Close

We're using cookies to give you the best experience on our site. Cookies are files stored in your browser and are used by most websites to help personalise your web experience.

By continuing to use our website without changing the settings, you're agreeing to our use of cookies.

Find out more
For more information, go to www.arthritisresearchuk.org

Focus on Manchester University

Published on 01 October 2009
Source: Arthritis Today

Arthritis Research UK Epidemiology Unit Manchester

The dedicated multidisciplinary team of scientists at the Arthritis Research UK Epidemiology Unit is unravelling the complexities of disease susceptibility.

Identifying the factors that influence arthritis development and treatment response is a tough challenge. But thanks to its excellent research base and a healthy research income, including core funding of £2.4m per annum over 4 years from Arthritis Research UK, the dedicated multidisciplinary team of scientists at the Arthritis Research UK Epidemiology Unit is unravelling the complexities of disease susceptibility and treatment outcomes and translating its findings into improved patient care.

Why are some people more likely to develop arthritis than others, what common factors influence disease development, and what determines how safe or effective treatments are for different individuals? The answer lies in epidemiology, the study of factors affecting the health and illness of populations.

At the Arthritis Research UK Epidemiology Unit (EU) in the University of Manchester major studies to track the causes, outcomes and treatment of musculoskeletal disorders are yielding important findings that will advise clinical practice and inform new therapy developments.

This prestigious unit, part of the Research School of Translational Medicine within the Faculty of Medical and Human Sciences, is the largest independent epidemiology centre in the world. Established by the charity in 1954, it conducted the first UK population surveys of rheumatic disease and then evolved to investigate the predictors and outcomes of disease, and more recently the effectiveness and safety of treatments.

The EU is structured into four major divisions: inflammatory disease, non-inflammatory disease, genetics, and statistics and computing, the latter being hugely important to plan and handle the vast quantities of data that is generated by the studies. It is a multidisciplinary effort involving clinicians, geneticists, epidemiologists, healthcare workers, mathematicians and statisticians, and many more.

Genetics and environment: the risk factor studies

Professor Deborah Symmons, Medical Director and Head of Unit, describes the focus and complexity of its operations: “Modern epidemiology looks at all the risk factors that influence disease development and its treatment. We use blood analysis, patient questionnaires, and clinical assessments to monitor patients over several yeas. Our aim is to assess which factors are important and use this knowledge to identify and reduce the risk to individuals and to devise appropriate treatment protocols to minimise disease progression.

“We know that there is a strong genetic component to arthritis – the hereditary risk factor. We need to know which of the millions of genetic markers in the human genome are responsible for this. And it isn't just one marker for one disease – multiple combinations of markers predispose an individual to developing disease. In addition, there are non-genetic, or environmental, factors such as lifestyle, diet, exercise and infection. All of these factors can interact and influence susceptibility to disease development and severity, and we need to follow thousands of study participants long-term to identify them.”

Several major long-term studies are yielding results that will impact on patient care. The Childhood Arthritis Prospective Study (CAPS) has been recruiting and monitoring children with recent onset inflammatory arthritis at five centres around the UK since 2003 and is identifying risk factors for disease development and predictors of outcomes.

The Norfolk Arthritis Register (NOAR) study is approaching its 20th year and has recruited over 4,000 patients with recent onset inflammatory polyarthritis since 1990. The study has established the benefits of early and effective drug therapy and is yielding vital information on complications such as heart disease. The Non-Inflammatory division of the EU is involved in a large European Male Ageing Study (EMAS) that is providing information on the incidence of musculoskeletal pain and how genetic factors may influence susceptibility to pain.

The analytical challenge

Professor Jane Worthington, Scientific Director of the EU, describes how technological advances in genetic research have dramatically increased the size and complexity of the studies: “When the entire human genome (the total genetic material of our DNA) was mapped out, genetic studies were revolutionised. Now we can analyse all the genetic markers that exist, and for each individual this may be a million markers. Despite having sophisticated, rapid throughput analysers to do this, the workload and the volume of results is still huge. Consider taking one small blood sample from an individual and analysing all the markers, then multiply this by all the thousands of individuals in the survey. This provides us with such an amazing analytical capability but it's still a formidable challenge.”

