MICA: Treatment According to Response in Giant cEll arTeritis (TARGET)

Lead Research Organisation: University of Leeds
Department Name: School of Medicine

Abstract

Rare diseases like the autoimmune disease giant cell arteritis (GCA) are at risk of not getting the attention they deserve in research funding. In GCA, blood vessels become inflamed and blocked. Without treatment, this can lead to blindness, strokes and tearing or bursting of major blood vessels, such as the aorta. However, this does not affect all patients and this disease shows great variation in severity between different individuals. Prompt treatment is critical in order to prevent permanent tissue damage and loss of vision but, because the disease is rare, the symptoms can be unfamiliar to busy family doctors and early warnings of this diagnosis can be missed for some weeks or months.

Currently all patients are treated with steroids at high doses, but this is a non-specific treatment that causes dangerous side effects in a very large proportion of patients (86%). These include high blood pressure, diabetes, mental-health problems, muscle weakness and fragile skin and bones, leading to breaks. This is particularly serious because GCA affects older people (>50 years) who often have other medical conditions. There is virtually no clinical trial evidence to guide doctors as to how quickly they should be reducing the steroid dose, how long treatment should be continued and the benefits of using other immune-suppressing drugs to minimise steroid requirements. Treatment trials traditionally lump all GCA patients together and have so far failed to convincingly demonstate improved outcomes when these alternative treatments have been added to steroids. We propose that by accurately classifying patients in terms of their pattern of disease, dominant immune pathway and risk for developing steroid side effects, will allow us to identify subgroups of patients who will respond better than others to newer therapies. We will also use outcome measure assessment to identify good prognosis, non-relapsing groups who may require lower steroid doses for shorter durations; allowing us to minimize therapy and reduce toxicity in those patients whose disease is under better control. GCA is sufficiently rare that no single centre can access sufficient numbers of patients to perform the analyses required at the necessary scale. There is therefore a compelling need for a national partnership approach, capitalising on key UK strengths and building on recent experience of succesful delivery of large, collaborative studies in other rare diseases that have already delivered new treatments for use in the NHS.

Our proposed partnership will bring together specialist GCA clinicians and researchers from across the UK so that they can work together to tackle the causes, diagnosis and treatment of GCA. We already have the consent and active engagement of many patients with GCA and the partnership will expand this to create a comprehensive patient network across the UK. The funding will provide state-of-the-art infrastructure, including equipment and staff to manage the clinical data collected, x-rays and scans, along with data collected from blood and tissue biopsies; irrespective of whether the tests were performed within the NHS or for research. The Partnership will make use of a substantial MRC investment in computing power and bioinformatics at the University of Leeds and Leeds Teaching Hospitals NHS Trust to safely store and manage these data. The proposed research activity will make a world-leading contribution to the discovery of better diagnostic tests for use in the NHS. It will also attract investment and research to the UK from the pharmaceutical industry who will work closely with the partnership to develop new treatment strategies for GCA. The approach developed by the partnership will provide an exemplar to inform future consolidation of rare disease research around state-of-the-art bioinformatics infrastructure.

Technical Summary

Giant cell arteritis (GCA) is the commonest primary systemic vasculitis. Ischaemic complications, including visual loss, occur in 19%. Large-vessel vasculitis leads to stenoses and aneurysms. GCA is difficult to diagnose; to prevent blindness, suspected GCA is treated empirically with high-dose glucocorticoids. However blood and imaging tests can normalize within days of therapy, whereas temporal artery biopsy is insensitive. 86% of patients have adverse effects with glucocorticoids. Glucocorticoids can trigger psychosis or arrhythmia within days, prompting further admissions and treatments. Many other adverse events accrue over time and 50% still need glucocorticoids at 2-3 years. There is little trial data to guide adjunctive immunosuppression, and these data are equivocal due to patient heterogeneity and imprecision of outcomes.
We will develop methods for phenotyping patients to accurately identify the severity of organ involvement, the dominant immunological pathways, and risk factors for glucocorticoid toxicity. Integrating this information, leveraging existing and current datasets, will allow modelling of the most appropriate treatment pathways and rational patient stratification. We will also use outcome measures to identify good prognosis, non-relapsing groups in order to minimize therapy and reduce toxicity in these patients. Refinement of the molecular and immunological phenotype will also allow rational patient selection for early-phase clinical trials of selected biological therapies supporting drug repurposing, subject to target validation.
In parallel, we will generate contemporary epidemiological data to support clinical adoption of emerging biomarkers or therapeutic strategies through incorporation of health economic and cost-effectiveness analyses and engagement with NICE. Future work will include the development of virtual training material and expert centres, supported by NHS England, through specialist commissioning centres.

Planned Impact

Our overarching vision is to improve health and reduce health inequalities for patients with GCA. To achieve this, we recognise the need to understand and identify our end users' needs and to map these against our interdisciplinary strengths in translational research and provide focus for our work. We identify our main beneficiaries as clinicians delivering care, patients and users of health services, government and healthcare policy makers who determine the configuration and funding of health services and healthcare related industries, especially in the pharmaceutical, devices and informatics sectors. Our main impacts are on the clinical and cost effective delivery of health services and on the economy and commercial activities of healthcare related industries. We recognise that the strongest potential for impact arises when our strengths in clinical, biomedical and applied health research converge to address important clinical challenges.

Patients, Government and Healthcare Policy makers: The impact of developing new diagnostic and stratification algorithms that will identify those patients most likely to require and respond to a specific therapy, in the absence of serious toxicities, will revolutionise the delivery of GCA healthcare services. Permanent loss of vision and stroke can have a major impact on quality of life and ultimately independence, particularly in this elderly population. The societal impacts and social inclusion for individuals with the disease and their relatives is immense. More timely and accurate diagnosis and efficacious and/or cost-effective treatment, would have significant impacts on the NHS and Social Services and thus ultimately the UK economy.

UK Economy and Industry: The UK is a world leader in life sciences. Medical technology development and innovation is a growing business sector that has the potential to stimulate the UK economy and revolutionise healthcare provision through accelerated delivery of stratified medicines. The University of Leeds has restructured its innovation services to align with 14 industry sectors and the newly established Stratified Medicine Hub (part of the Healthcare Innovation Hub) and its team of innovation professionals will play a key role in establishing links between our Partnership and potential commercial partners by using existing networks and developing new contacts to provide support for stakeholder engagement. At the time of application six industrial partners have signed up and discussions are ongoing with three additional pharmaceutical companies. Opportunities for collaboration will be identified through knowledge of partnership members, review of commercial product pipelines, clinical trial databases and patent searches. In addition to the direct contact with industry in the preparation of this application, Prof Luqmani and Dr Jayne are in ongoing discussions with NOCRI to facilitate clinical trials in GCA, through the Translational Research Partnership.

GCA is also of interest to diagnostic companies, as the potential for identifying disease-specific markers of risk or treatment response, as well as general markers of inflammatory disease, is appealing. Alongside the mechanisms listed above, the partnership will utilise its network to identify and engage new partners and can also promote the partnership through contacts within the British In Vitro Diagnostics Association (BIVDA). A workshop with BIVDA including representation from the Technology Strategy Board and Precision Medicine Catapult was held in June 2014, with 15 companies attending that led to three industrial partners supporting this application. We will continue to engage with the Precision Medicine Catapult once this has been fully implemented.

Publications

10 25 50
 
Description Co-chair of guideline group - developing national guidelines for Giant Cell Arteritis management, with the British Society for Rheumatology
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
Impact These NICE-endorsed clinical practice guidelines on diagnosis and treatment of giant cell arteritis were published in January, 2020. This prompted significant coverage both via social media and in print media. A podcast was also made by the journal Rheumatology featuring an interview with me. Many commenters on social media stated that they found the guidance useful for their clinical practice. An opinion piece was written in the Guardian newspaper which mentioned some of the key aspects of the guidance such as the need to be seen by a specialist promptly on suspicion of giant cell arteritis.
 
Description Co-chair of the European League Against Rheumatism Committee to update guidelines for management of large vessel vasculitis
Geographic Reach Europe 
Policy Influence Type Membership of a guideline committee
 
Description Co-submission of the Clinical Reference Group application to assess the clinical and cost effectiveness of Tocilizumab in subsets of patients with severe GCA
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description Contribution to the British Society of Rheumatology response to the NICE Consultation for Tocilizumab in Giant Cell Arteritis
Geographic Reach National 
Policy Influence Type Participation in a national consultation
 
Description OMERACT - Polymyalgia Rheumatica Working Group
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description Academy of Medical Sciences Springboard Award - The regulation of skin function and wound healing by pre-receptor glucocorticoid metabolism
Amount £100,000 (GBP)
Organisation Academy of Medical Sciences (AMS) 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2019 
End 07/2021
 
Description BIOlogics in refractory VASsculitis (BIOVAS): A pragmatic, randomised, double-blind, placebo-controlled, modified-crossover trial of biologic therapy for refractory vasculitis in adults and children
Amount £1,956,458 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 09/2019 
End 08/2025
 
Description Clinical Research Career Development Fellowship
Amount £638,126 (GBP)
Funding ID 214539/Z/18/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2019 
End 09/2023
 
Description Conference Grant: TARGET Annual Scientific Meeting 2019
Amount £5,000 (GBP)
Organisation F. Hoffmann-La Roche AG 
Sector Private
Country Global
Start 09/2019 
End 09/2019
 
Description Confidence in Concept
Amount £50,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 02/2019 
End 09/2019
 
Description Confidence in Concept (Development of a molecular diagnostic for accurate quantification of T-cell polarisation to inform treatment stratification and drug repurposing opportunities)
Amount £50,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 12/2017 
End 11/2018
 
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 Development and validation of a patient reported outcome measure for Giant Cell Arteritis
Amount £149,274 (GBP)
Funding ID PB-PG-1217-20017 
Organisation NIHR/HEFCE Higher Education Fund for England 
Sector Public
Country United Kingdom
Start 10/2019 
End 09/2021
 
Description Dissecting the role of multinucleated giant cells in the pathogenesis of Giant Cell Arteritis
Amount £656,210 (GBP)
Funding ID 214539/Z/18/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2019 
End 10/2023
 
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 Investigator Initiated Study Scheme
Amount £958,765 (GBP)
Organisation F. Hoffmann-La Roche AG 
Sector Private
Country Global
Start 03/2019 
End 09/2022
 
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 Medical Research Council Confidence in Concept award - Integrated system for rigorous quantification of uncertainty in personalised diagnosis and patient counselling in GCA
Amount £49,990 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 12/2018 
End 05/2019
 
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 National Consortium of Intelligent Medical Imaging (NCIMI)
Amount £9,633,796 (GBP)
Funding ID 104688 
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 01/2019 
End 12/2021
 
Description Northern pathology imaging co-operative (NPIC)
Amount £17,200,000 (GBP)
Funding ID 104687 
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 02/2019 
End 03/2022
 
Description Post-translational protein modification profiling screen of serum samples taken from patients with giant cell arteritis (GCA) and age and gender-matched controls
Amount £20,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 02/2020 
End 01/2021
 
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 Proximity to Discovery - Pump Priming Award
Amount £12,705 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2018 
End 06/2018
 
Description Scientific Meeting support
Amount £10,000 (GBP)
Organisation F. Hoffmann-La Roche AG 
Sector Private
Country Global
Start 10/2018 
End 10/2018
 
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
 
Description Springboard Award: Regulation of skin function and wound healing by pre-receptor glucocorticoid metabolism in diabetes
Amount £106,954 (GBP)
Organisation Academy of Medical Sciences (AMS) 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2019 
End 08/2021
 
Description TARGET Consortium Biobank
Amount £49,473 (GBP)
Funding ID 118238 
Organisation Vasculitis UK 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2020 
End 01/2022
 
Description UKIVAS Infrastructure support
Amount £106,000 (GBP)
Organisation Vifor Pharma 
Sector Private
Country Switzerland
Start 01/2019 
End 12/2019
 
Description UKIVAS Infrastructure support
Amount £59,000 (GBP)
Organisation Vifor Pharma 
Sector Private
Country Switzerland
Start 05/2018 
End 12/2018
 
Description UKRI Centre for Doctoral Training in Artificial Intelligence for Medical Diagnosis and Care
Amount £5,900,000 (GBP)
Funding ID EP/S024336/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 09/2019 
End 08/2028
 
Title A genome-wide association study - polymyalgia rheumatica 
Description To date little is known about the genetics of polymyalgia rheumatica (PMR). A genome-wide association study (GWAS) based on electronic health records with a discovery cohort including 413 cases of PMR showed evidence of association with variants in the HLA region reaching genome-wide significance (Mosley et al, 2016; Nature Communications 7:11433). 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2018 
Provided To Others? No  
Impact We have used data from UK Biobank to carry out a GWAS of self-reported PMR. After quality control, 929 cases were identified who reported at recruitment or first follow-up that they had ever been diagnosed with PMR. A GWAS was conducted comparing these to controls, frequency-matched 10:1 on age and sex. As expected, clear associations with genetic variants in the HLA region were seen reaching genome-wide significance. As part of her PhD project, Charikleia Chatzigeorgiou is combining the results of this GWAS of PMR with the results of a GWAS of giant cell arteritis she has conducted, with the aims of (i) boosting the power to identify new genetic variants associated with both diseases and (ii) better understanding the joint genetic architecture of these traits. 
 
