Arthritis Today - Autumn 2009

We’ve known for a long time that obesity is bad for us, but a new Arthritis Research UK report reveals that very overweight people are a staggering 14 times more likely to get osteoarthritis of the knee than those in a healthy weight range.

Tram conductor Dean Collier was forced to give up work five years ago after starting to suffer from severe pain in his knee, diagnosed as osteoarthritis.

Tall at 6ft 2ins, but at 17 stone Dean was also classed as overweight. As the pain from standing for long periods of time was becoming unbearable, Dean was moved to driving the trams and later to an engineering role, but when the pain got so bad Dean had to give up work, and was treated for depression.

But an appointment with a nurse at his local GP surgery signalled a new start when Dean, from Nottingham, was advised to attend a local exercise programme. The one-hour circuit training classes were held twice a week at his local leisure centre, and combined with regular swimming, and cutting out fizzy drinks, chocolates, sweets and cakes, he soon lost a stone.

“It was difficult at first, but after a few weeks the exercise and good diet came naturally. It was a complete lifestyle change and the change was incredible,” says Dean, now 42. The pain in his knee reduced, became less stiff and aching, and more flexible.

Dean is just one of millions of people in the UK for whom weight is a serious issue. The rise in obesity and the resulting increase in the number of people suffering from osteoarthritis - particularly of the knee - as a result, has prompted Arthritis Research UK to produce a new online publication to warn the public of the hitherto little publicised dangers to their health and quality of life of obesity.

In fact, obese people are four times more likely to develop osteoarthritis of the knee as they are to develop high blood pressure or type-2 diabetes.

But whereas high blood pressure and diabetes may be substantially improved on losing weight and are relatively easy to control with therapy, the changes resulting from osteoarthritis are irreversible, as worn cartilage cannot currently be repaired.

However, according to Professor Alan Silman, Arthritis Research UK medical director, there is good news for the obese and overweight whose knees become painful due to osteoarthritis as a result of their weight. “Research shows that losing weight, however modest, when combined with exercise, is a panacea at every stage,” said Professor Silman.

“Achieving a healthy weight reduces the risk of developing the disease in the first place, relieves existing symptoms and helps to prevent further deterioration. And weight loss with exercise has been shown to achieve the same level of symptom relief as joint replacement surgery.”

Osteoarthritis has been, if not ignored, then certainly underestimated
 
Arthritis Research UK is concerned that while rising rates of obesity have been linked to a number of serious disorders and health concerns, the risk of potentially crippling osteoarthritis has been, if not ignored, then certainly under-estimated.

The true impact of obesity in the development of knee osteoarthritis has only recently become clear, said the charity, pointing to a study which revealed that at the most extreme, very obese people with a body mass index (BMI) of 36 or more have a 14-fold higher risk of knee osteoarthritis compared to those in the healthy BMI range.

Professor Silman warns there was a real concern that unless rocketing rates of obesity were tackled, the numbers of people needing joint replacement surgery would soar, which would have a considerable impact on the NHS.

“There are two major risk factors for developing osteoarthritis – ageing and obesity – and as both these factors are on the rise in the UK, it’s an obvious prediction to make that the outcome could be a massive cost to the health service,” he adds.

Joint replacements are more likely to fail earlier in obese patients, and the heavier the patient the less likely it is that surgery will bring about an improvement in symptoms.

Very obese women are 19 times more likely to need knee replacement and four times more likely to need hip replacement surgery compared to women of a healthy weight.

A series of studies has shown that even modest weight loss and exercise can help to reduce not only pain but also mobility and the ability to perform everyday activities.

Certainly Dean Collier can vouch for the difference exercise and weight loss has made to his quality of life – and to his knee pain. “I feel so much more positive, and I’m planning to carry on exercising and eating healthily – in the hope that I can lose even more weight,” he says.

For 30 years Bev Davis has been living with the debilitating effects of rheumatoid arthritis (RA) – and particularly with the intense fatigue that is part of the condition.

“It’s absolutely draining, to the extent that all you want to do is to lie down,” says Bev, now 48. “Even reading is too much. You become mentally and physically blocked, and it’s all you can do to lie on the sofa and watch the telly. It brings you down so much because you can’t plan to do things.”

