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Rheumatoid arthritis is a disease affecting more than 21 million people worldwide.
Until just a few decades ago, people with rheumatoid arthritis had to resign themselves to a distressing loss of quality of life, with constant pain and an increasing loss of mobility as the disease progressed.
Roche’s commitment to understanding the causes and mechanisms of rheumatoid arthritis has contributed towards revolutionising treatment. Today, new biopharmaceutical therapies have made significant progress by effectively treating this disease and inhibiting joint damage and pain. The tools we are developing for quick diagnosis may also permit much earlier treatment in the future.
The exact cause of rheumatoid arthritis is still unknown, and as yet there is no cure, but our research continues and remission, where the disease goes into long-term hibernation, has become a realistic objective.
We have a rich history of medical innovation in this field and a promising future with our focus on personalised healthcare - an approach that specifically takes into account emerging knowledge about the molecular pathology of diseases and people’s individual characteristics.
Despite a great deal of research, the actual reasons why people develop rheumatoid arthritis remain unknown. The possible causes can broadly be divided into, those factors which are inherited and those factors which are encountered in our environment.
There is a tendency for rheumatoid arthritis to run in families. If one of a pair of identical twins has rheumatoid arthritis then the other has a 16% chance of developing the disease. This is substantially higher than the risk in the general population, which is approximately 0.8%.
Since identical twins have identical genes, the presence of the same traits in both twins exists and this high degree of what is called 'concordance', points to a major genetic contribution to the cause of rheumatoid arthritis. Yet, no single gene has been identified as the certain cause for the development of rheumatoid arthritis.
Similarly, there is no single environmental factor which is sufficient, by itself, to cause rheumatoid arthritis. However, throughout the world, rheumatoid arthritis is more common in women than in men. This suggests that hormonal factors may play a part in the development of the disease.
There has always been a widely held belief that rheumatoid arthritis is caused by an infection, but researchers have been unable to identify this as a cause. In a substantial proportion of cases, rheumatoid arthritis begins within a few weeks of an infection of some sort.
The risk of developing rheumatoid arthritis is higher in smokers. People with rheumatoid arthritis who continue to smoke are also more likely to develop what is called extra-articular disease (nodules, involvement of the lung or inflammation of the blood vessels).
In people with many of the genetic risk factors for rheumatoid arthritis, exposure to a single environmental risk factor may trigger the disease. However, in the majority of people these factors (and others which have not yet been identified) probably act cumulatively, slowly lowering the threshold for the development of rheumatoid arthritis.
Roche researchers have helped to drive advances in our knowledge of rheumatoid arthritis with their investigations during the 1990s. This research has already resulted in the discovery of innovative new therapies and potential therapeutic targets. Today, we continue to deepen our understanding of the immune system and rheumatoid arthritis with the aim of fulfilling our ambition of developing even more personalised solutions to tackle the disease.
Rheumatoid arthritis is a chronic, inflammatory autoimmune disease, where immune cells mistakenly attack and destroy healthy body tissue, because they believe the healthy tissue is a bacteria or virus. It is incurable and progressive.
Rheumatoid arthritis is characterised by inflammation of the synovial membrane, which lines the joints and is essential for the protection and lubrication of the bone and helps to ensure joint mobility. Inflammation occurs because the immune cells, which are designed to protect the body, start to attack the joints. The inflammation spreads to the cartilage or bone causing pain, stiffness and swelling, and may eventually result in irreversible bone destruction.
The disease affects people of all ages and of both sexes, but women are three times more likely to be affected than men and often first symptoms develop around the age of 40.
The destruction of joints can begin shortly after the first symptoms, so early diagnosis and treatment is vital. Affected joints can be painful, hot, red, swollen and stiff, and progressive restriction of movement can occur, while other common symptoms include fatigue, morning stiffness, muscle aches and loss of appetite.
In many cases it is only after a short time that any movement of the limbs causes pain, making simple everyday tasks difficult, such as opening a jar or making tea.
Rheumatoid arthritis is also a systemic disease, which, although not the case for everyone, means that it can affect the whole body and internal organs such as the lungs, heart and eyes.
In addition to progressing quickly, rheumatoid arthritis may involve both periods of remission and disease flare ups. For people with rheumatoid arthritis, disease flares can cause further joint destruction, and therefore a key aim of treatment is to tightly control the activity of the disease through regular monitoring.