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 Rheumatology Assessment Database Innovation in Oxford (RhADIO) 
Description RhADIO facilitated accurate and comprehensive assessment and data collection in patients with complex autoimmune rheumatic diseases and ensured compliance with NHS England commissioning policies and CQUIN targets were achieved. RhADIO, so far, has captured over 31,000 encounters from >12,000 patients. It can be accessed from multiple locations in sites across the Trust and peripheral hospitals e.g. Banbury, Witney, Bicester. The Oxford University NHS Foundation Trust Cerner team have agreed to incorporate RhADIO into the electronic patient record (EPR). 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2019 
Provided To Others? No  
Impact It will facilitate clinical care; provide commissioning for Quality and Innovation (CQUIN) for autoimmune rheumatic diseases; phenotype and identify potential subjects for approach by research teams. 
 
Title Scoring system for temporal artery biopsies 
Description A standardised scoring system for classifying temporal artery biopsies from routine clinical practice (haematoxylin and eosin stained sections) is being developed with Dr Aruna Chakrabarty (Consultant Neuropathologist, Leeds NHS Trust). This will allow more accurate phenotyping of relevant pathotypes of giant cell arteritis and when combined with other analysis techniques it will better inform our understanding of pathogenic pathways. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2017 
Provided To Others? No  
Impact This project is under development and further outcomes will be presented in the next report. 
 
Title Ultrasound evaluation of temporal and axillary arteries 
Description Ultrasound examination of blood vessels requires training to ensure accurate assessment. We have described the methodology recommended (Monti S, Floris A, Ponte C, Schmidt WA, Diamantopoulos AP, Pereira C, Piper J, Luqmani R. The use of ultrasound to assess giant cell arteritis: review of the current evidence and practical guide for the rheumatologist. Rheumatology (Oxford). 2018 Feb 1;57(2):227-235.) 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2019 
Provided To Others? Yes  
Impact Improvement in ability to diagnose temporal arteritis, avoiding need for biopsy (Luqmani R, Lee E, Singh S, Gillett M, Schmidt WA, Bradburn M, Dasgupta B, Diamantopoulos AP, Forrester-Barker W, Hamilton W, Masters S, McDonald B, McNally E, Pease C, Piper J, Salmon J, Wailoo A, Wolfe K, Hutchings A. The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (TABUL): a diagnostic accuracy and cost-effectiveness study. 
 
Title A synoptic system for reporting of temporal artery biopsies 
Description We investigated consistency of reporting between different pathologists, and propose a solution.Methods. (1) An audit of UK pathologists was conducted. 9 digital images of temporal artery transverse sections stained with haematoxylin and eosin (H&E) were presented, with a choice of 4 diagnostic categories (normal, resolving arteritis, definite arteritis, unsure). (2) A structured reporting template was constructed including pathological category (adventitial, adventitial invasive, concentric bilayer, panarteritis) and presence/absence of features of GCA derived from a literature review. In addition, inflammation in each layer of the vessel wall was categorised as focal, multifocal or diffuse. H&E stained slides from the UK GCA Consortium were scored by a pathologist using this template and Spearman rank test was used to identify features associated with panarteritis, luminal occlusion and peri-arteriolar lymphocytic infiltrates. 12 pathologists took part in the audit. All had been reporting temporal artery biopsies for >5 years using transverse sections +/- longitudinal sections. There was diagnostic consensus on 2 of 9 cases. In the remaining 7 cases, there was lack of agreement about diagnostic category. (2) 250 individual arterial sections from 88 patients in the UK GCA Consortium were scored by 1 pathologist. 207/250 sections showed arteritis. 134/207 sections with arteritis had the fully-developed panarteritis lesion, which was associated with diffuse adventitial inflammation (Table). Luminal occlusion was associated with giant cells, giant cell aggregates, medial destruction, intimal hyperplasia and intimal oedema. Presence / absence of peri-arteriolar lymphocytic infiltrates was not associated with any classical histological feature of GCA. 
Type Of Material Data analysis technique 
Year Produced 2018 
Provided To Others? No  
Impact In view of poor agreement between diagnostic categories, we propose items for a structured (synoptic) temporal artery biopsy report: giant cells, diffuse adventitial inflammation, inflammation in multiple layers of the vessel wall, panarteritis, media destruction, neoangiogenesis, intimal hyperplasia and intimal oedema. Since peri-arteriolar lymphocytic infiltrates or infiltrates around the vasa vasorum were not associated with any classical histological feature of GCA, they may not be specific to the disease and should not be relied on alone for confirmation of histological diagnosis of GCA in clinical practice. We are presenting our findings at Vasculitis 2019 - the 19th International Vasculitis and ANCA workshop. We are collecting biopsy samples and images from the TABUL and UK GCA Consortium studies with a view to extending this work and proving a visual atlas for use as an NHS Pathology training package. 
 
Title Adherence to steroids for management of GCA 
Description Audit of steroid use in Oxford patients with GCA 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? No  
Impact Underway at present 
 
Title BVAS/VDI training database 
Description The new version of the BVAS/VDI training database which we launched in 2018 facilitates training and certification for investigators to become proficient in the evaluation of patients with vasculitis (including giant cell arteritis) 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact The BVAS/VDI training database has been used to support training and certification in disease evaluation in vasculitis for commercial and non commercial studies of vasculitis as well as for clinical training for patients to be evaluated for eligibility to access high cost drugs in accordance with NHS England policies. 
URL https://bvasvdi.ndorms.ox.ac.uk/
 
Title GCAT database 
Description The GCAT registry is a post marketing surveillance registry to explore the effectiveness, safety and prescribing habits of tocilizumab for the treatment of giant cell arteritis in the UK National Health Service. Demographic and core clinical data at the time of enrolment into the Registry is being recorded directly to an on-line database by the investigator or designated member of the research team. We have developed a comprehensive data dictionary for the capture of longitudinal data including laboratory tests and observations, medication, accident and emergency data, comorbidities and disease activity. Follow-up visits for the Registry, conducted every 6 months (+/- 4 weeks) at the time of the patients' routine clinic visits. Outcome data will also be collected, as relevant to the objectives of the Registry, such as relapse, remission, and disease- and treatment-related adverse effects. In addition, all data relevant to fulfilment of NICE guidance for NHS England tocilizumab prescribing will be recorded. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? No  
Impact This project started in April 2019 and only the first 6 monthly report has been delivered so far. The results will be published at the end of the three year project and we will make the data available to others following a suitable embargo period. 
URL https://lida.leeds.ac.uk/target-2/active-research-projects/gcatregistry/
 
Title NIHRBioresource - GCA 
Description National Institute for Health Research (NIHR) Biomedical Research Centres (BRC) are based within the most outstanding NHS and University partnerships in the country, and are leaders in scientific translation. Each BioResource has established groups of healthy volunteers and patients with common or rare diseases who have provided samples (of blood, saliva or other) and agreed to be recalled by genetic make-up (genotype) and/or physical characteristics (phenotype) to participate in medical research and trials. Bringing all this data and resource together will benefit both patients and the public; and researchers in industry, academia and the NHS. Research teams will be able to access large numbers of well characterised individuals. This will particularly help with the study of rare diseases where identifying and recruiting particular groups of volunteers and patients is complicated and can take time. Patients will benefit too, and as the resource grows having larger numbers of people being able to participate in clinical research and trials of new drugs or treatments will enhance that research. Improved access to research volunteers will ensure that research can be completed quickly and effectively, making it easier to bring new treatments to market. The NIHR BioResource is comprised of volunteers from around the country who have given their consent to and a biological sample, they have said we can access their medical notes or health related records, and they are willing to be approached to participate in research studies and trials on the basis of their genotype, and or phenotype. There are 13 NIHR BioResource local centres throughout England. Each centre will recruit people with and without health conditions. Giant cell arteritis (GCA) is a serious form of vasculitis. It disproportionately affects older people, occurring exclusively in those aged over 50 with an average age of onset of 74 years. About 40% of patients experience serious visual manifestations and irreversible ischaemic complications - including blindness - occur in 19% of UK patients. In order to manage the risk of vision loss, patients with suspected GCA are usually treated immediately with high-dose (40-60 mg) glucocorticoids, and they remain on this precautionary treatment until diagnosis is confirmed. Complications arising from this treatment affect up 58-86% of patients and include cardiovascular disease, hypertension, diabetes, fractures and infections, yet only a fifth of suspected cases receive confirmed diagnosis. Prompt diagnosis however, is challenging due to non-specific, varied presentations and lack of a single robust diagnostic biomarker: even a collective of clinical signs and laboratory tests may not prove conclusive. This complex challenge is unique to GCA, yet advances in the field are minimal compared to other diseases of the elderly. We want to collect more information about the condition to help to improve treatment for people with GCA. Patients with giant cell arteritis are also being recruited to the UKGCA Consortium study (UKGCA: to identify genetic and susceptibility determinants of GCA) and the UK and Ireland Vasculitis Rare Disease Group Registry (UKIVAS: a comprehensive database of vasculitis patients in the UK and Ireland). Our aspiration is that patients will be recruited to the UKGCA Consortium, and ideally UKIVAS, alongside the NIHR BioResource - Rare Diseases study. This will allow the rich phenotypic and molecular data available from these studies to be exploited. Inclusion: All patients with a clinical diagnosis of giant cell arteritis made within secondary medical care in the UK and willing and able to provide informed consent. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? No  
Impact This resource has only just been established and we will provide an update in our next report. 
URL https://bioresource.nihr.ac.uk/wp-content/uploads/2019/08/Web-summary-GCA-v1-05082019.pdf
 
Title NIHRBioresource - Vasculitis 
Description National Institute for Health Research (NIHR) Biomedical Research Centres (BRC) are based within the most outstanding NHS and University partnerships in the country, and are leaders in scientific translation. Each BioResource has established groups of healthy volunteers and patients with common or rare diseases who have provided samples (of blood, saliva or other) and agreed to be recalled by genetic make-up (genotype) and/or physical characteristics (phenotype) to participate in medical research and trials. Bringing all this data and resource together will benefit both patients and the public; and researchers in industry, academia and the NHS. Research teams will be able to access large numbers of well characterised individuals. This will particularly help with the study of rare diseases where identifying and recruiting particular groups of volunteers and patients is complicated and can take time. Patients will benefit too, and as the resource grows having larger numbers of people being able to participate in clinical research and trials of new drugs or treatments will enhance that research. Improved access to research volunteers will ensure that research can be completed quickly and effectively, making it easier to bring new treatments to market. The NIHR BioResource is comprised of volunteers from around the country who have given their consent to and a biological sample, they have said we can access their medical notes or health related records, and they are willing to be approached to participate in research studies and trials on the basis of their genotype, and or phenotype. There are 13 NIHR BioResource local centres throughout England. Each centre will recruit people with and without health conditions. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact This resource has only just been approved. We will provide an update in our next report. 
 
