New directions in arthritis research

Callum August 15, 2013 0
New directions in arthritis research

Penny Bould finds out how leading arthritis specialists are calling for more investment in longer rehab programmes, and how groundbreaking research into the condition’s causes is potentially opening up whole new avenues…

According to Cedars Sinai Medical Centre in the USA, arthritis is a term that actually encompasses around 100 conditions. Along with back pain and other musculoskeletal disorders, it’s the biggest cause of physical disability in the UK, resulting in challenging lives and untold human distress – as well as costing individuals and the larger economy billions of pounds.

Osteoarthritis is the most common form of arthritis in the UK, affecting around eight million people, and occurs when cartilage at the end of bones wears away, leading to joint pain and stiffness. The second most common is Rheumatoid arthritis (RA), which affects 0.8% of UK adults. Some people – like my own older sister Jackie, who now has difficulties writing – live with both.

There are many myths regarding arthritis, including the suggestions that it only affects older adults, and that there is nothing you can do about it if it hits you. Yet small children can get juvenile idiopathic arthritis; for many patients, their condition can be managed to improve their quality of life, whilst others experience pain so severe that they can lose consciousness, need help dressing and cannot work.

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More rehab, less cuts
In a recent global study carried out as part of pharmaceutical company AbbVie’s ‘RA: Join the Fight’ initiative, it was revealed almost two thirds of rheumatoid arthritis (RA) patients in the UK don’t feel that their conditions are well managed. Just over a quarter said they have a disease management plan in place, compared to 56% globally, prompting calls for increased collaboration between doctors and patients.

Professor Anthony Woolf, Professor of Rheumatology at the Royal Cornwall Hospital Truro and University of Exeter Medical School wants to see greater availability of rehabilitation programmes for people living with arthritis.

He told me, “If someone is not working, just reducing their benefits is not going to help them be more independent and return to work. We need access to rehabilitation and some flexibility from employers too.”

It’s a call that’s echoed by Disability Rights UK and a number of other disabled people’s organisations campaigning against benefit cuts. In terms of investment, Woolf’s view is that, “Musculosketal conditions [MSCs] seem to be ‘the Cinderella at the ball’ but we need to make them ‘the Princess’.”

Empowering Patients
Woolf is also Coordinator of – the European Musculoskeletal Information and Surveillance Network, which brings together 100 professionals across Europe with funding from the EU and the European League Against Rheumatism (EULAR). As he explains, “The project addresses the prevention and management of MSCs involving a network of institutions, researchers and individuals in 22 organizations across 17 countries.”

Woolf and colleagues want to empower people: “We want to put information in the hands of patients so they know what to expect, and also to have ways of checking if this is being delivered.” The key message for the public and healthcare professionals is that swift diagnosis and aggressive treatment – as Woolf points out, especially for those with RA – is the most effective way of minimising the impact for most patients.

Meanwhile, a large number of groundbreaking research projects are seeking to improve people’s lives, using advances in computing power to study genetics and identify which lines to follow.

PX 112516154Risk reduction
RA can be treated with many different types of medication, including the following:

– Disease-modifying anti-rheumatic drugs (DMARDs)
– Non-steroidal anti-inflammatory drugs (NSAIDs)
– Biologics, which include anti-Tumour Necrosis Factor (TNF) therapy
– Steroids, which used to quickly reduce severe inflammation

Ian Bruce, Professor of Rheumatology at The University of Manchester and consultant at Central Manchester University Hospitals NHS Foundation Trust, has led research that looked into possible risk factors for the onset of RA.

Working alongside the Arthritis Research UK (ARUK) Epidemiology Unit, they followed over 25,000 people aged 40-79 and identified those who subsequently developed RA.
They found that smoking, obesity and diabetes all increased the risk of developing the condition, while drinking a small amount of alcohol and belonging to a higher social class were associated with a reduced RA risk.

Women with more than two children, but who breastfed for a shorter time, were also at greater risk – but you could live the healthiest life possible, and still have a chance of getting RA. ARUK’s Medical Director, Professor Alan Silman, advises taking appropriate exercise, avoiding obesity and not smoking. Following a Mediterranean diet might help prevent the onset of the condition, but is not thought to affect its progress.