For Bev the fatigue is worse when her RA is in flare, and she has learned over the years to try to pre-empt its onset. “What I try to do is to pace and plan my day, and to allow myself rest periods. I try and conserve energy if I know I’m going to be doing something,” she explains.

Bev, from Portishead, near Bristol, had the worst time of it when her three now grown-up children were young.  “Just taking them to school or doing the shopping was exhausting. Now they’re grown up it’s slightly easier to plan my life, but for 20 years just the thought of going out in the evening with friends was impossible. I’d make the tea then flop down on the sofa and that would be it. Fatigue has had a huge impact on my life and on my social life. I’ve talked about it with other people with RA and we have a term for when the fatigue is really bad – we call them ‘wipe-out days’ when you simply cannot do what you planned to do.”

Fatigue associated with RA is very different to normal tiredness.Up to 90 per cent of people with RA experience fatigue, 40 per cent on a daily basis, but until recently, this element of the condition had been largely ignored and insufficiently taken account of by medics.

Both patients and clinicians agree that fatigue associated with RA is very different to normal tiredness.

“It’s different in intensity, it’s unpredictable, it’s not earned and it’s unresolvable, appearing to serve no useful purpose,” explains Professor Sarah Hewlett, an expert on fatigue in RA, and Arthritis Research UK Professor of Rheumatology Nursing at the University of the West of England in Bristol. “You can’t refresh yourself through rest or sleep. And the consequences of fatigue permeate every sphere of life, with far-reaching effects on physical activities, emotions and relationships.

“We know that fatigue features in most long-term conditions, and RA is no different,” adds Professor Hewlett. “However, in multiple sclerosis, for example, patients say their fatigue makes the symptoms worse but in RA it’s the other way round, and the RA symptoms seem to make the fatigue worse.”

Attitudes to fatigue are now changing, partly because Arthritis Research UK is is taking it very seriously indeed. At a special workshop convened by the charity last year, experts from a range of related areas met to discuss the need to know more about fatigue in RA and as a result a taskforce has been drawn up looking at how it can be dealt with more effectively.

“A recent survey of rheumatology nurses showed that they want to treat fatigue better but the problem is they don’t know how to measure fatigue or how to manage it,” says Professor Hewlett, who is heading the Arthritis Research UK taskforce.”What we are hoping to achieve through the taskforce is to identify and review the evidence for  existing types of treatment and management of RA fatigue and then summarise the key questions that should be addressed by future research.”

One question that is bound to feature prominently is what causes fatigue in RA, although the answer is of course more complicated than the question.

It’s likely that a combination of factors is responsible: biochemical, as a result of inflammation and/or anaemia; physiological, due to muscle weakening or poor sleep; and psychological, linked to stress, anxiety, and depression.

“The causes might differ from patient to patient, but also between patients over time, so that one week it could be caused by inflammation, and another week it could be down to your psychological state of mind,” says Sarah Hewlett.

“Some of our research is identifying different types of fatigue which may provide us with some knowledge of the different pathways of fatigue and different predictors. So a short-term predictor might be how active your disease is today, and how well you slept; whilst in the long term, fatigue might be related to joint damage or a history of depression. Once we find out, we can develop some appropriate ways of dealing with it.”

Experts stress that the aspiration is currently to manage fatigue, not to get rid of it entirely. Depending on the causes of an individual’s fatigue, various options are available; drugs such as anti-TNF therapy drastically reduce fatigue in many patients with RA (but not back to normal levels and they are not a recommended treatment for fatigue), and exercise, and cognitive behavioural therapy (CBT), which addresses thought and feelings and their link to behaviour may be helpful. An Arthritis Research UK-funded clinical trial in Bristol is currently looking at whether a six-week self-management course involving CBT is more helpful to RA patients than just handing them an Arthritis Research UK leaflet on looking after joints and managing fatigue.

“During the course we talk to patients about difficulties they might have sleeping, which is a big issue for some people but not others, about stress, and we help them with achievable goal-setting and get them to list activities such as “drainers” and energisers” - activities that tire them or give them energy,” explains research associate Celia Almeida. “Some activities, such as exercise or gardening, fall into both camps, depending on how people are feeling. Patients are encouraged to channel their frustration and anger into positive action, learn to establish some ‘me time,’ and how to set priorities for the limited amount of energy they have.”