Title PROTEA 
Description Prospective data collection for new GCA 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? No  
Impact Just starting 
 
Title Research Tissue Bank 
Description The samples collected for this Research Tissue Bank will be predominantly derived from projects associated with Professor Ann Morgan's TARGET Consortium. The Research Tissue Bank may also be used to store tissue derived from other projects within Ann's programme of research including those from patients (and controls) with inflammatory arthritis, polymyalgia rheumatica (PMR) and other vasculitides, such as Behçet's syndrome, which are important disease controls for the proposed biomarker projects. Samples collected for the UKGCA Consortium Clinical and immunogenetic characterization of GCA and PMR. GCA is a disease of the elderly. It is very rare to find GCA in people aged under 50 years, and the average age of onset is 72 years. Women are more likely to develop GCA compared to males, but we are obtaining samples from male and female patients. In the GCA Consortium work stream, we collect blood and temporal artery biopsies from all (consenting) patients with suspected GCA. We currently have 1,250 samples (1210 retrospective and 40 prospective) in this collection and have 45 centres from around the UK who are continuing to actively collect samples. Samples collected for ADDRESS-PMR The use of ultrasound to improve diagnosis in patients referred with suspected polymyalgia rheumatica. PMR is an inflammatory musculoskeletal disease that overlaps with GCA and affects older people (typically aged >50 years) and more often women than men. PMR is usually diagnosed and treated in primary care with glucocorticoids. In ADDRESS-PMR we are collecting blood samples from 205 male and female patients (all over the age of 40 years) with suspected PMR over a two-year period at five different time points. The study closed to recruitment in May 2017 and last patient last visit is expected in January 2019. A subset of these patients have subsequently developed both GCA and rheumatoid arthritis. Samples collected for - Functional characterization of the genes and proteins involved in the development and severity of autoimmune and (auto) inflammatory diseases. Functional characterisation of the genes and proteins involved in the development and severity of autoimmune and (auto) inflammatory diseases. Functional Families covers a range of sub-studies with the common aim to functionally characterise various genes shown to be associated with a range of autoimmune and (auto) inflammatory diseases. Each sub-study can collect blood and/or synovial fluid samples from male and female patients (aged 18 years and above) with inflammatory diseases, and from healthy/inflammatory disease controls. Samples collected for the EYEPATIENT (Elderly Controls) - Substudy of Functional characterization of the genes and proteins involved in the development and severity of autoimmune and (auto) inflammatory diseases. The aim of this sub-study was to collect samples from older patients without active inflammatory disease, in order to study disease mechanisms and validate diagnostic biomarkers for age-related inflammatory diseases (such as GCA, PMR, vasculitis and other rheumatic diseases). 39 blood samples were collected from older patients (aged 50 years and above) who attended the cataract pre-assessment clinic in 2015. Samples collected for the Biomarker Behçet's Study Behçet's disease (BD) is a systemic inflammatory vasculitis in which patients experience recurrent episodes of acute inflammation in the blood vessels and tissues. It is a very rare disease in the UK. The symptoms of BD may be treated with corticosteroids, immunosuppressants and biological therapies but there is no cure. The aim of this study was to investigate the specificity of novel candidate biomarkers for Behçet's disease by comparing with serum from patients with other vasculitides and inflammatory diseases. Blood samples were collected cross-sectionally from patients with Behçet's disease, with a repeat sample taken at the time of subsequent flare. 67 patients (aged 18 years and above) were recruited between 2007 and 2015. Samples collected for STAY-ACTIV Assessment of the muscular, vascular and endocrine effects of glucocorticoid therapy in inflammatory diseases. STAY-ACTIV is a feasibility study aiming to improve methods of assessment for steroid-related health effects. The initial cross-sectional arm was completed in 2016, recruiting healthy participants and those with inflammatory or autoimmune disease (some of whom were receiving steroid therapy). In this study arm, blood samples, urine samples, muscle biopsies and skin biopsies were collected if the patient consented to the specific sample being obtained. 43 males and female patients aged 40 years and above were recruited in total. The longitudinal arm is currently suspended to recruitment but has collected blood and urine samples and some muscle biopsies from 12 participants at two further visits. Samples collected for FACT Managing Fatigue with physical ACTivity monitors. FACT was an interventional study with the aim of identifying whether a physical activity monitory and a walking regime would help motivate patients to increase the number of daily steps taken, and secondly whether this would help improve fatigue symptoms, when combined with a slow steroid reduction regime. Blood samples were taken from 13 patients (males and female aged 40 years and above) who were recruited in 2016-17 In addition to this current portfolio of research, we are investigating new opportunities and anticipate that these will involve the collection of whole blood, plasma, serum, saliva, urine, temporal artery, skin and muscle biopsies. We only plan to collect human samples, and will not deposit samples from anyone under the age of 18 years. We are working with the Leeds MRC Medical Bioinformatics Centre to develop a informatics resource to serve TARGET's requirements, thereby eliminating the need for hard-to-access data and tissue silos. We will include a wealth of resources including a database of samples. This data will be fully anonymised, but will include generic descriptions related to sample type, patient group, age, sex and disease status. All data related to the project will be held at the MRC Medical Bioinformatics Centre. This Centre provides a secure data handling through the Integrated Research Campus (IRC). IRC processes are based on international standards and legal requirements for the confidentiality, availability and integrity of data. Processes are determined by the IRC's Information Security Management System (ISMS) for which the IRC has ISO 27001 and HSCIC IGT Level 2 accreditation. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? No  
Impact Our Research Tissue Bank is awaiting approval. We will provide details of our first year progress in our next report. All members of TARGET will have access to our samples at the basic cost of preparation and delivery only. Any new parties would also 'cost-covered' access to these samples. In addition to these Partners, numerous members of other Institutes have pledged their support for the collective aims of the TARGET Consortium. These institutes, along with any other non-academic/NHS organisations would cover the full cost of the preparation and delivery for each sample, plus a 10% fee. We will welcome opportunities for external parties to acquire our surplus RTB samples. There will be an adjusted pricing structure for commercial requests which will be based on a competitive model provided by other suppliers. We will advertise the RTB through our dedicated TARGET webpage (hosted through the Leeds Institute for Data Analytics) and further promotion will take place at local and international conference, meetings and networking events. We will actively promote our RTB, and interested parties will be able to view the available stocks through a search facility provided as part of the TARGET Informatics and Research Tissue Bank Platform. The MRC TARGET Partnership has a Partnership Management Board in relation to the whole Partnership. The Chair of the Partnership Management Board is Professor Ann Morgan and the Vice-chair is Professor Raashid Luqmani (University of Oxford). Various other Partners will have additional roles on this board. The Partnership Management Board will meet every month to discuss TARGET activity including any request for samples from the Research Tissue Bank. Access to the TARGET RTB samples will be made on an application only basis. There will be a seven step application process for access to TARGET RTB samples. This process will remain the same for all parties regardless of their relationship to the TARGET Partnership or TARGET Consortium. 1) Search for samples. Interested parties will use an online sample finder to search for samples that match their criteria. The sample finder will be hosted through the TARGET Informatics and Research Tissue Bank Platform. 2) Register an account. Anyone wishing to apply for samples will need to create an account with us. Details we require from account holders will include: name, job title, business name and address, email, telephone number. This will expedite multiple applications, and deter speculative approaches. Once the appropriate samples have been identified, applicants will be asked to complete a standardised application form . We have also produced an applicant guidance document to help people with their applications . 3) Review and submit. If co applicants are listed, they must have reviewed all the information in the application before submission. 4) TARGET Partnership check. Applications will be checked for missing information by a member of the TARGET team. We will decide on the level of review required by asking the following. Does the application deplete the Bank's stock? Is the project already peer-reviewed by an external funder or equivalent? 5) Review Committee review of sample request. A light-touch review will conducted by the Executive Committee and if a more detailed review is needed then a Specialist Group Review will be convened. 6) Decision. We aim to provide an outcome within four weeks of submission. 7) Samples released. Samples will be dispatched once a Material Transfer Agreement has been agreed. 
 
Title Scoring system of temporal artery biopsy samples to diagnose GCA 
Description Temporal artery biopsy (TAB) may be considered gold standard for Giant Cell Arteritis (GCA) diagnosis but there is debate over how accurately a clear diagnosis can be made1. No studies have assessed how different pathologists score the same sample. There was therefore an unmet need to conduct a nationwide clinical audit to determine if experienced pathologists were in agreement in the diagnosis of GCA, with the ultimate aim of standardising and streamlining criteria for GCA diagnosis. The audit was conducted in June - July 2018. Single images were shown using Google forms. Respondents had a choice of fixed answers related to diagnosis (normal, resolving arteritis, definitive arteritis, unsure) and a free text box allowing elaboration. The audit results were used to construct a scoring system which modified the systems of Chatelain and Nordborg2,3 and the four category classification of Hernandez-Rodriguez et al4. Digital images of 88 biopsies and 250 individual arterial sections from the UK GCA consortium were scored: 207 showed GCA and these were analysed. A GCA atlas, which captures the wide spectrum of histological features encountered in the diagnosis of GCA, was constructed. The audit had 12 respondents: 11 answered most of the questions, and 10 completed the audit in full. Respondents were Consultant Pathologists, who had routinely reported TAB for over five years. The majority reported using transverse sections. Agreement on diagnosis was reached in two/nine cases. In the remaining seven cases, the range of answers varied extensively. Scoring of GCA sections confirmed the presence of distinct patterns: adventitia only (A), adventitia invasive (AI), concentric bilayer (CB) and pan-arteritis (PA). A and AI were usually focal, whilst CB and PA were diffuse. PA was more likely to show vascular occlusion, association with giant cells, destruction of media and neoangiogenesis. Luminal occlusion tended to be associated with giant cells, media destruction, intimal hyperplasia and intimal oedema. Periarteriolar lymphocytic infiltration (PALI) was not associated with any features of GCA. We suggest a structured reporting template, and the use of a GCA atlas as an educational tool and reference resource. We will expand the number of cases for scoring, and correlate the histological features with cell subsets, RNA, protein and metabolic biomarkers. 
Type Of Material Data analysis technique 
Year Produced 2018 
Provided To Others? No  
Impact The results of this project were presented at the TARGET Annual Scientific Meeting in October 2018. A poster presentation has been accepted at the 19th International Vasculitis & ANCA Workshop, and the British Society for Rheumatology meeting Birmingham. It has also been submitted as a letter to Rheumatology. We will expand the audit and develop an educational resource for pathologists nationwide. 
 
Title Service evaluation of the diagnosis and treatment of giant cell arteritis using the NETIMIS model 
Description This model will map the flow of patients with suspected GCA through the current LTHT pathway by looking at the associated event data on various systems within the Patient Management Service (PMS) database. We will evaluate these events in comparison with the preferred treatment pathway, and make suggestions for improvement to LTHT care for GCA. This will be the first of its kind to model current clinical care pathways for GCA. The cohort of interest will be identified through the PMS database. We will need the date and time that various events in the care pathway occurred in order to build a comprehensive patient flow tool. We have submitted an application (January 2018) to the Leeds Data Warehouse Service for access to the data we require. We will use this tool to explore potential deviations from the 'usual' clinical process, and to model any changes to the process. In order to provide a comprehensive service evaluation, the following events in the care pathway have been requested: inpatient admissions; outpatient appointments; patient transfers to different departments within the LTHT; blood tests; TABs; retinal examinations; radiology examinations; diagnostic outcomes (including pathology results); prescriptions; medical complications. NETIMIS is a commercial care pathway simulation tool that has already successfully modelled pathways in other settings. 
Type Of Material Computer model/algorithm 
Year Produced 2018 
Provided To Others? No  
Impact This modelling work is in progress and notable findings will be provided in our next report. 
 
Title Steroid audit 
Description Steroid adherence data collected as part of the audit conducted at the University of Oxford (audit of glucocorticoid prescription in patients with GCA). 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? No  
Impact We were planning to use this to correct the estimations of GC toxicity by applying evidence-based scenarios of treatment adherence in sensitivity analyses. 
 
