagement Activity 2015,2016,2017,2018
URL http://www.matura.whri.qmul.ac.uk
 
Description MATURA article in NRAS Magazine spring 2017 & spring 2018 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Article in NRAS magazine purpose was to engage RA patients and carers in the potential of stratified medicines. Resulted in enquiries about the clinical trial, STRAP, and in patients volunteering to join the MATURA patient advisory group
Year(s) Of Engagement Activity 2017,2018
URL https://www.nras.org.uk/data/files/Membership/Members%20Area/27642%20NRAS%20Magazine%20Spring%202017...
 
Description MPAG Patient Group Meetings 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact To involve and engage RA patients in the stratified medicine research programme
Year(s) Of Engagement Activity 2015,2016,2017,2018,2020
URL http://www.matura.whri.qmul.ac.uk/what_is_matura.php
 
Description MRC RA-MAP CMB and PSG Meetings London 2016 
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 Strategic planning around future research directed at predictors of remission in RA.
Year(s) Of Engagement Activity 2016
 
Description MSK TRC Springboard 2020 
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 Chaired by Prof C Pitzalis To develop innovative strategies that will increase MSK research across various specialities including preliminary talks and overarching workstream meetings for discussions around future development and projects.
Year(s) Of Engagement Activity 2020
 
Description Meet the Researcher Event QMUL 
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 Patients, carers and/or patient groups
Results and Impact Patients and carers invited to visit laboratories to meet researchers and see their work, this also allowed laboratory researchers to meet patients . Researchers also manned stands to educate patients and carers on research projects . MATURA patient advisory group manned a stand that allowed researchers to meet them and to try on gloves that simulate having arthritis. Followed by a BBQ to allow informal conversations and greater insights for both groups.
Year(s) Of Engagement Activity 2017,2018
URL http://www.qmul.ac.uk/citi/patient-and-public-engagement/
 
Description Oldham Gallery PPIE event "The Future in their Hands" exhibition evening 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Opening event for a photographic exhibition called "The Future in their Hands" raising awareness of Rheumatoid Arthritis and engagement of patients on how they cope with often debilitating conditions.
Year(s) Of Engagement Activity 2017
 
Description Portuguese Society of Rheumatology - Algarve 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Keynote Lecture - New Treatments for IMID - invited paper to Annals Review
Year(s) Of Engagement Activity 2016
 
Description Precision Medicine UK 
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 NOCRI joined UK leaders in the research, development and commercialisation of precision medicine for a one-day event this week designed to encourage new partnerships and highlight new opportunities in the field. The Precision Medicine UK: Collaboration Nation event at De Vere Holborn Bars, London, on 9 December was organised on behalf of the Stratified Medicine Innovation Platform by Innovate UK,, National Institute for Health Research, Cancer Research UK,Medical Research Council, Invest Northern Ireland, Health and Care Research Wales and the Knowledge Transfer Network, with the NIHR Office for Clinical Research Infrastructure (NOCRI) coordinating the NIHR's involvement. The day formed part of a programme to make the UK a world leader in precision medicine and provided real-world examples of the discovery and development of precision medicine solutions, through talks, panel discussions, workshops and exhibitions with the opportunity to arrange one-to-one partnering meetings. Precision medicine is an emerging approach to the treatment and diagnosis of disease that takes into account variations in a patient's genes, environment and lifestyle. It aims to better target treatments to an individual's circumstances to improve outcomes for patients. Representatives from across the NIHR were involved in the day and presented on a range of projects and funding programmes. Professor Bryan Williams of NIHR UCLH Biomedical Research Centre joined the first panel of the day which highlighted UK investments in the invention and evaluation phase of research. Professor Williams' highlighted key NIHR's investments in this space and provided examples of exciting precision medicine projects from UCLH BRC. In addition, a number of NIHR precision medicine projects were presented during the disease area specific showcase sessions. This included Professor Costantino Pitzalis who presented the THERAPIST study on behalf of the NIHR Translational Research Partnership, Professor Simon Mead's who presented a project at NIHR Queen's Square Biomedical Research Unit on the "dementia chip" and Professor Tariq Sadiq's who presented on Capacity Building and Delivery of Precision Medicine in Sexual Health, through NIHR Funding. Mark Samuels, Managing Director of NOCRI, also chaired a discussion panel themed 'Enabling Collaboration', which highlighted the value of collaborative working between companies, academics, charities and patients. The event saw the launch by the chief executive of Innovate UK, Dr Ruth McKernan, of a new map of the precision medicine landscape. A whole range of organisations, including charities, health bodies and devolved administrations are coordinating their work under the umbrella of Innovate UK's Stratified Medicine Innovation Platform, with NOCRI representing the NIHR.
Year(s) Of Engagement Activity 2015
 
Description Queen Mary Trial Advisory Group (QMTAG) review of STRAP patient information documents 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Participants in your research and patient groups
Results and Impact Review of STRAP patient information documents by patient group.