“Our message for government, GPs and the public is that if you have signs of inflammation in the joints, and it comes on quickly, then get the right treatment.” Silman says, adding, “There is a challenge in the NHS, with budgets under threat. A lot of care can be given in the community, and it so important to have the right skills. There have been a lot of advances in some underpinning science, and in imaging that can see individual cells and watch them as they go about the repair process.”

“You have it for life – it can be for decades, and there is a lot of suffering. The sum total of human misery is considerable.

PX Professor Costantino Pitzalis MD PhD FRCP  alternative angle redcomputer image _IMG_0865

Professor Costantino Pizalis is co-lead on a genetic research project aimed finding out which RA patients best respond to which treatments

Cutting Edge
“There has been some major progress in genetic understanding – we can confidently identify 46 genetic regions definitely associated with RA. It is highlighting targets for biologic drugs to block a pathway involved in inflammation,” explains Anne Barton, Professor of Rheumatology and Research Lead for inflammatory arthritis in adults at the Manchester Musculoskeletal Biomedical Research Unit (BRU) – a National Institute for Health Research-funded unit that presently has 22 projects underway.

Barton is co-leading the £10m ‘Maximising Therapeutic Utility for Rheumatoid Arthritis’ (MATURA) project, alongside Costantino Pitzalis – Professor of Experimental Medicine and Rheumatology at Queen Mary, University of London.

The study is thought to be unique, in that it combines analysis of synovial tissue in joints (led by Pitzalis) and blood biomarkers (led by Barton). Barton and her colleagues have been awarded £2.5m of funding from ARUK and the Medical Research Council to research the genetic and genomic markers that can predict which RA patients will respond best to which treatment – otherwise know as a ‘stratified’ or personalised approach to treating the condition.

Pitzalis points out that RA is heterogeneous, and more complex than some people may think. “I am extremely excited about the study,” Pitzalis says. “It is involving 12 academic centres, with some 50 academics and clinicians, and nine industry partners. It will look at genetic and genomic approaches, using protein analysis to identify novel biomarkers. Understanding the mechanisms at work will help to potentially develop new drugs and maximise the therapeutic benefits for responders and non- responders, because some 40% of patients are difficult to treat.”

PX Iain McInness

Professor Iain McInness is heading up the research team at ARUK’s new Rheumatoid Arthritis Pathogenesis Centre of Excellence

In terms of other developments, Barton, notes that, “In the Netherlands there is a study looking at high risk patients with a family history who may carry antibodies. In the UK, Switzerland and France there are investigations into predicting and preventing who can get it. There’s [also] a lot of interest in using ultrasound to look inside joints to better manage it.” Another step forward has been the development of some drugs that can be self-injected.

The quest for the causes
Another piece of good news is that Arthritis Research UK – thought to be the largest medical research charity of its kind in the world, with a research spend of £28m in 2011-12 – has announced a major new research centre in the quest to discover RA’s underlying causes. The £2.5m Rheumatoid Arthritis Pathogenesis Centre of Excellence is a collaboration between the Universities of Glasgow, Newcastle and Birmingham, with all three committing to an additional £4m of funding over five years.

The researchers at the new Pathogenesis Centre will headed by Professor Iain McInness at the University of Glasgow. “They will focus on the mechanisms of auto-immunity that cause [RA] to start and why it doesn’t stop,” he says. “This results in chronic inflammation in the joints, which cannot be suppressed in at least a third of patients, despite treatment with modern biological therapies. There is no cure, and many people are still suffering. We now have a fantastic chance of doing something about it.”

pic01 RA normal jointWhat is Rheumatoid Arthritis?
RA is a serious, inflammatory, autoimmune condition that affects joints, tendon sheaths and the body’s internal organs, leading to chronic pain and fatigue. Its exact cause is unknown. Its onset is most common between the ages of 40 and 70 – but it can affect any adult from the age of 16 – and affects two to three times more women than men.

