In this guest post, Natalie Carter, Head of Research Liaison and Evaluation at Arthritis Research UK, looks at the findings of a new article published today in Arthritis Research &Therapy and tells us more about the latest developments in rheumatoid arthritis research.
Rheumatoid arthritis is an autoimmune disease that affects around 400,000 people in the UK alone. The disease causes inflammation in the synovium; a capsule that surrounds the joint, helping to keep the joint and synovial fluid – which is important to keep the joint lubricated – in place. The result of this inflammation is redness, swelling, the production of extra fluid, and pain in the joint.
The development of biological therapies
Although there is currently no cure for rheumatoid arthritis, there are a variety of treatments which can slow down disease development and keep joint damage to a minimum. There is also evidence that exercise can help with symptoms and keep joints flexible and mobile.
Drugs for rheumatoid arthritis include painkillers, steroids, non-steroidal anti-inflammatory drugs (NSAIDs) (for example ibuprofen) and disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate, which act by targeting the causes of inflammation rather than just simply treating the symptoms.
In recent years, a new class of drugs called biological therapies have also become increasingly used for treatment. One of the most well-known is anti-TNF therapy, which was pioneered at the Arthritis Research UK-funded Kennedy Institute in the 1990s (and recently written about on this blog).
Unfortunately, anti-TNF therapy does not work for everyone. Around 40% of patients who are prescribed these drugs either cannot tolerate, or do not respond, to this type of treatment.
The research presented in the article published today in Arthritis Research & Therapy starts to unpick the underlying reasons that could explain why some people respond well to TNF-α inhibitors therapy whilst others will see minimal or no benefit.
Who will respond to which treatment?
Clinicians already know that people with rheumatoid arthritis are very diverse – not just in terms of how severe their joint pain is, but also in the range of symptoms they experience, as well as how well treatments work for them. Importantly, the severity of inflammation is not always a good indication of which drug will work best.
The current method of prescribing is trial and error – when one therapy fails, another is tried. In order to avoid putting people on expensive medications which may not work, researchers are looking at ways to predict who will or will not benefit.
The race is on to find biomarkers that will be able to predict whether someone will benefit from biological therapies. Studies have been conducted investigating a number of genes and proteins, as well as metabolites present in urine and even brain activity. This area of research is in the early stages but some of these have shown real promise and may eventually allow doctors to tailor treatment to the individual patient.
The article published today contributes to this field by describing the differences in the synovial tissue in patients with rheumatoid arthritis.
The researchers investigated the synovial joint tissue and revealed that patients fell into four different subtypes. These subtypes were characterized by the presence of different amounts, patterns and types of immune cells found in the synovium.
Interestingly, one particular subtype that the authors called ‘myloid’ was associated with a good response to TNF-α inhibitors. Although this is a relatively small study of less than 100 patients this provides evidence that there is a group of patients who could be targeted with TNF-α inhibitors with a high success rate.
The article focuses not just on the synovial tissue within the joint but also on the molecules found within blood. This makes the information even more relevant to people with arthritis. Not everyone with rheumatoid arthritis will have a synovial biopsy, especially before they start treatment, however blood tests are easy to perform, less invasive and can be routinely analyzed.
The authors analyzed serum samples (derived from blood) to see if they could correlate biomarkers with the subtypes seen in synovial tissues, and more importantly to a patient’s response to biological therapy. Tantalizingly, they identified two markers that have potential to be used as a way of identifying patients that respond well to two different types of biological therapy.
One of the limitations recognized by the authors is that when evaluating the biomarkers identified, both in the blood and the synovium, it is not possible to interpret the information in a simple way. It is not a question of whether the biomarker is, or is not, present. In real-life, the situation is much more complex and there is a continuum between the different subtypes.
There is still a lot of research to be done before this can be used as a prognostic tool – but this is certainly a step in the right direction.
Stratifying treatment for rheumatoid arthritis
There is currently a lot of interest in the newly emerging field of stratified medicine in relation to rheumatoid arthritis. This essentially means grouping patients based on how they experience their condition, and how they respond to treatment.
The article published today focuses on biomarkers in the serum and the histology of the synovial tissue as ways of stratifying patients. However, Arthritis Research UK is funding research (such as the MATURA consortium which we have backed with £1m, in collaboration with the Medical Research Council’s stratified medicine initiative) into a number of methods that can be used to achieve stratification including ultrasound imaging, psychosocial factors, and genetic testing.
Rheumatoid arthritis is one musculoskeletal condition where stratification is likely in the future, as we already have a great deal of information on genetics, biomarkers and imaging. The prize for being able to stratify patients effectively is huge. It will mean patients get the very best, most effective treatment the first time. For people with rheumatoid arthritis this is particularly important as it avoids progressive joint damage and prevents permanent disability.
In addition, it makes treatment much safer for people with arthritis. Some drugs, such as TNF-α inhibitors have significant side-effects including bruising, bleeding, infections, and (in rare cases) allergic reactions. Stratification can be used to ensure that people susceptible to serious side-effects are offered an alternative treatment.
Finally stratified medicine has the potential to save healthcare systems like the UK’s NHS a considerable amount of money, and in a time of austerity this is a powerful argument.
That said, the application of stratified medicines to arthritis is not without its challenges. Measuring the success of treatment is a complex task for rheumatic conditions, as opposed to other conditions where remission rates or survival are more easily measurable. The future of research into arthritis and other autoimmune diseases will be focused on finding an improvement in symptoms rather than curing a condition.
We also need to think carefully about a number of social and ethical issues around this approach to treatment– for example, how might patients feel about only receiving treatment if they have a certain genetic makeup?
It seems clear though that the continued efforts of research in this field will benefit patients, uncovering more effective and robust ways of diagnosing the disease, administering treatments and preventing the on-going effects.
If you would like to find out more information about the research that Arthritis Research UK funds please visit www.arthritisresearchuk.org/research