Documents were discussed and suggestions for changes made to patient information.
Amendments and changes to patient documents have been implemented.
Year(s) Of Engagement Activity 2014
 
Description R4-RA & STRAP Trials Investigators Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 28 attendees from 15 UK centres have attended the Investigators Meeting. There were presentations as well as workshop for US assessment and eCRF training.

Since the initial meeting online meetings have been held and include international sites

The meeting successfully resulted in engagement with investigators who are currently participating or interested in participating in the trial, which is expected to enhance a successful delivery of the trial.
Year(s) Of Engagement Activity 2014,2015,2016,2017
 
Description STRAP Newsletters 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Monthly newsletter to inform staff at participating hospitals and industry partners of current progress, upcoming meetings, best practice and an overview of updates to study documentation.
Year(s) Of Engagement Activity 2015,2016,2017,2018
 
Description STRAP eligibility cards 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Credit cards were designed and printed to remind practitioners of the eligibility criteria for patients to participate in the STRAP trial. The cards are worn on lanyards.
Year(s) Of Engagement Activity 2016,2017,2018
 
Description STRAP posters 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact Posters were designed and printed for display in rheumatology clinics where the STRAP study is recruiting patients. The design is also used on display screens in clinics.
Year(s) Of Engagement Activity 2016,2017,2018
 
Description School visits (South Yorkshire) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Dr Jim Robinson from the University of Leeds has presented at 3 schools in the South Yorkshire region on a range of topics with the primary objective being to encourage school children to consider careers in science. He has brought in the concepts of human health, genetics and personalised medicine into these talks.
Year(s) Of Engagement Activity 2018,2019
 
Description Stratification of Therapy for RA by Pathobiology (STRAP) website 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The STRAP website provides provides information to the public, patients and professionals on:
The study objectives
The study investigators and core team
Study overview - including the visit schedule
Participating hospitals
Recruitment updates




Research investigators have a common central platform from which to gain new information and new research nurses have looked at the site to learn about the study. Please see: http://www.matura-mrc.whri.qmul.ac.uk/
Year(s) Of Engagement Activity 2014,2015,2016,2017,2018
URL http://www.matura-mrc.whri.qmul.ac.uk/
 
Description Stratified Medicine Engagement Event - Glasgow 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact Patient engagement event to increase awareness of the potential for stratified medicines in the treatment of rheumatoid arthritis.
Presentations on the general principles and research studies ongoing in the local area were followed by discussions initiated by the audience.
Year(s) Of Engagement Activity 2016
 
Description Stratified Medicine Engagement Event - Leeds 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact Patient engagement event to increase awareness of the potential for stratified medicines in the treatment of rheumatoid arthritis.
Presentations on the general principles and research studies ongoing in the local area were followed by discussions initiated by the audience.
Year(s) Of Engagement Activity 2016
 
Description Stratified Medicine Engagement Event - Newcastle 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact Patient engagement event to increase awareness of the potential for stratified medicines in the treatment of rheumatoid arthritis.
Presentations on the general principles and research studies ongoing in the local area were followed by discussions initiated by the audience.
Year(s) Of Engagement Activity 2016
 
Description Stratified Medicine Engagement Event - Oxford 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact Patient engagement event to increase awareness of the potential for stratified medicines in the treatment of rheumatoid arthritis.
Presentations on the general principles and research studies ongoing in the local area were followed by discussions initiated by the audience.
Year(s) Of Engagement Activity 2016
 
Description Stratified Medicine Leaflets 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact A leaflet was designed and printed for distribution at patient events e.g. NRAS meetings and at hospital clinics to increase the understanding and awareness of the potential for stratified medicines in the treatment of rheumatoid arthritis.
Year(s) Of Engagement Activity 2017,2018
 
Description Tate Exchange "Creating without constraint. Arthritis and art" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Participated in "IDEAS IN MOTION: BORDERS, BODIES, AND THE UNIVERSE WITH QUEEN MARY UNIVERSITY OF LONDON
11-16 JUNE 2019" with a workshop on:

Creating without Constraint: Arthritis and Art
Members of the public were invited to to experience an interactive workshop exploring the relationship between impaired mobility and artistic expression. Our researchers will guide you in a 'journey' inside the joints with activities simulating the restriction of movement. The display will include the work of Renoir and Pickering, two artists who lived with arthritis, to explore how art can overcome disability. Also, emerging painter Rebecca Ivatts will give a talk about her collaboration with Pickering.
Year(s) Of Engagement Activity 2019
URL https://www.tate.org.uk/whats-on/tate-modern/tate-exchange/workshop/ideas-motion-borders-bodies-and-...
 
Description Video of patient describing synovial biopsy procedure 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact Video produced of patient being interviewed about the experience of having a synovial biopsy. Purpose - to answer patient (RA) questions and concerns about undergoing a synovial biopsy for a research study. Video posted on STRAP and R4RA websites and used widely in outpatient clinic waiting rooms where a screen is available
Year(s) Of Engagement Activity 2017
URL http://www.matura-mrc.whri.qmul.ac.uk/ultrasound_guided_synovial_biopsy_taking_a_biopsy.php