The Musculoskeletal Disease theme aims to reduce health inequalities for patients with immune-mediated inflammatory diseases and musculoskeletal conditions through accurate detection, early diagnosis, and identification of personalised therapeutic targets.
Overview
Musculoskeletal diseases (MSKDs) are the leading cause of chronic disability and among the most expensive to treat, costing NHS England over £10 billion annually. MSKDs affect 1 in 4 people in the UK, with the global prevalence increasing by 25% in the past decade.
Immune-mediated inflammatory diseases (IMIDs) are a large group of inflammatory and autoimmune non-genetic rare diseases. They affect multiple organ systems that require long-term treatments targeting the immune system. Musculoskeletal conditions, especially osteoarthritis, are common, often age-related, and associated with lifestyle factors.
Focusing on accurate detection, early diagnosis, and discovery of new treatment approaches through interdisciplinary collaboration, we aim to:
- Identify individuals at risk of IMIDs to prevent the onset of inflammation and complications
- Reduce the harmful effects of glucocorticoids, development of multiple long-term conditions (multimorbidity), and frailty
- Develop personalised, cost-effective therapies for common and impactful MSK conditions
Since 2008, NIHR Leeds Biomedical Research Centre has combined excellence in translational MSKD research with bioengineering and is host to the largest international academic facility for pre-clinical testing of joint replacements.
Theme Lead: Prof Ann Morgan
WS1: Rheumatoid arthritis (RA) prevention and stratified interventions
WS2: Prevention of psoriatic arthritis
WS3: Intervention in connective tissue disease and autoinflammatory diseases
Leads: Prof Paul Emery & Dr Kulveer Mankia
Our goal is to improve the prediction and prevention of rheumatoid arthritis (RA). Preventing RA and other incurable autoimmune diseases has become a major research priority, with the potential to transform clinical rheumatology practice.
RA is one of the most common autoimmune diseases. People with RA experience musculoskeletal pain and disability, and the condition is linked to multiple other health issues, increased mortality, and high NHS costs. Although treatments can be effective, there is no cure for RA, and some patients do not find a treatment that works for them.
Our main focus is to enhance our ability to identify people at risk of RA, accurately assess their risk, and provide tailored early interventions. Using unique data from our large research cohorts, we will develop accurate and practical risk assessment tools. These tools will help us conduct interventional trials for those at risk of RA and those in the very early stages of the disease.
Psoriatic arthritis (PsA) can occur in 30% of people with psoriasis (PsO). Both conditions are chronic and can significantly impact people’s lives, leading to substantial economic costs.
The goal of the WS2 group is to understand which PsO populations are at risk of developing PsA and to find innovative remission strategies.
To achieve this, we are working to understand the link with immunobiology by studying the mechanisms of normal enthesis to comprehend the progression from PsO to PsA.
We are developing diagnostic and treatment algorithms, including polygenic risk scores. Additionally, we have partnered with academics and industry leaders to validate imaging and progression biomarkers and explore new pharmacological strategies to modify risk factors and prevent PsA.
Connective Tissue Diseases (CTDs) are a complex and diverse group of immune-mediated inflammatory diseases, often resulting in severe morbidity or mortality for patients.
Building on our existing, internationally recognised, patient-centred research cohorts, our work aims to identify patients who are at risk of developing CTD and modify the disease course.
Focussing on systemic lupus erythematosus, systemic sclerosis, Sjögren’s syndrome and myositis, we will utilise robust clinical, imaging and biomarker data to inform future clinical management strategies.
Our long-term goal is to improve outcomes for patients, through optimisation of diagnostic pathways, clinical trials of novel therapeutics and ultimately identifying strategies for prevention of disease onset.
WS4: Early accurate diagnosis and precision prescribing in vasculitis
WS5: Safer glucocorticoid therapy in polymyalgia rheumatica (PMR) reducing frailty
WS6: Osteoarthritis stratification for targeted intervention
Leads: Prof Ann Morgan & Dr Mark Iles
Giant cell arteritis (GCA) is the most common type of vasculitis that exclusively affects older adults. This disease can be difficult to diagnose and may cause severe health issues such as blindness and structural changes within blood vessels, such as the aorta. Glucocorticoids or “steroids’ are central to treatment with many patients experiencing complications from glucocorticoid treatment.
Our ultimate vision is to achieve glucocorticoid-free treatment approaches and reduce long-term disease burden and treatment complications.
By leveraging national research groups and studies led by Leeds, we aim to revolutionise the diagnostic and treatment landscape with innovative strategies grounded in molecular diagnostics, including polygenic risk scores (PRS). In partnership with industry, we will develop a cutting-edge platform to validate new treatment targets and facilitate the NHS’s adoption of these advancements through new health economic assessment tools.
Leads: Prof Andrew Clegg & Dr Sarah Mackie
Polymyalgia rheumatica (PMR) is a common inflammatory musculoskeletal disease that causes pain and stiffness around the shoulders, hips and neck. The mainstay of treatment is long-term glucocorticoids (also known as corticosteroids or “steroids”). Glucocorticoid treatment can cause many complications; the higher the dose used, and the longer the treatment continues, the more likely those complications are to occur.
Recent years have seen rapid advances in our knowledge about PMR. This new knowledge has led to proposals for new ways of treating PMR, so that the disease can be brought under better control without causing so many treatment-related side-effects. Clinical trials are needed to test these new ways of treating PMR.
Using primary care databases, we will develop models that can identify at an earlier stage which patients with PMR are at higher risk of developing long-term complications.
In parallel, we will develop infrastructure to facilitate early-phase clinical trials in PMR, so that it will be easier in future to develop new treatments.
Leads: Prof Philip Conaghan & Dr Sarah Kingsbury
We investigate the causes of osteoarthritis (OA) pain in 2 ways.
Firstly, we use novel machine learning methods to accurately measure 3-D joint structures on MRI, and how these relate to weight-bearing symptoms.
Secondly, systemic low levels of inflammation, commonly seen in conditions such as diabetes and obesity, are important in the pain experienced by some people with OA. We are exploring how systemic inflammation relates to OA symptoms, to define a subgroup which may respond to therapies targeting this inflammation.
We will investigate new OA therapies and helps design early phase trials for symptoms, and for structural targets.
WS7: Optimised joint replacement technologies
Leads: Prof Ruth Wilcox & Prof Anthony Redmond
We aim to deliver optimum treatment for every patient requiring joint replacement in the most cost-effective way.
Pre-COVID, 250,000 joint replacements were performed each year in the UK, increasing to 400,000 by 2035, with a 15% rise in revision surgery over the last 5 years. Young, active and obese patients place greater demands on implants.
We will build on our unique capabilities in experimental simulation and computational modelling, incorporating individual patient data from biomechanical measurements and imaging, enriched for at-risk cohorts.
We will generate new pre-clinical evidence, validated through clinical data (retrievals, patient outcomes), to identify key factors that will improve implant performance.