Researchers at Cedars Sinai Medical Center in the USA state that RA can be accompanied by a low grade fever. Small lumps may appear under the skin at pressure points, there can be inflammation of the tear and salivary glands, in the linings of the heart and lung, and in rare cases, the blood vessels.

pic02 RA ra jointAccording to the UK charity Arthritis Care, RA inflammation affects the thin synovial membrane that lines the joint capsule, tendon sheaths (the tubes in which the tendons move); and the bursae – sacs of fluid that allow the muscles and tendons to move smoothly over each other. The affected joints and inflamed tissues will subsequently become stiff, painful and swollen.

People’s symptoms might include feeling generally unwell and tired, and often stiff – particularly first thing in the morning, or after sitting still for a prolonged period. At times, the condition might be dormant. Because RA affects everyone differently, it can be hard to diagnose.

Case Study 1 – “Living with RA is evil at times”
At 18, Dizzy (who prefers not to be further identified) had just started working for a media organisation when a lump appeared on her ankle. She was subsequently diagnosed with RA.

Living with RA is evil at times, but most of the time it’s OK. My wrists were killing me using manual typewriters. I saw the way I was walking reflected in a shop window and I didn’t know what was going on. I felt I didn’t know who I was – I felt isolated, unfeminine and frightened, so I put off seeing a doctor.

My father had curvature of the spine due to ankylosing spondylitis, and I knew arthritis could be inherited. I went very thin, almost anorexic, trying to cope with the pain, almost in tears. Luckily I had a really good friend and consultant.

PX36611770I went through the ‘Why have I got this, why is it me?’ thing. I had therapy to help overcome certain things, and rediscovered my femininity when I got into a relationship. We’ve now been together 25 years.

Having a complete shoulder replacement changed my life. It meant that I could drive, do hobbies and be independent, without relying on other people. I had my knees replaced and full foot surgery too. I didn’t like the poking around, and people saying ‘poor you!’ – I hated that!

Wrist supports and an electric typewriter helped [at work], but I also had a very good boss who protected me, which I think you need, and also a very supportive mother. I saw faith healers and all that with my mother, almost for her. If you have a major disease it can make you feel you are almost too ill to do anything. I can now walk, but I fell over recently, reminding me how fragile I am.

It’s not going away, or going to get better. I have weekly anti-TNF injections in the stomach. Diplofenac pain killers help me, or I sleep it off. One friend said I am always trying to overcompensate – sometimes you have to give in to the illness. You have to adopt an attitude and stick it through before the painkiller kicks in.

I’m not someone who likes to ask others to do things. For example, I was on a photography course and reluctantly had to ask someone to switch a light meter on. You know you can’t physically defend yourself, and it’s said that I scrutinise people a lot – like [when] I’m on the underground, encountering drunk lads, or people not understanding why I need to ask for a seat.

Case Study 2 – “The thing that bothers me most is not being able to write properly”
My older sister Jackie, who is now retired, finds she is only aware of her hands being affected. She is, as Professor Anne Barton describes her patients, ‘stoical’, taking it in her stride without much complaint.

“I’ve not been to see a specialist for about five years, because he wanted me to take medication I felt was much too strong,” says Jackie. “I was concerned it could affect my liver, eyesight and trigger hair loss, so for me it was more restricting than the arthritis.

“The thing that bothers me most is not being able to write properly. Still, I have my computer, otherwise I don’t dwell on it. I don’t know if it will get worse or spread. I have my husband to open my jars and fill in forms. I suppose if I was working it would be more of a problem.

“I don’t suffer very much. You hear about people having a lot of pain, but all I have is an ache every so often. Still, your body gets used to things.”

Further information
A three-year EULAR-funded project aimed at improving and harmonising standards of care for RA and other musculoskeletal conditions across EU member states.

Arthritis Research UK
One of the world’s largest medical research charities, ARUK funds research into all types of arthritis and related conditions.
Contact: 0300 790 0400

National Rheumatoid Arthritis Society
Provides information and various support services for people with RA, families, friends, carers and health professionals
Contact: 01628 823 524 (general enquiries) / 0800 298 7650 (freephone helpline)

Arthritis Care
A user-led charity and campaigning organisation providing support to people with all forms of arthritis.
Contact: 020 7380 6500 (general enquiries) / 0808 800 4050 (freephone helpline)

RA: Join the Fight
A global initiative organised by pharmaceutical R&D specialist AbbVie, aimed at encouraging patients and doctors to develop effective RA management plans

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