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For more information, go to www.arthritisresearchuk.org

New centres to carry on the work of the world renowned epidemiology unit

Published on 14 April 2014
Source: Arthritis Today

Our epidemiology unit in Manchester has enjoyed an enviable reputation as a leader in its field and has now reinvented itself as two new separate but linked centres. Jane Tadman reports.

During its 60 years of existence the Arthritis Research UK Epidemiology Unit at the University of Manchester has made a massive contribution to finding out the causes of inflammatory arthritis and the factors that increase the risk of developing it.

Epidemiology can be a difficult concept to grasp, but essentially it means the study of factors that either increase or decrease the risk of someone developing a particular disease, how severely they will get it and how they will respond to treatment.

Courtesy of research from the unit, it’s now widely accepted that smoking, eating lots of red meat and insufficient quantities of fresh fruit and vegetables are all risk factors for inflammatory arthritis. More recently, the unit helped to establish that anti-TNF therapy can reduce heart attacks by lowering inflammation in the body, and tracked down large numbers of genes that predispose people to developing rheumatoid arthritis – all significant findings that have had a big impact on people’s lives.

This year the epidemiology unit becomes two new centres – the Arthritis Research UK Centre for Genetics and Genomics and the Arthritis Research UK Centre for Epidemiology – with £2.4m awarded to each centre from Arthritis Research UK over the next five years.

Moving into stratified medicine

Professor Jane Worthington and Professor Deborah SymmonsWhile both centre directors, Professor Jane Worthington (genetics and genomics) and Professor Deborah Symmons (epidemiology), talk about continuity and building on what’s gone before, they are also keen to stress the new and the novel, and the sense that their research is moving on and now has a fantastic opportunity to make an even bigger practical difference to the lives of arthritis patients.

Now that investigators from the centre for genetics and genomics have discovered so much about the genetic risk factors for inflammatory arthritis – in particular rheumatoid arthritis – they can start to dig deeper into understanding what having a particular set of genetic variants actually means for patients. This is basically what the term ‘genomics’ means. The aim is to combine this knowledge with information on non-genetic risk factors in order to develop methods to predict who will get inflammatory arthritis, when and how severely, and to target specific drugs at particular groups of patients who are likely to respond to them without developing side-effects – in other words to ‘stratify’ treatment, to use the current buzzword. 

“We are starting to move beyond the population risk to more specific risks for groups and individuals based on their gender, age and risk factor profile,” explains epidemiology centre director Professor Deborah Symmons.

“There is a growing realisation that it’s wrong to think that everyone gets the same disease by following the same route – there are many routes into it. In addition treatment costs so much, and it’s money wasted if you give someone a drug that is not going to work for them, so there is a lot of interest in investing in this type of work.”

Professor Worthington concurs: “It’s a bit of a blunt instrument to group all patients together and call it rheumatoid arthritis. Hopefully the work we do will help to identify sub-categories, making it easier to choose the right treatment first time.

“To date we have found, in collaboration with others around the world, just over 100 genetic markers for rheumatoid arthritis; the next thing is to get a better understanding of what carrying these variants really means. It will lead us more into understanding of disease mechanisms and may help us to find out what combination of risk factors it takes to make a person susceptible. 

“We have a lot of drug therapies targeted at improving symptoms, but we would like to find therapies that are curative. We think understanding what causes things to go wrong in the first place will pave a better route to finding them, or it might be that existing drugs will work better if we can get them to patients earlier.”

The centre for genetics and genomics is specifically looking at which genes increase the risk for developing rheumatoid, psoriatic and juvenile idiopathic arthritis (JIA), and while Professor Worthington describes the rheumatoid arthritis work as ‘trailblazing’, she concedes that research is less advanced in the latter two diseases.

Professor of rheumatology Anne Barton is heavily involved in investigating the genes that predispose people to psoriatic arthritis. She believes the condition is a neglected area in terms of research, and that if these genes can be identified it could lead to drugs specifically being developed for psoriatic arthritis. (Currently all drugs used in psoriatic arthritis were originally developed to treat rheumatoid arthritis.) A number of research papers are in the pipeline.

Professor Barton is also investigating factors that predict who will respond best to different treatments, including methotrexate and anti-TNF therapy, and is also exploring why people sometimes don’t take their medication as prescribed and what effect this has on treatment response. With colleagues, she also recently published research which revealed that depression is far more common in people with severe rheumatoid arthritis than previously reported.

Drug registers and biobanks

None of the centres’ work would be possible without the involvement of large numbers of patients willing to donate samples and medical information to several large research databases, registers and biobanks. For example, over the past 12 years the epidemiology unit has run the BSR Biologics Register for Rheumatoid Arthritis (BSRBR-RA), which is the largest register of its kind in the world, involving over 15,000 patients with rheumatoid arthritis on a range of biological therapies. The BSRBR-RA has enabled research teams to measure and assess the safety and potential toxicity of biological drugs such as anti-TNF therapy over a period of years.

Professor Anne Barton and Dr Kimme HyrichDr Kimme Hyrich, reader in musculoskeletal epidemiology, is in charge of two registers for JIA, one for children on etanercept – the only biological therapy currently licensed for children with JIA – and the second, supported by Arthritis Research UK, of up to 250 youngsters who are taking one of seven other biological therapies off-licence. These databases are enabling researchers to look at potential long-term benefits and risk of these therapies.

Another important JIA study is the Childhood Arthritis Prospective Study, or CAPS, run by professor of genetic epidemiology Wendy Thompson, which must be one of the few important biobanks in the UK to have its own mascot, Capsie the monkey, who even has his own blog! CAPS was set up in 2001 and is a multi-centre study involving the collection of data and samples from youngsters diagnosed with JIA. There are now 1,300 children on this register, providing a valuable resource for researchers in the centres and further afield. Arthritis Research UK has recently renewed its funding of CAPS for another 18 months.

A number of studies have been published using CAPS data, helping researchers and doctors to understand some of the genetic factors associated with the development of JIA and in predicting outcomes.

In May the centres of epidemiology and genetics and genomics will hold a combined celebration to mark their launch, 60 years of epidemiological research at the University of Manchester and the long association with Arthritis Research UK.

It will also mark the retirement as director of the epidemiology unit for Professor Symmons, who will continue in the role of professor of rheumatology and musculoskeletal epidemiology within the University of Manchester

Says Professor Symmons: “The epidemiology unit is part of the legacy of both new centres and we feel our future work will be a continuation of what we have been doing and build on what we did before. During the 60 years the centres have had many different names – at least one per director! This is just another transformation.”

The new centres in a nutshell

The Arthritis Research UK Centre for Genetics and Genomics aims to improve the quality of life for patients with inflammatory arthritis by increasing the understanding of genetic factors in determining whether some people are at risk of developing the disease, and what happens then they do.

The Arthritis Research UK Centre for Epidemiology is investigating the cause, progress and treatment response of musculoskeletal disorders with particular focus on inflammatory arthritis and osteoarthritis.

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