The prognosis for some people with rheumatoid arthritis can be poor, and only a year after diagnosis, one in seven people are no longer able to work. The impact of the disease is shown by work ability figures: after five years 40% of people lose their jobs because of rheumatoid arthritis, three quarters of whom for reasons directly related to their arthritis.
The final stage of rheumatoid arthritis, characterised by severely deformed wrists and ankles, has become less common due to advances in the diagnosis and treatment of the disease.
Roche’s scientists are acutely aware of the daily challenges faced by people with rheumatoid arthritis and the clinicians who care for them, and because of this we strive to discover and develop even better diagnostic tools and therapies.
Currently doctors rely on a range of signs and symptoms to make a firm diagnosis of rheumatoid arthritis. They conduct a physical examination, run laboratory tests and examine the patient’s history. However, by the time these signs are obvious many people are already losing mobility in their damaged joints. The ideal time for starting treatment may also have passed; the earlier treatment is started, the better the disease can be controlled.
Novel molecular diagnostics now offer a way out of this dilemma by speeding up effective diagnosis.
Roche is helping to transform the diagnosis of rheumatoid arthritis by providing a laboratory test for antibodies to cyclic citrullinated protein (anti-CCP) in blood. Anti-CCP is highly specific to rheumatoid arthritis, so it helps to confirm a diagnosis and can predict the eventual development of rheumatoid arthritis if the patient has arthritis.
Roche’s specialist tests arm doctors with information, enabling them to decide on the best treatment as quickly as possible.
Increased understanding of rheumatoid arthritis and progress in biotechnology have revolutionised treatment over the last couple of decades.
Traditionally, treatment was based on large-scale suppression of the immune system (immunosuppression) and the use of anti-inflammatory agents. Doctors still use a range of these treatments – often in combination with each other or with newer treatments.
They include disease-modifying anti-rheumatic drugs (DMARDs) - non-specific immunosuppressive drugs intended to combat the signs and symptoms of rheumatoid arthritis and slow down joint destruction. Glucocorticoids (corticosteroids) counter inflammation, but side-effects limit their use. Non-steroidal anti-inflammatory drugs (NSAIDs) can be used to manage the signs and symptoms of mild rheumatoid arthritis.
In the 1990s, researchers acquired ever more knowledge about rheumatoid arthritis and other autoimmune diseases. At the same time, advances in gene technology provided medicine with a completely new class of substances, namely biopharmaceuticals.
The result was new treatments that act on the processes involved in the disease, making it possible to stop or at least slow its progression. Roche’s research led to the discovery of innovative new therapies that target the key drivers of inflammation. Roche continues to lead the way by developing biopharmaceutical treatments with different modes of actions that offer alternative options to physicians and people with the disease.
The progress that has been made in diagnosing and treating rheumatoid arthritis in recent years lays the foundations for even more exciting developments in the future.
In the diagnostics field, Roche’s goal is to enable rheumatoid arthritis to be detected earlier through a reliable disease indicator in the form of a biomarker incorporated in a diagnostic test. Our hope is that biomarkers will be able to recognise the disease within weeks, or even days, so that treatment can prevent joint damage.
In terms of treatment, biopharmaceuticals now provide direct access to the many different sites at which it might be possible to intervene in a malfunctioning immune system. Progress is being made at an ever increasing rate and a decisive turning point in treatment is now in sight.
Roche already believes the goal of remission - the point when all or most of the patient’s symptoms of the disease have gone away and further damage to the joints has stopped - is an achievable target.
Other new forms of treatment in development at Roche include a molecule that inhibits the inflammatory process and a therapeutic antibody that directly inhibits bone destruction.
The challenge is to have available a range of therapies that act at different sites in the immune system. In the long run we want to be able to identify the appropriate component of the immune system in each individual patient to enable effective treatment to start as soon as possible.
We hope that one day biomarkers (indicators that assess the biological state of an organism) will be able to predict which drugs are most appropriate and likely to work in a particular patient, depending on their genetic predisposition, lifestyle and environmental conditions, and what dosage will have the greatest effect.
Our goal is to use modern technologies to provide more powerful diagnostic tools and even more effective and targeted biopharmaceutical treatments for rheumatoid arthritis.
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