Title TARGET Informatics Platform 
Description We capitalise on MRC investment in the Leeds MRC Medical Bioinformatics Centre to build a common resource platform for data that can be accessed by all TARGET partners. We have developed strategies for evaluating novel diagnostics and tools for assessing the extent of vascular inflammation that may also be useful for monitoring. Identification & validation of biomarkers (DNA, RNA, protein, from blood or tissue and imaging,) that predict future visual loss/stroke is a priority area of investigation. Detailed epidemiological analyses of large contemporary datasets will ensure robust and accurate estimations of effect size for any intervention and determine appropriate sample size and primary/ secondary outcome measures for future clinical trials. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? No  
Impact Our Informatics Platform is in progress. It is being built with support from Adam Keeley (Senior Analysis, Leeds Institute of Data Analytics) and leadership from Barry Haynes. Before clinical data can be compiled, we are comparing the proformas and coding schedules currently in use to assess whether these cover domains of relevance for all clinical specialities. A full audit of existing data resources within the Partnership (including metadata, such as consent) mapped to a common semantic model is providing the basis for sharing existing resources. We are in the process of aligning our extant collections and new prospective studies on a common informatics platform. The MRC Centre will provide secure access to a trusted research environment with HPC and storage, software and processing facilities that will remain fully compliant with current and emerging European and UK data protection requirements and will include tools for collaborative bioinformatics research, such as tranSMART. This will enhance the power of individual cohorts to address hypothesis-driven analyses and allow cross-disease collaborations (including other MRC Consortia). Careful review of ethical approval, governance and prior data-sharing agreements will be undertaken for all studies. All data will be de-identified, with different levels of access appropriate to the patient's consent, regulatory approval, data sharing and collaboration agreements. We do not under-estimate the challenges of data linkage, cleansing e-health records and analysis of large molecular data-sets. Through collaboration with other MRC Centres we will work to overcome these hurdles. We will develop a solution for future extensions, e.g. linkage to additional primary care, secondary care and imaging (ultrasound, MRI and PET-CT) data. Initial datasets from the TARGET BIOMARKERS study will be uploaded to support LIDA Data Intern projects. This will include clinical data from UKGCA Consortium (Leeds), TABUL (Oxford), ADDRESS-PMR (Leeds) with RNASeq data generated on the SJUH Campus, metabolomics data generated at the University of Birmingham and protein biomarker generated by Myriad diagnostics (Industry partner). We have had discussions with NHS Digital about linkage of data between UKGCA and HES, with the outcome being we will need to re-consent patients for linkage. We have validated NHS number entries within UKGCA to ensure that high quality linkage. 
 
Title UK GCA Consortium Registry 
Description The aim of this study is to find genetic determinants of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) susceptibility in order to yield novel insights into disease pathogenesis. There are six different work streams: 1) Phenotype: characterising GCA and PMR subtypes, based on clinical features and research tests, 2) Life Impact: determining what aspects of the disease and treatment affect quality of life, 3) Long-term Outcome: characterising the prognosis of GCA and PMR - both effects of the disease and its treatment, 4) Exploratory: exploring the potential role of environmental factors and co-morbidities on phenotype and outcomes, 5) Diagnosis, Prognosis (prospective study): improving the diagnosis of GCA and PMR, and identifying factors that will predict prognosis, 6) Disease Activity ("flares" sub-study): finding a better biomarker for GCA and PMR disease activity, optimising steroid dose for individual patients. Data included in this database includes: Clinical: diagnosis (features and manifestations, diagnostic tests), co-morbidities, smoking and alcohol history, steroid treatment, flares, drug history, adverse events, family history. Environmental: diet and sunlight, periodontal and autonomic function questionnaires. Demographic: race, English indices of deprivation derived from post code. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? No  
Impact This database is in progress we aim to use this database to: 1) provide clinical characterisation of GCA and PMR cohorts (compared to controls) and allow correlation of relevant clinical features with cells and molecules (including DNA and RNA) in body fluids and/or in the arterial and periarterial tissue, 2) conduct genetic studies on this cohort, investigating the contribution of relevant genes to susceptibility to GCA/PMR and the risk of ischaemic complications and response to therapy. 3) assess study samples of the tissue affected by GCA (the temporal artery), 4) perform functional studies of the GCA and PMR-associated polymorphisms, and 5) analyse autoantibodies and cells/molecules in body fluids from patients with GCA and PMR. 
 
Title UKIVAS (UK and Ireland Vasculitis Registry) database 
Description The UKIVAS database is designed to collect registry information about all forms of vasculitis. It has been evolving over time to widen the use for more detailed evaluation of some forms of vasculitis. The database is endorsed by NHS England policy on use of high cost drugs for some forms of vasculitis 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact The database will be used for data collection in the GCAT registry of patients (giant cell arteritis starting therapy with tocilizumab) 
URL https://research.ndorms.ox.ac.uk/ukivas/
 
Description Access to PET-CT images from the UK GCA Consortium 
Organisation Alliance Medical
Country United Kingdom 
Sector Private 
PI Contribution The UK Giant Cell Arteritis (UKGCA) Consortium (https://lida.leeds.ac.uk/target-2/active-research-projects/gcatregistry/uk-gca-consortium/) is a national registry of patients with giant cell arteritis - a form of large vessel vasculitis and is led by Prof Ann Morgan at University of Leeds. As part of this consortium a local study is being conducted at University of Leeds with Professor Andrew Scarsbrook evaluating FDG PET-CT scans undertaken as part of routine patient management. The aim of the study is to look at more sophisticated analysis of imaging modalities (artificial intelligence (AI) or radiomics) in this rare condition to see if it is possible to more accurately diagnose alternative forms of large vessel vasculitis from atherosclerosis, and to predict which patients are at higher risk of vascular complications ,such as aneurysm formation or stenosis. There are a number of patients around the country who have consented to their imaging data being used via the UKGCA consortium and we believe that many of them may have had PET-CT scans performed at Alliance Medical scanning sites. Rheumatology colleagues at these centres have been contacted and are amenable to sharing details of consented patients who have had imaging studies, so that a larger dataset can be collated in order to develop and test an AI algorithm. We have been given permission to access the scans of UKGCA consented patients who have undergone PET-CT and have data stored on AML servers. We propose accessing the imaging data via one of the IntelliRad workstations in the Nuclear Medicine Department in Leeds. Any data exported would be fully anonymised and used to train a neural network/deep learning model. Patient demographic data and outcomes are held in the UK GCA consortium database which is held at University of Leeds.
Collaborator Contribution Alliance will facilitate transfer of anonymised PET-CT scans for patients enrolled in the UKGCA consortium who have consented for linkage.The following centres have recruited patients to the UKGCA and align with AML scanning sites: - Newcastle (Freeman Hospital)- 79 patients recruited - Birmingham (Queen Elizabeth Hospital) - 8 patients recruited - Cambridge (Addenbrookes Hospital) - 59 patients recruited - Truro (Royal Cornwall Hospital) - 27 patients recruited - Basildon: 25 patients - Northampton: 69 patients - Norfolk and Norwich: 78 patients
Impact We have already tested our systems using data from 20 patients of the Leeds Teaching Hospitals NHS Trust. There are no other outputs to report as we have been developing the governance processes and have not yet received any data. We will provide outputs in our next submission.
Start Year 2019
 
Description BIOVAS Project 
Organisation UK and Ireland Vasculitis Rare Disease Group
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Professors Ann Morgan, Raashid Luqmani, Justin Mason and David Jayne have been working in collaboration with UKIVAS (the UK and Ireland Vasculitis Group) and Vasculitis UK to develop a clinical trial for rare vasculitides that do not have a biologic approved for routine clinical use. This project is led by Professor Jayne who was recently awarded a Health Technology Assessment Programme for a study entitled 'Biologics in refractory vasculitis (BIOVAS): A pragmatic, randomised, double-blind, placebo-controlled, modified-crossover trial of biologic therapy for refractory vasculitis in children and adults'. The BIOVAS study will explore three different biologics - infliximab, tocilizumab and rituximab - chosen for scientific reasons and because there is already some experience of their use in vasculitis. The aim is to recruit 140 patients (children and adults) with refractory vasculitis and compare each drug to a placebo treatment. Patients will have the following types of vasculitis: giant cell arteritis, Takayasu's arteritis, polyarteritis nodosa, cerebral vasculitis, Cogan's syndrome, relapsing polychondritis, IgA vasculitis, non-infective cryoglobulinaemic vasculitis. This application is in response to a commissioned call to test whether biologics used for rare autoimmune conditions are cost-effective.
Collaborator Contribution All collaborators in this grant have made significant contributions to the development and submission of this clinical trial application. Each collaborator will make a unique and important contribution to the delivery of the project and any publications which may arise. The project will be led by Professor David Jayne (University of Cambridge) and multiple members of the TARGET Partnership are co-applicants on this grant.
Impact No outcomes to report yet other than the award of the grant application to the NIHR Health Technology Assessment Programme.
Start Year 2017
 
Description Commissioning of Tocilizumab for Giant cell Arteritis in the NHS 
Organisation NHS England
Country United Kingdom 
Sector Public 
PI Contribution Several members of the TARGET Partnership contributed to the recent NICE appraisal for the commissioning of Tocilizumab in GCA. A larger group of TARGET Partners worked closely with the British Society of Rheumatology (BSR), British Society of Ophthalmology (BSO) and the patient groups Vasculitis UK and PMRGCAuk to lodge an appeal to the draft appraisal.
Collaborator Contribution Contribution to individual, TARGET, BSR and BSO responses to the draft NICE consultation Jan 2018. In addition a preliminary application to NHS England for additional research into the use of Tocilizumab into GCA was submitted by Dr Bridget Griffiths (CRG lead) and Professor Ann Morgan on behalf of TARGET. This clinical trial was not developed further once NICE published their final appraisal in March 2018. TARGET partners have worked with professional bodies to support implementation of tocilizumab within the NHS and the creation of a registry to support post marketing surveillance
Impact The outcome of the appeal to the preliminary assessment that tocilizumab should not be commissioned for use in giant cell arteritis in the UK was positive. The TARGET team contributed to the development of the NHS England definitions of relapsing and refractory disease and in disseminating best practice within the NHS. This work has directly led to the development of a Registry for tocilizumab-treated GCA patients, which was recently funded by Roche pharmaceuticals.
Start Year 2019
 
Description Dissecting the role of multinucleated giant cells in the pathogenesis of GCA 
Organisation Massachusetts General Hospital
Country United States 
Sector Hospitals 
PI Contribution This collaboration involved the following: Gary Reynolds (Clinical Lecturer, Newcastle University); Daniel Maunder (PhD Student, Newcastle University); Muzlifah Haniffa (Wellcome Senior Clinical Fellow, Newcastle University); John Isaacs (Professor of Clinical Rheumatology, Newcastle University); Ann Morgan (Professor of Molecular Rheumatology, Leeds University); Alexandra-Chloe Villani (Director of the Single Cell Genomics Program, Massachusetts General Hospital). Ann Morgan revised the research proposal, provided intellectual input and is the external Sponsor.
Collaborator Contribution Collaboration/Partnership 1: Gary Reynolds designed experiments to develop preliminary data to support an application for a Wellcome Trust Clinical Research Career Development Fellowship (for GR). Gary Reynolds and Daniel Maunder performed experiments and analysed data. Gary Reynolds wrote the research proposal. Muzlifah Haniffa, John Isaacs and Alexandra-Chloe Villani revised the research proposal and provided intellectual input.
Impact This collaboration led to Gary Reynolds' Clinical Research Career Development Fellowship award. Further outcomes will be reported as the collaboration progresses.
Start Year 2018
 
Description Dissecting the role of multinucleated giant cells in the pathogenesis of GCA 
Organisation Newcastle University
Country United Kingdom 
Sector Academic/University 
PI Contribution This collaboration involved the following: Gary Reynolds (Clinical Lecturer, Newcastle University); Daniel Maunder (PhD Student, Newcastle University); Muzlifah Haniffa (Wellcome Senior Clinical Fellow, Newcastle University); John Isaacs (Professor of Clinical Rheumatology, Newcastle University); Ann Morgan (Professor of Molecular Rheumatology, Leeds University); Alexandra-Chloe Villani (Director of the Single Cell Genomics Program, Massachusetts General Hospital). Ann Morgan revised the research proposal, provided intellectual input and is the external Sponsor.
Collaborator Contribution Collaboration/Partnership 1: Gary Reynolds designed experiments to develop preliminary data to support an application for a Wellcome Trust Clinical Research Career Development Fellowship (for GR). Gary Reynolds and Daniel Maunder performed experiments and analysed data. Gary Reynolds wrote the research proposal. Muzlifah Haniffa, John Isaacs and Alexandra-Chloe Villani revised the research proposal and provided intellectual input.
Impact This collaboration led to Gary Reynolds' Clinical Research Career Development Fellowship award. Further outcomes will be reported as the collaboration progresses.
Start Year 2018
 
Description GCA PROM Development 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution Professor Richard Watts (Consultant Rheumatologist, University of Cambridge) has collaborated to develop Patient Reported Outcome Measures (PROMs) for GCA in order to assess health related quality of life in relation to GCA and its treatment, and for use as an outcome measure in clinical studies.
Collaborator Contribution Jo Robson (Consultant Rheumatologist, University West of England) collaborated on this project to develop a GCA-specific PROM which will accurately and reliably measure whether GCA patients' symptoms and health-related quality of life are changed by new medications.
Impact The development of a new PROM requires the use of mixed methods applied in three distinct phases: Phase 1 - The collection and analysis of qualitative data to inform PROM candidate questions, with additional refinement via cognitive debriefing: Phase 2 - item reduction and determination of underlying PROM scale structure and cross-sectional measurement properties; Phase 3 -longitudinal and comparative analysis/verification of the new PROM's measurement properties. Phases 2 and 3 involve using quantitative methods within the context of a longitudinal survey. This study is concerned with the first qualitative study (Phase 1). Results from this study will inform and underpin the more quantitative phases 2 and 3, and highlight the impact on patients of having GCA.
Start Year 2019
 