Studies have to be statistically robust; data has to be captured, stored and manipulated, and results analysed and evaluated. The capacity of the computer storage system has recently exceeded one terabyte, that's 1012 (1,000,000,000,000) bytes of digital information!

Predicting susceptibility and outcomes

Jane Worthington and Deborah Symmons

So how will this information be used to benefit arthritis research? Professor Worthington explains: “By understanding the genetic basis of these disorders, we can start to devise novel therapies to combat them. We're not there yet but other disease areas are already starting to achieve this and we're confident that the same thing will happen in arthritis research. Interestingly, the same markers are being identified in other inflammatory conditions, suggesting that they programme a common underlying mechanism. Establishing genetic risk factors for disease susceptibility will allow us to predict who is most likely to develop conditions and how severely. We'll be able to treat people early to prevent tissue damage. Some of these genetic markers are linked to how well the body will respond to certain drug therapies. If we can predict who will respond well, and who won't, we can tailor treatments to the individual, avoid wasting time, resources, and unnecessary adverse effects, and improve patient outcomes by administering the most appropriate and effective therapies.”

Equally significant findings are emerging from non-genetic research. The British Society for Rheumatology Biologics Register tracks the progress of patients with severe rheumatoid arthritis and other rheumatic conditions who are taking anti-TNF drugs. This is the largest international register of its kind in the world.

“We have established that patients who respond to anti-TNF therapies have a marked reduction in the incidence of heart attacks during their first 6 months of treatment,” says Professor Symmons. “This has important clinical significance in terms of the links between inflammatory arthritis and the inflammatory aspects of cardiovascular disease. It's likely that the same inflammatory mechanisms are contributing to these conditions and that both genetic and non-genetic factors are influencing their development. For example, we have found that smoking increases the susceptibility risk for arthritis and shown that a combination of smoking and specific genetic and immune factors increases the risk of cardiovascular disease in patients with inflammatory arthritis.”

It's not just the obvious lifestyle factors that influence disease progress. “Some patients don't have a positive attitude to their treatment,' says Professor Symmons, 'and psychology is a powerful factor influencing outcomes. If patients don't believe that the drugs will work, they may not benefit as much. Many patients don't take their tablets routinely and this non-compliance can be a major bias in the studies. We use psychologists and specially trained healthcare workers to design and administer questionnaires to take this into account.”

Co-operation and clinical involvement

Alongside the expertise of the multidisciplinary workforce, the cooperation of patients and clinicians is key to the success of this unit. “We are very fortunate in the UK,” comments Professor Symmons. “We have an excellent network for carrying out these studies, with enthusiastic clinicians and healthcare staff, and willing patients. The National Institute for Health and Clinical Excellence (NICE) and the British Society for Rheumatology's advice that all patients should go on the Biologics Register has boosted our study population for this survey significantly and the introduction of NHS-funded research nurses has transformed the coordination of clinic involvement. As a result, we can generate more samples in some studies than the whole of the US or Europe.”

Helpline

0800 5200 520

Our new helpline: Call us for free information, help and advice on your type of arthritis. Open Mon–Fri 9am–8pm.

All calls are recorded for training and quality purposes

Virtual Assistant

Our new Arthritis Virtual Assistant uses artificial intelligence to answer your arthritis related questions 24/7.

Ask a question
Close

We're now

Versus Arthritis.

You're being taken through to our new website in order to finish your donation.


Thank you for your generosity.

For more information, go to www.arthritisresearchuk.org/arthritis-information or call 0300 790 0400 to order the complete printed booklet.
Arthritis Research UK fund research into the cause, treatment and cure of arthritis. You can support Arthritis Research UK by volunteering, donating or visiting our shops.