MICA: Immune-Mediated Inflammatory Disease Biobanks in the UK (IMIDBio-UK)

Lead Research Organisation: University of Glasgow
Department Name: College of Medical, Veterinary &Life Sci

Abstract

Immune-mediated inflammatory diseases (IMIDs) are common medical conditions that cause substantial pain, distress, loss of function and early death. They are clinically diverse e.g. by variously targeting the skin, joints, or kidneys, but share some common genetic features, environmental triggers and inflammatory pathologic mechanisms. The IMIDs include rheumatoid arthritis (RA), psoriasis, systemic lupus erythematosus (SLE), Sjogren's syndrome, autoimmune hepatitis and primary biliary cirrhosis. Since the 1990s, biologic drugs and improved treatment strategies have revolutionised the treatment of a significant proportion of people with some IMIDs. However some IMIDs have not really progressed and even in those in which advances are notable, many patients do not yet respond to treatment or lose their responses over time - this in life long incurable diseases. Therefore, there remains great unmet clinical need in the IMID field.

One exciting approach to improving outcomes is to apply the principles of precision medicine whereby patients will receive the 'right drug at the right time at the right dose' with minimal chance of having significant toxicity. Bringing precision medicine to IMIDs will require large datasets that integrate clinical information together with complex molecular datasets that can now be generated from the blood and damaged tissues that occur in IMIDs. In theory, by putting this information together we can create a 'molecular map' of a patient that allows very precise treatment decisions to be made that will bring better outcomes at reduced risk. Thus far however most IMID collections of such data have been specified for only one disease leading to a rather narrow approach to the broader inflammation medicine field. This proposal will revolutionise this scenario by bringing together many UK biobank and clinical cohort datasets into one single searchable and analysable entity, lead and coordinated by a consortium called IMIDBio-UK. IMIDBio-UK will generate a virtual information superhighway that will allow unprecedented access to information about IMIDs across the UK.

The vision of the IMID-Bio-UK consortium is to harness the power of a rich reserve of biosamples, deeply phenotyped clinical cohorts, and high quality multi-omic data formed from a group of highly successful national stratified medicine programmes. These resources will be made available to researchers to study IMID biology and predict drug response, using molecular markers (biomarkers) to define common and unique mechanisms (endotypes) of disease progression and drug action. This will enable wider, safer use of biologics and new medicines across the IMID spectrum. By bringing together IMID samples and comparing data and clinical practice, we will optimise clinical pathways for common IMIDs, and provide much needed insight into biologic use in rarer or poorly characterised IMIDs, ultimately delivering patient benefit and health care savings.

Technical Summary

Immune-mediated inflammatory diseases (IMIDs) are phenotypically diverse, but share genetic & environmental susceptibility factors & common inflammatory mechanisms. Therapeutics of IMIDs have been revolutionised by specific biologic immune modifiers and immune receptor kinase inhibitors. Discrete responses emerging to given agents across IMIDs suggest the existence of both common and disease restricted pathways. Current immune therapies are prescribed without precision medicine principles. Incomplete response is not uncommon, depending on disease and drug and risk of serious toxicities remain problematic. Collectively these issues, combined with high costs have limited biologic use in the NHS, particularly in rarer IMIDs where disease aetiology and mechanism are not well understood. This is a key area of unmet need. We propose a systems approach to address these challenges that will rely heavily on the presence of large well characterized clinical biobanks informing across IMIDs. This will require significant new bridging infrastructures, including more robust biorepositories that link human tissue to phenotype and outcome. IMID-BIO-UK will address these challenges directly. We will unite several disease biobanks together to create a unique IMID tissue and data repository, unparalleled in scale and scope, to (1) examine disease specific and common endotype concepts across IMIDs beyond those facilitated by existing disease specific cohorts using advanced classification on multi-omic data, and by leveraging clinical cohort databases; (2) focus particularly on blood / tissue biopsy comparisons across IMIDs; (3) integrate multiomic data across tissue compartments including blood and understand the disease specific and common endotype inter-relationship across IMIDs; and (4) use such knowledge to enable rapid repositioning and stratification of therapeutics across IMIDs and enable access for POC studies.

Planned Impact

Patients with immune-mediated inflammatory disease (IMID) will directly benefit from the improvement in drug development and the stratification of therapeutic options that will be facilitated by IMIDBio-UK. The impact of developing new stratification algorithms that will identify patients most likely to safely respond to a specific therapy will revolutionise IMID healthcare. IMID-Bio-UK will benefit patients with highly prevalent IMIDs such as rheumatoid arthritis (RA), psoriasis, immune mediated liver disease and connective tissues diseases such as systemic lupus erythematosus (SLE) and Sjogrens syndrome who could be treated on the basis of common IMID mechanisms rather than specific disease pathways. IMID-BioUk will harness the power of a rich reserve of biosamples, deep phenotyped clinical cohorts, and high quality multi-omic data formed by integrating the activities and resources of several highly successful stratified medicine initiatives and thus form a legacy for national stratified medicine programmes that will be world class and globally competitive.

Understanding the shared immunological perturbations that drive IMID development will provide a platform for novel therapeutic pathway discovery that has real potential for developing curative interventions. Such knowledge will also open up an unprecedented possibility for designing disease prevention strategies for IMIDs. Successful development of such novel interventions will represent a major improvement in the management of IMIDs, which impact on patients as well as the clinicians providing their care, the pharmaceutical industry and healthcare policy makers.

Both the National Institute for Health and Care Excellence (NICE) and the Medicines and Healthcare Regulatory Agency (MHRA) in the UK will benefit from stratification in that patient pathways and guidance for starting and/or switching biologics will gain a substantial evidence base, beyond that of the existing stratified medicine initiatives. More efficacious and/or cost-effective treatment would have significant impacts on the resource limited NHS.

IMID-Bio-UK not only strengthens the existing network between clinicians, scientists and industrial partners with interests in IMIDs, but also establishes new links across the IMID stratified medicine community. The broadened skill base will facilitate synergistic cross-disciplinary interactions in the field of IMID research. Furthermore, the Informatician-clinician working partnership fostered by IMID-Bio-UK will help to train the "next generation" clinician scientists to move from systems biology to systems medicine, bridging an imperative knowledge gap, identified by UK funders. Finally under the leadership of Arthritis Research UK we will bring together a consortium of charities with common purpose in the IMID area to optimise policy and advocacy across disciplines with relevant stakeholders.

Publications

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Title Commencing Harmonisation of Databases in IMID 
Description This is the primary purpose of this grant that has only recently started - no other outputs to report as yet. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? No  
Impact None as yet