The clinical trial is not due to finish until the end of the year, and results will not be published until next year, but Ms Almeida says that so far the informal comments from the patients receiving CBT has been  positive. “There’s a sense that the course has been life-changing for a lot of people.”

Part of the benefit, she believes, is that the course acknowledges that fatigue is important to patients and is a major factor in RA, hitherto under-recognised by rheumatologists. However, according to Sarah Hewlett, that view is now becoming outmoded.

“We’re getting there in terms of fatigue being taken seriously, and this has largely been driven by patients,” she acknowledges. The fact that an international consensus has now been reached that fatigue should now be measured in all RA clinical trials is a major step in the right direction, as unless ways are found to accurately measure fatigue it cannot be adequately dealt with.

Bev Davis agrees that rheumatologists are now more understanding of fatigue than in the early years of her disease. For the past eight years she has been a patient partner at Bristol Royal Infirmary, and her role is to give the patient’s view on all research projects that are being set up.

She is delighted that fatigue in RA is being addressed.”It’s so debilitating,” she says. “It’s hard to explain to people that you’re not just being lazy, and to say to them: ’hang on, it’s the illness; it’s not me.’ ”

Arthritis Research UK’s fatigue and RA taskforce is due to report back at the end of the year.

For Jan Williams, gaining a First Class Honours degree in Fine Art earlier this year was the happy ending to her incredible story of triumph over illness and disability.

For years Jan, from Cardiff, was crippled by severe psoriatic arthritis. Frequently in and out of a wheelchair, she struggled to bring up her five children, and had to give up work in her 30's when her condition worsened. For several years her arthritis. was not properly controlled and she had to live with constant pain and restricted mobility.  In particular her hands were inflamed and deformed by the devastating effects of the disease.

But six years ago her life turned round. A new drug therapy transformed her life, enabling her to pick up a paintbrush for the first time since leaving school and enroll on a degree course in Fine Art at Cardiff School of Art and Design.

Jan’s salvation was a drug called infliximab, part of a new class of drugs called anti-TNF therapy. The drugs were pioneered and developed by Arthritis Research UK whose Cardiff branch Jan has been a member of for several years. The drugs also known as ‘biologicals’, block the action of a protein called tumour necrosis factor (TNF), excessive amounts of which cause inflammation when they build up in the joints and bloodstream. Although not a cure, they control symptoms in many patients to such an extent that they can return to a near-normal life.

Now Jan’s hard work and artistic flair has been rewarded after she gained a First Class honours degree – and in the same week one of her paintings of her studio was selected from amongst all final year painting students for a £500 prize by the National Museum Wales. Her painting is now hanging at the Cardiff School of Art and Design Howard Gardens campus.

“My hands are quite twisted and deformed by arthritis so I wore gloves at my art school interview because I didn’t want to be treated differently”, says Jan. “The past three years have been brilliant. Going to art school and winning this prize has been a wonderful experience, but if I hadn’t had arthritis I would never have done it. Infliximab has made a complete difference to my life and enabled me to do things I didn’t know I was capable of.”

Jan was encouraged to take up the Fine Art degree by her consultant at University of Wales Hospital, Dr Sharon Jones, to boost her self-esteem, which was low after years of illness.

“I was inspired to do Fine Art through the stories of the Great Masters such as Renoir, Klee and Dufy, all of whom produced great and enduring works of art despite suffering crippling illnesses like mine,” explains Jan. “I also wanted to study art because I felt it would be a way for me to fight back and restore my self-esteem and independence.”

Although she had not done any art since junior school, Jan sailed through the access course before applying to art school where she has specialised in painting interior scenes in oil on board and canvas.

In a way, gaining a degree has been the beginning rather than the end of her story because she is now studying for a Masters in Fine Art, and as a result of winning the prize she has been asked to produce paintings to hang in the rheumatology department at the University of Wales Hospital where she is a patient.

Director of learning and programmes Professor Mike Tooby, who selected Jan’s painting to win, said he was touched by the simplicity of Jan’s painting. “The one I selected for the prize was one of a group that Jan had painted of her studio, and they were very beautifully achieved and very delicately judged,” he said. “There was a very clever use of light that filled the space, and crucially, the studio was empty - in contrast to many degree show paintings which tend to be very busy. In retrospect, now I know a bit more about Jan and her situation it makes the delicacy and light in her paintings really touching.”