Description GCA PROM Development 
Organisation University of the West of England
Country United Kingdom 
Sector Academic/University 
PI Contribution Professor Richard Watts (Consultant Rheumatologist, University of Cambridge) has collaborated to develop Patient Reported Outcome Measures (PROMs) for GCA in order to assess health related quality of life in relation to GCA and its treatment, and for use as an outcome measure in clinical studies.
Collaborator Contribution Jo Robson (Consultant Rheumatologist, University West of England) collaborated on this project to develop a GCA-specific PROM which will accurately and reliably measure whether GCA patients' symptoms and health-related quality of life are changed by new medications.
Impact The development of a new PROM requires the use of mixed methods applied in three distinct phases: Phase 1 - The collection and analysis of qualitative data to inform PROM candidate questions, with additional refinement via cognitive debriefing: Phase 2 - item reduction and determination of underlying PROM scale structure and cross-sectional measurement properties; Phase 3 -longitudinal and comparative analysis/verification of the new PROM's measurement properties. Phases 2 and 3 involve using quantitative methods within the context of a longitudinal survey. This study is concerned with the first qualitative study (Phase 1). Results from this study will inform and underpin the more quantitative phases 2 and 3, and highlight the impact on patients of having GCA.
Start Year 2019
 
Description GCA research programme with Kiniksa Pharmaceuticals 
Organisation KINIKSA PHARMACEUTICALS (UK), LTD
Country United Kingdom 
Sector Private 
PI Contribution We have signed a CDA with Kiniksa Pharmaceuticals in order to have access to their market research on GCA and to discuss a potential business relationship with Kiniksa in connection with giant cell arteritis, PMR and glucocorticoid toxicity.
Collaborator Contribution Kiniksa have expressed an interest in working with us on a variety of projects in the GCA pipeline. They have expressed an interest in making a financial contribution to our 2019 Scientific Conference. Kiniksa have developed a monoclonal antibody inhibitor of GM-CSF signalling and are currently enrolling a global Phase 2 study in GCA.
Impact This partnership is at an early stage: we signed the CDA in February 2019.
Start Year 2018
 
Description Genome-wide association studies utilising the UK GCA Consortium cohort 
Organisation Spanish National Research Council (CSIC)
Department State Agency Superior Council for Scientific Research
Country Spain 
Sector Public 
PI Contribution We are genotyping samples taken from the UK GCA Consortium (UK GCA). The original purpose of this observational study was to find genetic determinants of GCA susceptibility in order to yield novel insights into disease pathogenesis. To date, over 1,900 patients with suspected or clinically diagnosed GCA have been recruited from 44 primary and secondary care centres in England and Wales. In addition to clinical data, patients are asked to provide explicit consent for genetic (whole-genome) analysis of blood samples. Data is compiled in a central database, and samples are collected from all sites and stored in HTA licensed premises in the School of Medicine (University of Leeds, UK).
Collaborator Contribution De-identified samples collected from this study will be shared with Professor Javier Martin, Grenada, Spain with whom several UK-Spanish genetic studies are being planned through the EU HELICAL ITN, supported by 3 PhD students (2 Leeds (MRC and EU-funded) and 1 Granada (EU-funded)).
Impact This has been a productive collaboration, where a number of genetics studies have been undertaken and published. We are currently expanding our cohort sizes with each of our 3 PhD students planning to use the resultant genetic and phenotypic data to explore different traits from conventional GWAS studies through to assessment of polygenic risk scores, pQTL and eQTL analyses.
Start Year 2018
 
Description Institute for Risk and Uncertainty 
Organisation University of Liverpool
Country United Kingdom 
Sector Academic/University 
PI Contribution Developing methods and software for diagnosing GCA and PMR
Collaborator Contribution Reumuntiabo provided clinical data for algorithm testing
Impact Papers, posters, presentations, software (disciplines includes, computer science, risk and uncertainty, mathematics and statistics.
Start Year 2018
 
Description Javier Martín - genome-wide association studies 
Organisation Spanish National Research Council (CSIC)
Department Institute of Parasitology and Biomedicine Lopez-Neyra
Country Spain 
Sector Public 
PI Contribution We have undertaken a number of large scale genetic studies with this group. We have performed the first international immunochip and genome-wide association study and have recently completed a pan-vasculitis study. Our future studies will explore different patient subgroups and clinical outcomes. We are in the process of sending over 500 DNA samples (extracted from whole blood) from patients with a clinical diagnosis of GCA (collected under the ethical approval for the UKGCA Consortium and TABUL studies) to this collaborator. for genotyping. Professor Jenny Barrett (Leeds Institute of Cancer and Pathology, University of Leeds) will lead the analysis of this data from Leeds, and will liaise with the team in Grenada to ensure quality control.
Collaborator Contribution Professor Javier Martín Ibáñez and his team will genotype these samples using a genome-wide chip and we will collaboratively analyse any data arising from this work. All labour and laboratory consumables will be provided at no cost to TARGET.
Impact We have published our genome-wide and pan vasculitis studies. The collaboration to analyse predictors of different clinical subgroups and outcomes is at an early stage and we are in the process of gathering appropriate samples. A material transfer agreement is in place. With the award of HELICAL we have appointed two ESRs to deliver on this research project.
Start Year 2017
 
Description Maria Cid - pathogenic pathways 
Organisation University of Barcelona
Country Spain 
Sector Academic/University 
PI Contribution We are exploring the pathogenic pathways involved in GCA, including isolation of vascular smooth muscle cells from freshly-isolated temporal artery biopsies, co-culture systems and culture of gender-matched temporal artery biopsies in 3D matrix. Using this allows model changes in transcripts, proteins and activation/inactivation of signalling pathways after intervention to be explored. Additional end-points that can be investigated in this system are changes in specific cell subsets (Th1, Th2 and Treg subsets), apoptosis, proliferation and migration of myointimal cells.
Collaborator Contribution Dr Cid, will conduct functional models to explore pathogenic pathways and undertake tissue morphometry.
Impact This collaboration is in development and we are currently discussing study design and the availability of appropriate samples. A progress update will be provided in the next report. This project was included in a successful Horizon2020 ITN application, named HELICAL. We are currently in the process of recruiting a early stage researcher to undertake the research project.
Start Year 2017
 
Description NETIMIS - health care pathway mapping as part of a service evaluation for giant cell arteritis within the Leeds Teaching Hospitals NHS Trust 
Organisation University of Leeds
Department Leeds Institute of Data Analysis
Country United Kingdom 
Sector Academic/University 
PI Contribution The aim of this project is to map the flow of patients with suspected giant cell arteritis (GCA) through Leeds Teaching Hospital Trust (LTHT) by exploring and recording activity data on various systems. We are jointly conducting an empirical investigation (involving systematic interviews with NHS Consultants) detailed reviews of patient records, and coding within the Patient Pathway Manager (PPM), to capture business processes within the NHS using standard process analytics methods (e.g. SQIRO, data mining) to create models and simulations of current care pathways for patients with suspected GCA. Once the current pathway models have been created, a set of 'to-be' and future state redesign models will be created, as a means of identifying potential changes for improvement, and to provide confirmation of processes that work effectively. For example, a comparison of the current standard of care with the potential cost reductions and improved outcomes that might be obtained by implementing a fast-track clinic model. The PI of this grant (Professor Ann Morgan) is leading this project alongside Dr Charlotte Harden (the Programme Manager for this grant) and Dr Sarah Mackie (Consultant Rheumatologist and Associate Professor). Prof Ann Morgan and Dr Sarah Mackie will facilitate access to LTHT and clinical staff, provide clinical and research insights, and support process improvement and dissemination.
Collaborator Contribution The pathways will be modelled using NETIMIS, a commercial care pathway simulation developed by X-Lab. This service is being provided in kind. Expert technical support is being provided by the Company Director of X-Lab, Owen Johnson. Owen is providing the student that is working on this project with full training and on-going support. He is attending monthly progress meetings in person and is fully engaged in the development of this project. Owen will help with the refinement of the model and any publications which may arise from this collaboration. X-Lab will assist with client liaison, office accommodation and expenses such as travel. The modelling aspect of the project will be conducted by Sahar Salimi-Avval-Bejestani as part of her final undergraduate project. Sahar has already delivered models using this tool for other NHS projects.
Impact This project will make a major contribution to the understanding and improvement of GCA pathways within LTHT. It will be informative to both clinicians and academics in the field, and could be used to assist NHS pathway improvement. We will jointly produce at produce at least one case study for publication and the student will be asked deliver presentations at TARGET Consortium Partnership Management Board Meetings.
Start Year 2017
 
Description NETIMIS - health care pathway mapping as part of a service evaluation for giant cell arteritis within the Leeds Teaching Hospitals NHS Trust 
Organisation X-Lab Ltd.
Country United Kingdom 
Sector Private 
PI Contribution The aim of this project is to map the flow of patients with suspected giant cell arteritis (GCA) through Leeds Teaching Hospital Trust (LTHT) by exploring and recording activity data on various systems. We are jointly conducting an empirical investigation (involving systematic interviews with NHS Consultants) detailed reviews of patient records, and coding within the Patient Pathway Manager (PPM), to capture business processes within the NHS using standard process analytics methods (e.g. SQIRO, data mining) to create models and simulations of current care pathways for patients with suspected GCA. Once the current pathway models have been created, a set of 'to-be' and future state redesign models will be created, as a means of identifying potential changes for improvement, and to provide confirmation of processes that work effectively. For example, a comparison of the current standard of care with the potential cost reductions and improved outcomes that might be obtained by implementing a fast-track clinic model. The PI of this grant (Professor Ann Morgan) is leading this project alongside Dr Charlotte Harden (the Programme Manager for this grant) and Dr Sarah Mackie (Consultant Rheumatologist and Associate Professor). Prof Ann Morgan and Dr Sarah Mackie will facilitate access to LTHT and clinical staff, provide clinical and research insights, and support process improvement and dissemination.
Collaborator Contribution The pathways will be modelled using NETIMIS, a commercial care pathway simulation developed by X-Lab. This service is being provided in kind. Expert technical support is being provided by the Company Director of X-Lab, Owen Johnson. Owen is providing the student that is working on this project with full training and on-going support. He is attending monthly progress meetings in person and is fully engaged in the development of this project. Owen will help with the refinement of the model and any publications which may arise from this collaboration. X-Lab will assist with client liaison, office accommodation and expenses such as travel. The modelling aspect of the project will be conducted by Sahar Salimi-Avval-Bejestani as part of her final undergraduate project. Sahar has already delivered models using this tool for other NHS projects.
Impact This project will make a major contribution to the understanding and improvement of GCA pathways within LTHT. It will be informative to both clinicians and academics in the field, and could be used to assist NHS pathway improvement. We will jointly produce at produce at least one case study for publication and the student will be asked deliver presentations at TARGET Consortium Partnership Management Board Meetings.
Start Year 2017
 
Description Neutrophils in vasculitis 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution Creating research protocols, providing detailed clinical phenotyping of selected cases for research; we are proposing to adapt this study to some of the research questions in TARGET
Collaborator Contribution Co-applicants on grants to research bodies
Impact N/A
Start Year 2017
 
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 Olink - preliminary proteomic analysis of plasma samples taken from patients with polymyalgia rheumatica 
Organisation Olink AB
Country Sweden 
Sector Private 
PI Contribution The aim of this project is to conduct, in collaboration with Olink, a comparison of the protein expression of plasma samples from patients with active polymyalgia rheumatica (PMR) versus those from control patients of similar age without PMR. We hypothesise our project will lead to the discovery of candidate diagnostic biomarkers for the detection of early-stage PMR. We will then seek to determine the protein identities of the discovered biomarkers to allow for additional validation with independent methods and as a first step toward understanding the pathways in which they may function. We will also use this model to determine and perfect the protocol needed to repeat this work for samples taken from patients with giant cell arteritis. PMR is a disease of older people, it has overlapping clinical features with giant cell arteritis (GCA), and are both treated with glucocorticoids (steroids). There are significant clinical challenges in both the diagnostic and treatment pathways of these related diseases that are treated almost exclusively with glucocorticoids based on a clinical diagnosis. The proposed investigation will address the need for diagnostic biomarker discovery since, at present, there is not one single, affordable and widely available specific test for PMR (or GCA). Without accurate diagnosis, patients with PMR may experience prolonged symptoms and undergo extensive clinical tests due to lack of specificity of existing blood tests to "rule in" PMR. Conversely, patients who do not have PMR/GCA may be exposed to unnecessary steroid treatment due to clinical uncertainty. The samples to be used in this study have been collected for the ADDRESS-PMR study (PI: Dr Sarah Mackie). All patients included in this study were referred with suspected PMR, and provided formal written consent (REC reference number 13/LO/1094) to participate. The samples used for the first part of the proposed project will be those from 45 participants who received a clinical diagnosis of PMR (patients), and 45 participants who were not diagnosed with PMR (controls). 1µL plasma samples will be submitted to the Olink Cardiometabolic and Inflammation panels. From a diagnostic biomarker perspective, these panels have been selected because they include the detection of proteins that the literature suggests may be modulated in PMR. Once the first part of the study has been conducted, we will review the patient and control protein signatures. Depending on these results, we may choose to assay the same samples on a third panel to expand our discovery, or we may select the most useful panel and conduct a comparison of plasma samples taken from 45 patients diagnosed with PMR at baseline, with plasma samples from the same 45 patients after one-month of treatment with prednisolone. We could also explore samples taken from these same patients after 6 and 12 months of treatment. This study would allow us to explore how the potential diagnostic biomarkers are affected when PMR is treated. There is no a priori power calculation on which to base these studies because, as far as we are aware, ours will be the first proteomic investigation of PMR. Olink, however, are highly experienced in conducting novel investigations of this kind and are confident that these sample sizes will yield informative protein signatures. Professor Ann Morgan (PI) will lead this project with support from Charlotte Harden (Programme Manager). Dr Sarah Mackie (Consultant Rheumatologist and Associate Clinical Lecturer) will provide samples with support from Dr Louise Sorenson (Project Manager). Jim Robinson (Research Fellow and Immunogenics Facility Lead) will oversee the technical training of two members of our research team (Research Technicians Lubna Shafi and Steve Martin).
Collaborator Contribution Olink Proteomics provided training to three members of our team (Lubna Shafi, Steve Martin and Dr James Robinson) at St James's Hospital Leeds during 9th - 10th January 2018. These staff have begun the process of certification/Centre Accreditation. They provided two proteomic panels (Inflammation and Cardiometabolic) at a discounted price (25% reduction). These panels were assayed during the training session in January and were repeated (at no additional charge) in Uppsala due to issues with the control samples. Ann Morgan, Charlotte Harden, Sarah Mackie and Jim Robinson will be visiting the Head Office of Olink in April 2018 to have discussions with relevant Olink staff across their service pipeline to develop future studies for polymyalgia rheumatica and giant cell arteritis and to discuss other collaborative opportunities. During this time, Olink will deliver an advanced statistical training session in the analysis of proteomic datasets. This will enable our in-house statistician to comprehensively review data produced by proteomic analysis, and will allow them to build a relationship with experts in the field. We will attend structured meetings to discuss the next phase of the collaboration (in terms of study design, optimising test procedures etc.) and opportunities for iCASE Studentships and knowledge transfer. Specifically, we will discuss the potential to identify novel diagnostic biomarkers of GCA. Finally, we will discuss the possibility of Leeds becoming Olink's sole UK Core Accredited Facility. Olink will provide technical and statistical expertise free of charge for the duration of this project to ensure the most cost-effective and high-quality outcome.
Impact 1) It has provided our research team with new skills in a technology that will add significant value to our programme of research, and value to the future business need for our Immunogenetics Facility. 2) Having in-house skills offers significant advantages compared to outsourcing because it allows greater research flexibility, and will ensure we continually develop deeper intelligence with regard to the complexities, advantages and limitations of proteomic technologies. 3) In-house analysis is cost-saving, as we will not need to outsource this work, and the cost of any further Olink assays will be subject to 25% discount. 4) By achieving Centre Certification, we will be able generate income by offering fee-for-service analysis using Olink's panels to any external party.We will become the only UK provider of this service. 5) Our Medical Statistician will have a unique personal and skill development opportunity through 1-1 training with experts at Olink. It will expedite the accurate analysis of future data and promote best practice. 6) Core, is the opportunity to build a genuine collaboration with Olink. As there are significant projects within our wider programme of research that will benefit from proteomic input, it is critical that we harness the expertise of Olink and take advice in terms of factors such as statistical power, the discovery of biomarker signatures, and developing a customised, validated panel. 7) We will have a unique opportunity to fully explore 'added value' projects. For example, we will discuss the possibility of iCASE Studentships, joining an established ITN network and knowledge transfer. We are keen to understand the wider objectives of Olink and how we may work in tandem on projects with reciprocal benefits. 8) We would also like to take the opportunity to promote our MRC TARGET Partnership, with a view to acquiring Olink as a future member. Olink have already been sent the Partnership Agreement for consideration.
Start Year 2017
 
Description Roche - exploring the benefits of tocilizumab in patients with giant cell arteritis 
Organisation Roche Pharmaceuticals
Country Global 
Sector Private 
PI Contribution We are working in tandem with Roche on a number of collaborative opportunities. For example, they have approached Professor Ann Morgan and Dr Sarah Mackie to speak at high-profile events such as the 'Mission Remission' launch on Wednesday 21st March 2018, and the British Society of Rheumatologists 'Theatre Innovation' session on steroid sparing in rheumatology on Tuesday 1st May 2018. They have also approached Professor Morgan and Dr Mackie (via the publisher MGP) to write a manuscript on the topic of steroid sparing for Guidelines in Practice.
Collaborator Contribution Roche will be providing opportunities for sponsored events that will raise the profile of TARGET. They may also provide funding to support studies that are specifically designed to support the use of Tocilizumab for the treatment of giant cell arteritis.
Impact We have had invitations to represent TARGET at two nationally-important events. We are working with Roche to design further research projects and will provide an update of progress in the next report.
Start Year 2017
 
Description Steroid Sparing in Uveitis group (OSTRICH) 
Organisation University of Birmingham
Country United Kingdom 
Sector Academic/University 
PI Contribution Professor Alastair Denniston is part of a Steroid Sparing in Uveitis group (study is called OSTRICH), led by Sri Sharma in Oxford (Consultant in Medical Ophthalmology)
Collaborator Contribution Scientific Advisor
Impact This collaboration has only just initiated.
Start Year 2019
 
Description Steroid Sparing in Uveitis group (OSTRICH) 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution Professor Alastair Denniston is part of a Steroid Sparing in Uveitis group (study is called OSTRICH), led by Sri Sharma in Oxford (Consultant in Medical Ophthalmology)
Collaborator Contribution Scientific Advisor
Impact This collaboration has only just initiated.
Start Year 2019
 
Description The use of digital multicolour immunostaining using Vectra technology 
Organisation Newcastle Molecular Pathology Node
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution In collaboration with the Newcastle Molecular Pathology Node we are optimising Th1 and Th17 staining in FFPE tissue using the Perkin Elmer Vectra 3.0 Automated Quantitative Pathology System. The Leeds team, comprising Professor Ann Morgan and Dr Hannah Matthieson (a clinical fellow) and have identified potential markers and Professor Ann Morgan and Dr Aruna Chakrabarty (Consultant Pathologist) have been reviewing the staining quality and advising on alternative marker panels. Vectra image analysis by Dr Carey and will be supported by Dr Darren Treanor, (leader of the LIMR Digital Pathology Group) and Dr Derek Magee (Lecturer, School of Computing, University of Leeds) to review whether digital image analysis using model-based machine learning techniques can be applied to this work.
Collaborator Contribution Dr Carey at the Newcastle MRC Molecular Pathology Node is helping us to optimise This allows up to six markers to be applied simultaneously allowing more accurate delineation of CD4+ T-cell populations, which has historically been hampered by the challenges of reliably defining cells with a single antibody.
Impact This collaboration is in its infancy and an update will be provided in the next report. The pilot data produced to date has been used to support a clinical PhD application for Dr Hannah Mathieson for a Wellcome Trust N4ward clinical PhD Fellowship application that was unsuccessful and a successful application to the Leeds Teaching Hospitals Charitable Foundation for 1 years pump-priming funding.
Start Year 2017
 
Description UK GCA data linkage with NCARD-RS 
Organisation National Congenital Anomaly and Rare Disease Registration Service
Country United Kingdom 
Sector Public 
PI Contribution The National Congenital Anomaly and Rare Disease Registration Service (NCARD-RS) records those people with congenital abnormalities and rare diseases across the whole of England. GCA is registered as a rare disease. We are collaborating with NCARD-RS to facilitate linkage to electronic health records data from ~2,300 patients recruited into the UK GCA Consortium, where we have associated pathology, imaging and molecular datasets. Data of this scale and quality could not be obtained through any other route.
Collaborator Contribution NCARD-RS provides registration of individuals with rare diseases and linkage to routinely-collected data (Hospital Episode Statistics, Cancer Registry and prescribing data) from patients across England. UK GCA Consortium patients will be registered to facilitate data linkage. NCARD-RS have already initiated the UK GCA registration process, which will be conducted under section 251 ethical approval.
Impact There are no outputs to report because we are still establishing the information governance processes. We will provide an update in the next submission.
Start Year 2019
 
Description Unravelling the genetic architecture of giant cell arteritis susceptibility and of discrete clinical phenotypes 
Organisation Regeneron Pharmaceuticals, Inc.
Country United States 
Sector Private 
PI Contribution Description: the Regeneron Genetics Center will provide whole exome sequencing of de-identified DNA samples from individuals recruited to the UK GCA Consortium with explicit consent for Industry collaborations.
Collaborator Contribution The primary goal of the study is to unravel the major genetic loci associated with GCA and/or specific GCA phenotypes by performing whole-exome sequencing in well-phenotyped cases recruited to the UK GCA Consortium.
Impact This collaboration is just initiating and we will have outputs to report in the next submission.
Start Year 2019
 
Title BIOlogics in refractory VASsculitis: a pragmatic, randomised, double-blind, placebo-controlled, modified-crossover trial of biologic therapy for refractory vasculitis in adults and children 
Description The vasculitis diseases occur when the body's immune system attacks blood vessels, causing injury to the vessel and the part of the body it supplies with blood. Vasculitis is rare, there are a number of different types, and they affect both adults and children. We treat vasculitis with steroids and drugs aiming to damp down the activity of the immune system, but they often cause side effects. Some patients do not improve with this treatment, or cannot tolerate it and their vasculitis worsens (refractory vasculitis). Such patients are at high risk of health complications from the disease and its therapy and are in need of newer treatments with fewer side effects. Biologics are newer expensive drugs manufactured from biological sources. They are designed to precisely target the immune system and have fewer side effects. Although biologics have been used for some years to treat vasculitis, for many types of vasculitis we do not have good data to guide the correct choice of biologic, and when to use it. Two biologics have been fully tested and are now licensed for the more common forms of vasculitis. We want to establish whether biologics are effective and represent value for money for patients with refractory vasculitis. BIOVAS will look at three different biologics, infliximab (INF), tocilizumab (TCZ) and rituximab (RTX), chosen for scientific reasons and because there is already experience of their use in vasculitis. We will recruit 140 adults and children with refractory vasculitis and compare each drug to a placebo (dummy) treatment. Patients will have the following types of vasculitis: giant cell arteritis, Takayasu's arteritis, polyarteritis nodosa, cerebral vasculitis, Cogan's syndrome, relapsing polychondritis, IgA vasculitis, non-infective cryoglobulinaemic vasculitis. Patients will not be able to take part if they have a serious infection or are pregnant. Treatments will be decided by a process called randomisation (like flipping a coin ). Patients will be assigned to a treatment sequence (e.g. one sequence may be TCZ, then INF, then placebo, then RTX). They will start on the first allocated treatment and stay on it as long as it is helping them; if the treatment does not work, or stops working, they will move to the next treatment in the sequence. Neither the doctor nor the patient will know which treatment they are on unless there is an emergency. All treatments are given through a drip into a vein in the patient's arm. Patients will be seen in clinic at the start of the trial and every four months to see how they are doing. These visits will check whether the treatment is working or not. Patients will be asked to complete questionnaires about how they feel the disease is affecting their lives, as well as recording side effects. The study will estimate the money spent on the patient by the NHS, costs the patient experience due to the disease and whether the disease is affecting their job or education. We hope to show whether biologics work or not, which one works best, what affect they have on patient's health and quality of life, and whether the drug costs can be justified. The BIOVAS study team includes experts in vasculitis and patient representatives. This will help patients in the future to receive the best possible treatment for their conditions. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Refinement. Clinical
Year Development Stage Completed 2019
Development Status Actively seeking support
Impact The study started in 2019 so there are no outputs to report yet. 
URL https://www.fundingawards.nihr.ac.uk/award/17/83/01
 