Fred Johnson, area appeals manager for Arthritis Research UK Campaign in South Wales, said: “Jan’s achievement is an inspiring one, which will help other people with severe arthritis to realise that the outlook for them is more positive than ever before. We are very proud of anti-TNF therapy as it has truly revolutionised treatment for millions of people with inflammatory arthritis not just in the UK but around the world.”

Anti-TNF therapy, developed by scientists at Arthritis Research UK’s Kennedy Institute in London, is effective in many different types of severe inflammatory arthritis, including rheumatoid, psoriatic, juvenile idiopathic, and ankylosing spondylitis. The therapy has generated Arthritis Research UK more than £30m in royalty payments over the past nine years, and two new anti-TNF drugs, certolizumab pegol and golimumab, should soon be licensed for use in the UK.

When it comes to osteoporosis research, there are only three centres in the world rated higher than Sheffield University – the University of California, Harvard and Yale in the US – so it’s in exalted company.

Sheffield is unusual in that its clinical research spans bone diseases from the very young to the very old, encompassing not just osteoporosis but also the childhood form of brittle bone disease osteogenesis imperfect and bone cancers.

Its clinical research, widely supported by Arthritis Research UK in recent years, is underpinned by a basic biomedical research, which has now been brought together in a single unit and involving five departments within the medical school. The Mellanby Centre was opened earlier this year by two former alumni of the university renowned for their glittering careers in bone biology research UKh, Professors Jack Martin and Graham Russell.

While the Mellanby Centre, with its labs and high-tech equipment, will concentrate very much on basic science, Professor Croucher, joint centre director with Professor Richard Eastell, stresses that they want to develop new approaches to treating bone diseases, and to translate research discoveries via the new National Institute for Health Research-funded Biomedical Research Unit for Bone at the Northern General Hospital in the north of the city.

"Two of our main aims are to translate advances in research into benefits for patients, and to promote the profile of skeletal research in the UK," he says.

"There are many good groups of people working in many universities, but the advantage of bringing them together under one roof where they can talk to each other and share ideas.

"We want to bring together a lot of people with interests not just in arthritis and bone disease, but also in children’s bone diseases and bone cancers, and to try and learn the lesson from one disease and apply it to another. Sheffield is very strong on the bone cancer side and there are things we are doing in cancer research that can be applied to osteoporosis and osteoarthritis – there is a lot of potential for cross fertilization, and we would hope that would be of interest to Arthritis Research UK in the future."

Three researchers at the medical school are already receiving funding from Arthritis Research UK in pursuing very different research agenda. Dr Alison Gartland, lecturer in bone biology, is now based at the Mellanby Centre, and has a new project grant to investigate bone and cartilage loss in inflammatory arthritis.

Currently, RA therapies designed to combat inflammation in RA aren't always effective in all patients and can have serious side effects. These drugs typically block the inflammatory chemicals that destroy joint tissue but at the same time also shut off the body's ability to fight infection. New targets and treatments are needed that utilise a more subtle approach to the problem and understanding the detail of the molecular mechanisms involved in inflammation should help to achieve this.

Dr Gartland explains: "We're looking at a receptor called P2X7 that's just one of hundreds of receptors present on the surface of cells all over the body. It's present on bone and cartilage cells and may be important in regulating the joint tissue destruction that occurs in rheumatoid arthritis (RA).

Receptors are special responsive areas that can be activated by chemical signals. Once activated, the cell starts to produce molecules that affect the way the surrounding tissue works. It's a bit like pressing a button and switching on a production line inside the cell. In the case of P2X7, we know that it's involved in inflammation but we don't know what it does to the actual cartilage in a joint. We're investigating how this receptor works in healthy joints so that we know what aspects of its activity are important for normal function."

The P2X7 receptor also exists in different forms, or "polymorphisms", depending on its genetic make-up. Dr Gartland and co-workers have found that in women with the normal fully functioning P2X7, bone loss is less severe than in women with the polymorphic receptors.