Description 27th European Academy of Dermatology and Venereology Congress 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A talk on the treatment of ANCA-associated vasculitis
Year(s) Of Engagement Activity 2018
 
Description Annual Northern and Yorkshire Rheumatology Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Presentation 'pharmacoepidemiological studies that help clinicians and patients to weigh the benefits and harms of treatments for GCA'.
Year(s) Of Engagement Activity 2018
 
Description Ask the Researcher - Leeds BRC 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact Ann Morgan and Jim Robinson present to the Leeds BRC PPI group approximately every 2 years. Talks have included the concept of stratified medicine, translation of genetic discoveries into new therapeutic targets and also some practical demonstrations, such as DNA extraction from strawberries, by Lubna Shafi, once of the technical staff in Leeds. These have been very well received and get 30-60 attendees.
Year(s) Of Engagement Activity 2018
 
Description BSR 2020: AN AUDIT OF GLUCOCORTICOID PRESCRIPTION IN PATIENTS WITH GIANT CELL ARTERITIS 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact BSR 2020: AN AUDIT OF GLUCOCORTICOID PRESCRIPTION IN PATIENTS WITH GIANT CELL ARTERITIS. HAIRUL HADI ARIFF, ABID AWISAT, JACK ARNOLD, HUDAIFA AL ANI, LORRAINE O' NEILL, MAR PUJADES RODRIGUEZ, RAASHID LUQMANI, NUFFIELD DEPARTMENT OF ORTHAEDICS, RHEUMATOLOGY AND MUSCULOSKELETAL SCIENCE, UNIVERSITY OF OXFORD, NUFFIELD ORTHOPAEDIC CENTRE, OXFORD, UNITED KINGDOM
Year(s) Of Engagement Activity 2020
 
Description Breakfast Meeting sponsored by Roche Products Ltd/Chugai Pharma UK Ltd 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact The University of Leeds is hosting a Breakfast Meeting to support Roche's launch into GCA research on Wednesday 21st March 2018. Professor Ann Morgan has been invited to Chair this event and to host it at the NIHR Leeds Biomedical Research Centre (Chapel Allerton Hospital, Leeds). The title of this meeting is 'MISSION REMISSION 2018: Time to Act - a novel approach in the clinical management of Giant Cell Arteritis'. This promotional meeting is sponsored by Roche Products Limited and Chugai Pharma UK Ltd. As well as discussing clinical management of GCA, the meeting will contain promotional elements making reference to RoACTEMRA® (tocilizumab). The GiACTA Clinical Study Professor John Stone (Director of Clinical Rheumatology, Massachusetts General Hospital and Professor of Medicine at Harvard Medical School) will discuss the trial outcomes and the future role of RoACTEMRA® (tocilizumab) in GCA. Roche are publicising this event widely to the research and clinical community within their list of contacts.
Year(s) Of Engagement Activity 2018
 
Description British Society for Rheumatology Annual Meeting Spring 2018 Special Interest Group in Vasculitis (convenor). Prof Luqmani chaired the session to discuss updates in vasculitis including a review of TARGET and GCAT registries by Prof Morgan 
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 Working group to review progress in vasculitis research
Year(s) Of Engagement Activity 2018
 
Description Conference presentation - Hospital Optometrists Annual Conference 
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 Dr Sarah Mackie gave an invited talk about giant cell arteritis at the Hospital Optometrists Annual Conference (Queens Hotel, Leeds) on Sunday 8th October 2018. This was a 40 minute talk, followed by a 20 minute question and answer session. Sarah's talk covered the diagnosis, impact and management of GCA. She stressed the important role of Optometrists in the detection of GCA and provided an update of the latest research findings in relation to the detection of GCA through visual examinations. Members of the audience were largely practitioners, and about 25% reported that they had detected suspected GCA through eye examinations and had made hospital referrals on the basis of their findings. Sarah's presentation slides were disseminated to the audience after the event.
Year(s) Of Engagement Activity 2017
URL https://www.aop.org.uk/education-and-events/events/2017/10/07/43rd-hospital-optometrists-annual-conf...
 
Description Delphi consensus 2019 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Delphi consensus to prioritise domains to be used in a glucocorticoid impact patient reported outcome measure for clinical trials. Glucocorticoid Impact Special Interest Group of Outcome Measures in Rheumatology (OMERACT). Web questionnaire, July 29th 2019. International.
Year(s) Of Engagement Activity 2019
 
Description Delphi consensus 2020 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Delphi consensus to prioritise domains to be used in a glucocorticoid impact patient reported outcome measure for clinical trials. Glucocorticoid Impact Special Interest Group of Outcome Measures in Rheumatology (OMERACT). Web questionnaire, Friday 31st 2020. International.
Year(s) Of Engagement Activity 2020
 
Description Demo website 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was a website demonstration to help us build our GCA app. It could be accessed by registered clinicians only.
Year(s) Of Engagement Activity 2018
URL https://riskinstitute.uk/gca/
 
Description EULAR 2020 abstract: No. 283 (AN AUDIT OF GLUCOCORTICOID PRESCRIPTION IN PATIENTS WITH GIANT CELL ARTERITIS) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact EULAR 2020 abstract: No. 283 (AN AUDIT OF GLUCOCORTICOID PRESCRIPTION IN PATIENTS WITH GIANT CELL ARTERITIS)
Hairul Hadi Ariff* 1, Abid Awisat 1, Jack Arnold 1, Hudaifa Al Ani 1, Lorraine O'neill 1, Mar Pujades Rodriguez 2, Raashid Luqmani 1): DOI: 10.1136/annrheumdis-2020-eular.283
Year(s) Of Engagement Activity 2020
 
Description Engagement with PMR&GCA UK 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Dr Sarah Mackie represented TARGET at the PMR&GCA UK AGM on Saturday 9th September 2017 by engaging with their members and other researchers.
Year(s) Of Engagement Activity 2017
URL https://twitter.com/Sarah_L_Mackie
 
Description Funded, half-day PPI event for planning a clinical trial 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact On 21st February 2019, supported by a small grant from the University of Leeds Research Development Fund, I delivered a half-day PPI Event focused around seeking patient and public involvement (PPI) for the planning of a new clinical trial in PMR. We had 8 participants (mixture of local and national, mixture of PMR experience and PPI experience) who provided in-depth feedback to the trials team via several activities including a scripted, dramatised version of a patient consultation, breakout groups, a nominal group-based method for prioritising patient-relevant outcomes, and making a dissemination plan. Feedback from participants led to changes in the design of the planned trial.
Year(s) Of Engagement Activity 2019
URL https://twitter.com/LeedsBRC/status/1098608998897631234
 
Description Invited lecture at the annual meeting of the Society for Primary Care Rheumatology and Musculoskeletal Medicine 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Primary care clinicians from all over the UK attended my plenary lecture at their annual meeting. I discussed updates in research on giant cell arteritis and polymyalgia rheumatica focusing on information that was clinically actionable for GPs. Data provided on formal feedback from the conference organisers indicated that of those giving feedback on the clinical usefulness of the session, 53% of respondents scored it as "excellent", 40% "good" and 7% "average". As a result one GP approached me and this has now resulted in a new research collaboration.
Year(s) Of Engagement Activity 2019
 
Description June 2018 working group 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact This was an organisational meeting for study group members.
Year(s) Of Engagement Activity 2018
 
Description Leeds presentation within QUEST 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact This was a scientific meeting to promote the QUEST research project.
Year(s) Of Engagement Activity 2018
 
Description Media coverage of research article on infections associated with oral glucocorticoid in people with polymyalgia rheumatica 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact The article was covered by over 70 international media outlets, including:
Medical Xpress (Online)
Scien Mag (Online)
BioPortfolio (Online)
India4u.com (Online)
Daijiworldcom (Online)
Daily Hunt (Online)
Prokerala (Online)
Window To News (Online)
SAfrica24 (Online)
IOL (Online)
Can-India (Online)
Andhravilas (Online)
Newsd (Online)
Socialnews.xyz (Online)
Daily World India (Online)
Parallel State (Online)
Healio (Online)
Indian Mirror (Online)
Tech Explorist (Online)
ET HealthWorld (Online)
Canadian Healthcare Network (Online)
The Health Site (Online)
Healthline (Online)
DocGuide.com (Online)
Drugs.com (Online)
Physician's Briefing (Online)
FirstWord Pharma (Online)
HT Syndication (Online)
Web India
Business Standard India (Online)
Devdiscourse (Online)
India New England (Online)
Net India 123 (Online)
Vishva Times (Online)
Doctors Lounge (Online)
Infection Control Today (Online)
Annals of Long Term Care (Online)
Siasat Daily (Online)
Medical Health News (Online)
Community Access National Network (Blog)
Medindia (Online)
Health Europa (Online)
Pourquoi Docteur (Online)
AniNews.in (Online)
Times Now (Online)
University of Leeds (Online)
Frequence Medicale (Online)
7thSpace Interactive (Online)
News-Medical.Net (Online)
Pharma Industry Trade Platform (Online)
Medisite (Online)
News18 (Online)
NewKerala.com (Online)
Pharmscope (Online)
P&T Community (Online)
Physician's Weekly (Online)
Weekly Voice (Online)
Yahoo! US (Online)
RheumatologyAdvisor (Online)
MSN (Online)
The Clinical Advisor (Online)
Dentistry (Online)
Medical Health News (Online)
Physician's Briefing (Online)
Doctors Lounge (Online)
Physician's Briefing (Online)
Physician's Briefing (Online)
Medical Health News (Online)
Drugs.com (Online)
Physician's Briefing (Online)
The Kashmir Monitor (Online)
Year(s) Of Engagement Activity 2019
URL https://cmaj.altmetric.com/details/62606168
 
Description Mission Remission - tocilizumab for the treatment of giant cell arteritis launch 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Professor Morgan provided a keynote talk at the Roche-funded Mission Remission event in the north of England. The aim of this talk was to provide an overview of giant cell arteritis and current care pathways.
Year(s) Of Engagement Activity 2018
 
Description Oxford presentation/poster 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This was a scientific presentation about our work on GCA modelling.
Year(s) Of Engagement Activity 2018
 
Description PMR GCA Public Engagement Roadshow 
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 We collaborated with PMRGCAUK with funding from Wellcome Trust to raise public awareness around GCA and PMR and to share the latest research and developments in causes, treatment and management. After a brief introduction about the Roadshow, participants were asked to choose 2 'Meet the Researchers' session they would like to attend. The session by Lubna Shafi (Research Technician for Professor Ann Morgan) was entitled 'From Genes to Genetic Diseases'. She explained what DNA is, how messages are "coded" within it, and how study of genetic variation in large datasets can give new insights into diseases like GCA. She also included a hands-on strawberry extraction experiment which participants could complete in order for them to have an understanding of how we extract DNA from the blood they give for research purposes and what we use it for. The audience understood more about mutations better after this event, and that, despite having a mutation, you may not be affected by a disease as not all mutations lead to diseases. They also understood that although a mutation predisposes you to a disease, other factors such as lifestyle, diet and environment play a part in disease manifestation. Finally, the audience also had a better insight into how the blood they give for research purposes is used (eg. DNA/RNA extraction, SNP Identification, biomarker discovery). The event was featured in the LMBRU Patient and Public Involvement Newsletter, 'Patients Matter Volume' 9, Spring 2017.
Year(s) Of Engagement Activity 2017
URL http://www.pmrgca.co.uk/content/rheuma-research-roadshows
 
Description PMRGCAUK Patient Group meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact A talk, at Needham market village hall, on the History of PMR and GCA, developments in treatment and future research.
Year(s) Of Engagement Activity 2018
 
Description PMRGCAuk Members' Day talk 
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 On 08/09/2018 I gave an invited talk at the annual PMRGCAuk Members' Day "PMR and GCA Research - what's next?". This was attended by 75 people. In feedback, 12 attendees cited either "the medical speakers", or me by name, as the "best aspect" of the whole day. This led to further engagement from PMRGCAuk in our research planning and two members have agreed to advise on a clinical trial proposal I am developing. The event was reported in the charity's newsletter Newswire which is posted to all members and publicly available online, further increasing the reach of the activity.
Year(s) Of Engagement Activity 2018
URL http://www.pmrgca.co.uk/downloads/1/
 
Description Patient meeting (PMRGCA-UK), Wellcome Trust Rheuma Research Roadshow 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact There is a national patient support group for GCA (PMRGCA-UK). I presented my data at a research roadshow organised by PMRGCA-UK in November 2017 in Newcastle. The roadshow had excellent feedback from attendees (93% very satisfied with "the quality of speakers" and "interest of the content"). The presentation featured in their national e-bulletin and has been made available online (https://vimeo.com/channels/1352513).
Year(s) Of Engagement Activity 2017
 
Description Patient meeting (PMRGCA-UK), Wellcome Trust Rheuma Research Roadshow 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact There is a national patient support group for GCA (PMRGCA-UK). I presented my data at a research roadshow organised by PMRGCA-UK in November 2017 in Newcastle. The roadshow had excellent feedback from attendees (93% very satisfied with "the quality of speakers" and "interest of the content"). The presentation featured in their national e-bulletin and has been made available online.
Year(s) Of Engagement Activity 2018
URL https://vimeo.com/channels/1352513
 
Description Patient website (NewcastleGCA.org) 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact To improve reach further I have built a website to provide information about the GCA clinic in
Newcastle (www.newcastlegca.org). This has a variety of aims:
- It allows participants in this study to learn about how their samples have been used and the
outputs (posters, papers, presentations) that result from their donation
- It will help to improve awareness of GCA amongst the general public and healthcare
professionals, in particular local GPs.
- It provides a single access point for useful external patient resources
- It will help us to communicate about and recruit to further studies
Year(s) Of Engagement Activity 2018
URL http://www.newcastlegca.org
 
Description Patient website (NewcastleGCA.org) 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact To improve reach further I have built a website to provide information about the GCA clinic in Newcastle (www.newcastlegca.org). This has a variety of aims:
- It allows participants in this study to learn about how their samples have been used and the outputs (posters, papers, presentations) that result from their donation
- It will help to improve awareness of GCA amongst the general public and healthcare professionals, in particular local GPs.
- It provides a single access point for useful external patient resources
- It will help us to communicate about and recruit to further studies
Year(s) Of Engagement Activity 2018
URL http://www.newcastlegca.org
 
Description Poster at ENDO 2020: The effect of exogenous Cushing's syndrome on all-cause and cause-specific mortality: A systematic review 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster at ENDO 2020: The effect of exogenous Cushing's syndrome on all-cause and cause-specific mortality: A systematic review. Padiporn Limumpornpetch, MD, Ann W. Morgan, , Ph.D. FRCP,Paul Michael Stewart, MD, FRCP, Mar DM Pujades-Rodriguez, MD, Ph.D.
Year(s) Of Engagement Activity 2020
 
Description Presentation - Leeds Biomedical Research Centre Launch Event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Professor Ann Morgan, Dr Sarah Mackie, Dr Jim Robinson, Dr Ewan Baxter and Dr Charlotte Harden represented TARGET on Monday 11th December 2017 at the Leeds Biomedical Research Centre (BRC) Launch Event. The Leeds BRC is an international leader in translational musculoskeletal research hosted within the Leeds Teaching Hospitals Trust, and bringing together two leading University of Leeds research institutes, the Leeds Institute of Rheumatic and Musculoskeletal Medicine and the Institute of Medical and Biological Engineering, both of which have the delivery of patient focussed research driven by scientific evidence as the core of their activities.The team provided copies of research papers, a poster and digital presentations related to our research themes.This material was targeted at colleagues from across the University of Leeds and Leeds Teaching Hospital Trust as well as current external collaborators and patient representatives. We used this event to raise awareness and understanding about the Biomedical Research Centre and the work we conduct within it. Professor Ann Morgan made a presentation to the BRC board which further raised the importance of the work streams that will be delivered through the TARGET Partnership.
Year(s) Of Engagement Activity 2017
URL http://leedsbrc.nihr.ac.uk/about-us/
 
Description Presentation - Northern NIHR Biomedical Research Centres Showcase 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Dr Sarah Mackie and Dr Louise Sorensen represented TARGET at the Northern NIHR Biomedical Research Centres' Showcase in Manchester in Tuesday 6th March 2018. They presented two posters. Poster 1 provided an overview of the aims of the TARGET Partnership. Poster 2 provided details of projects under our four TARGET work streams. The attendees were predominantly industry, although senior representatives of the Northern Biomedical Research Centres were also in attendance. The team provided hand-outs advertising the collective work of TARGET and had discussion with 15 different industry representatives to explore opportunities for collaboration and skill sharing in the areas of diagnostics, informatics and imaging techniques.
Year(s) Of Engagement Activity 2018
URL http://leedsbrc.nihr.ac.uk/event/northern-nihr-biomedical-research-centres-showcase/
 
Description Presentation to Medical Ophthalmology Society, March 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact I was invited to give a clinical update on giant cell arteritis to an audience of medical ophthalmologists. I based this on an understanding of diagnostic test evaluation that I had acquired during my Clinical Lectureship and Clinician Scientist academic training, and focused particularly on areas that I had personally worked on. The talk included a "show of hands" to test attendees' prior knowledge in this topic area. At the end of the talk all audience participants raised their hand to indicated that they had learned something new that they could apply to their clinical practice.
Year(s) Of Engagement Activity 2019
 
Description Research update for Vasculitis UK Bulletin, Autum 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 Communication to patients of progress with ongoing research studies
Year(s) Of Engagement Activity 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 TARGET AGILE TRAINING 
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 We held an AGILE training event for 15 TARGET members on Tuesday 28th January. Lisa Walker (Certified Scrum Master) delivered this session with her colleagues John Carey and Muriel De Vos (all from Roche Products Ltd.) The aim of the event was to give TARGET members an overview of AGILE and to train us in the basic techniques and concepts. There were 15 attendees, a mix of clinicians, researchers, scientists, study co-ordinators and patients.
Year(s) Of Engagement Activity 2020
 
Description TARGET Scientific Meeting 
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 We held a TARGET Scientific Meeting in Cambridge on Thursday 26th - Friday 27th September. Before the meeting started our Scientific Advisory Board held their inaugural meeting. The main event then opened with an introduction from Professor Ann Morgan, and a review of TARGET progress. We then had invited talks from:
1) Kornelis (Niels) van der Geest, Clinical Research Fellow, Southend University Hospital, Post-Doctoral Researcher, University Medical Center Groningen
- Ultrasound and Halo Scoring as a tool to evaluate GCA
2) Susan Mollan, Consultant Ophthalmologist, University Hospitals Birmingham NHS Trust
- Temporal artery imaging in suspected Giant Cell Arteritis using the SPECTRALIS Optical Coherence Tomography FLEX ModuleTM
3) Peter Lanyon, Consultant Rheumatologist, Nottingham University Hospitals NHS Trust
- The Getting It Right First Time (GIRFT) rheumatology programme: exploring variation in GCA service delivery across the NHS in England
4) Rahaymin Chowdhury, ST4 Registrar, Harrogate and District Foundation Trust
- Diagnosing Giant Cell Arteritis (GCA): Can probability scoring improve our Leeds Teaching Hospital Trust (LTHT) diagnostic pathway?
5) Aruna Chakrabarty, Consultant Histopathologist, The Leeds Teaching Hospitals NHS Trust
- Histology scoring atlas for GCA
6) Jo Robson, Consultant Senior Lecturer in Rheumatology, Faculty of Health and Applied Science, UWE Bristol
- Development and validation of a patient reported outcome measure for Giant Cell Arteritis: GCA PRO
7) Allan Wailoo, Professor of Health Economics, Director NICE Decision Support Unit, University of Sheffield
- NICE requirements for evidence: an example from biologic appraisals
8) Jianhua Wu, Associate Professor in Medical Statistics and Biostatistics, University of Leeds
- Glucocorticoid dose and the risk of type 2 diabetes in patients with 6 autoimmune diseases
9) Hairul Hadi Ariff, Research Fellow, University of Oxford
- An audit of steroid prescription in patients with GCA
10) James Peters, UKRI Innovation Fellow at Health Data Research UK, University of Cambridge, and Honorary Consultant Rheumatologist at Addenbrooke's and Barts Health NHS Trust
- The promise of multi-omics in understanding vasculitis aetiology
11) Euan Baxter, Research Fellow, University of Leeds
- Identification of novel macrophage phenotypic markers
12) Lihui Wang, Post-doctoral researcher, Kennedy Institute of Rheumatology, University of Oxford
- Human immature neutrophils as a functional biomarker of systemic vascular pathologies
13) Gary Reynolds, Clinical Lecturer at Newcastle University and Specialty Trainee in Rheumatology at the Freeman Hospital
- The role of DNA damage in the formation of Langhans-type multinucleated giant cells

On Friday we offered two parallel sessions:
1) Need for epidemiological data in GCA, Chair: Dr Mar Pujades Rodriguez OR Health Economics, Chair: Professor Chris Bojke
2) BSR GCA Guidelines, Chair: Dr Sarah Mackie OR Genetics and Genomics Studies, Chair: Professor Ann Morgan
The final session was a roundtable discussion on next steps for TARGET.
The event was attended by 102 colleagues from academia, industry and the NHS. The patient representatives on our Partnership Board attended. Sponsorship for the event was provided by Roche Products Ltd. (£5k) and Kiniksa Pharmaceuticals (UK) Ltd (£5k).
Year(s) Of Engagement Activity 2019
 
Description TARGET Scientific Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact We held a TARGET Scientific Meeting in Leeds on Friday 5th October 2018. The meeting opened with an introduction from Professor Sir Alex Markham Professor of Medicine, University of Leeds. We then had invited talks from: Professor Ann Morgan, Professor of Molecular Rheumatology and Honorary Consultant Rheumatologist, University of Leeds
- Overview of the TARGET Consortium; Dr Mar Pujades Rodriguez, University Academic Fellow, University of Leeds - What can electronic patient record data tell us about steroid toxicity?; Professor Raashid Luqmani, Professor of Rheumatology and Consultant Rheumatologist, University of Oxford - The GCAT Registry (post-marketing surveillance registry for the use of tocilizumab in the treatment of Giant Cell Arteritis); Dr Sarah Mackie, Associate Professor and Honorary Consultant Rheumatologist, University of Leeds - Mind the (evidence) gap: could trials-within-cohorts help fill evidence gaps in GCA?; Dr Pani Gopaluni, Clinical Research Fellow, University of Cambridge - The BIOVAS study (biologic agents in non-ANCA vasculitis); Dr Kerryn Symons, Country Medical Leader, Roche Products Ltd - Research gaps in GCA: an industry perspective. We then had seven parallel sessions, and further group sessions to determine our future research streams. The event was attended by 98 colleagues from academia and the NHS. The patient representatives on our Partnership Board also attended. Sponsorship for the event (£10kGBP) was provided by Roche Products Ltd.
Year(s) Of Engagement Activity 2018
URL https://lida.leeds.ac.uk/target/targetscientificmeeting2018/
 
Description Talk on PMR and GCA research to Ilkley Support Group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact I delivered a talk about research in PMR and GCA and the value of clinical trials. This was the start of a series of interactions with this local group which has subsequently been very useful in understanding the patient perspective about both about our clinical service and several of our research studies.
Year(s) Of Engagement Activity 2018
 
Description Treatment According to Response in Giant cEll arTeritis 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact An invited presentation to PMRGCA UK. The TARGET Programme Manger gave an overview of the TRAGTE aims and objectives and highlighted the research conducted so far in our programme of research.
Year(s) Of Engagement Activity 2018
 
Description Visit to a meeting of the PMRGCAuk Ilkley Support group 
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 On 12th March 2019 I again visited a meeting of the PMRGCAuk Ilkley Support Group. They had planned a Q+A round-table session with Dr Pease, another Leeds rheumatologist, which lasted around an hour. 19 patients and 1 carer were present. After the Q+A I spent half an hour talking with attendees about how they kept track of their steroid dose, what their needs were regarding support for this, and obtained useful feedback about their attitudes to future clinical research in this area, which they felt was greatly needed. This has informed the direction of a current grant proposal. Two participants expressed willingness to be involved in development of this.
Year(s) Of Engagement Activity 2019