"This suggests that the severity of disease may be linked to the polymorphisms," she says. "If patients with polymorphisms experience more severe bone loss, we could screen for this genetic difference. Individuals who are positive for these polymorphisms could then be given treatments to prevent or slow bone loss at a much earlier stage, before irreversible damage has occurred."

The test would be part of a profile of prognostic tests to help assess risk of disease development. Therapies are already available to inhibit these receptors and this test may be useful to predict which patients will and won't respond well to therapy, and direct treatment accordingly.

As well as aiding prognosis and disease management strategies, the results of this research should benefit other musculoskeletal diseases such as osteoporosis and osteoarthritis.

The development of anti-TNF drugs represents a considerable breakthrough in terms of arthritis therapy. Tumour necrosis factor, or TNF, is an inflammatory chemical that's normally produced to protect the healthy body against infection. However, in RA, TNF production is continuous, and chronic pain, swelling, and eventually joint damage results. 

Epigenetics (meaning "over" or "above" genetics) is a rapidly advancing area of research that is changing the way we understand disease processes. We may be born with a set of genes that programme our bodies but the activity of these genes is influenced by epigenetic factors.

These factors often work as simple on/off switch mechanisms: all our cells carry the same genes but only specific ones are "active" or expressed where they are needed. Pancreatic cells, for example, produce insulin but kidney cells don't. The insulin producing genes are switched on in the pancreas but switched off in the kidney.

Professor Wilson comments: "Epigenetics play an important role in the development of human disease, including arthritis and cancer. In RA it may influence how severe the disease is and how patients respond to treatment. But the system is very complex - there are hundreds of thousands of epigenetic variations that switch genes on and off in different combinations. If we can find out how epigenetics affects the production of chemicals like TNF we might be able to devise new therapies to regulate this, and dampen down the aggressive nature of the disease."

Epigenetic markers can be measured and by comparing them in healthy individuals and individuals with RA, the ones responsible for different effects, like the overproduction of inflammatory chemicals, can be identified.

"We've already found a small difference in one of these markers that is linked to the production of IL-6, a major inflammatory molecule," says Professor Wilson, "and increased epigenetic markers are associated with higher TNF production."

The epigenetic marks on the TNF gene change with age as does the risk of developing RA. Could this marker be a predictor for RA risk or severity? If so, this could be a very useful clinical test to help disease prognosis, guide treatment, and predict treatment outcomes.

Tendons are tough, flexible pieces of tissue that attach muscle to joints and convert muscle force into skeletal movement. Damaged tendons lose their stretch and flexibility, causing considerable pain and immobility. The healing process is difficult and lengthy because the underlying tendon fibres don't always repair properly and patient quality of life is reduced.

Research aimed at improving tendon repair is difficult because studies rely on cell cultures grown in laboratory conditions and these don't model the real life situation very well. However, a revolutionary new research tool is about to change the way that we view tendon repair.

Dr Dawn Walker, Research Councils UK Fellow and lecturer in the Department of Computer Science, is attempting to create a "virtual tendon" using sophisticated computer simulation technology, with funding from an Arthritis Research UK project grant.

Dr Walker, a physicist by training, has extensive experience in the application of computer simulation technology to living tissue systems. She has successfully developed models for other tissue types and will adapt some of the software from these projects for use in the current project.

"Tendon isn't the most popular tissue to research" she says. "In the media, the heart or brain are much more interesting areas of development. The "virtual heart" project hit the headlines some years ago and is now proving to be an extremely valuable model for cardiac research projects. However, tendon problems are very common and cause immense suffering - we really need to address this disease area and improve predictive outcomes and treatment methods."

The project combines established knowledge of tendon structure and tissue dynamics with information from current laboratory research projects studying the effects of damage and repair in living tendon cells.

"All the data is integrated into the programme", says Dr Walker. "We know how tendon is constructed in healthy tissue and what happens to it when it's subjected to the stresses and strains of exercise, overwork and injury. It's important that we develop the model by testing it at every stage against real laboratory data to be sure that our model mimics the real life situation and is relevant to patient outcomes."

Once the model is up and running, any combination of parameters can be altered to represent different patient types and tissue damage, and the outcomes assessed. Eventually, the project aims to use the virtual tendon to inform therapy options and assess outcomes.

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 four 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.

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.

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!

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 six 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 isn't 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.”

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.”