Social relationships are just as important to health as other common risk factors like smoking, lack of exercise or obesity, new research shows.

Numerous studies have suggested that strong social ties are associated with better health and longevity, but now a sweeping review of the research shows just how important social relationships really are. Researchers from Brigham Young University reviewed 148 studies that tracked the social habits of more than 300,000 people. They found that people who have strong ties to family, friends or co-workers have a 50 percent lower risk of dying over a given period than those with fewer social connections, according to the journal Plos Medicine.

The researchers concluded that having few friends or weak social ties to the community is just as harmful to health as being an alcoholic or smoking nearly a pack of cigarettes a day. Weak social ties are more harmful than not exercising and twice as risky as being obese, the researchers found.

Notably, the strongest effect was shown when studies used complex measures of social integration, focusing on a person’s family ties, friendships and work connections. In those studies, the survival rates for people with strong relationships were twice that of those with weaker ties. Single measures, like whether a person was married or living alone, weren’t good predictors of health. For instance, people who lived with others had just a 19 percent survival benefit compared with those who lived alone.

Although research has long suggested social relationships are linked with better health, it hasn’t been clear whether the effect is due to the fact that healthy people are more likely to be socially active. A person with chronic health problems has more difficulty spending time at work and with friends. While the data collected from the latest analysis don’t prove a causal relationship between health and social ties, the researchers say it is strongly suggestive, because the people studied were otherwise healthy and followed for an average of seven-and-a-half years. Even when controlling for a person’s health status, the benefit of social relationships was still evident.

There are several theories as to why social connections may improve health, including that people with strong family and social ties may be more active, more likely to seek medical care and have lower stress. “Our relationships encourage us to eat healthy, get exercise, get more sleep, see a doctor,’’ said Julianne Holt-Lunstad, associate professor of psychology at Brigham Young.

Dr. Holt-Lunstad said the research suggests that medical checkups and screenings should also include measures of social well being. “Medical care could recommend if not outright promote enhanced social connections,” she said.

Drinking alcohol can not only ease the symptoms of rheumatoid arthritis it appears to reduce disease severity too, research suggests. Scientists at the University of Sheffield asked two groups of patients with and without the disease to provide details of their drinking habits. They found that patients who had drunk alcohol most frequently experienced less joint pain and swelling. Experts say this should not be taken as a green light for drinking more.

In the study, 873 patients with rheumatoid arthritis (RA) were compared to 1,004 people who did not have it. Both groups were asked how often they had drunk alcohol in the month running up to the start of the study. Patients completed a detailed questionnaire, had X-rays and blood tests, and a nurse examined their joints.

Dr James Maxwell, consultant rheumatologist and lead author of the study, explained the findings. “We found that patients who had drunk alcohol most frequently had symptoms that were less severe than those who had never drunk alcohol or only drunk it infrequently.”

X-rays showed there was less damage to their joints, blood tests showed lower levels of inflammation, and there was less joint pain, swelling and disability in those patients, the researchers found. They say they do not yet understand why drinking alcohol should reduce the severity of RA, and people’s susceptibility to developing it.

Dr Maxwell said: “There is some evidence to show that alcohol suppresses the activity of the immune system, and that this may influence the pathways by which RA develops. “Once someone has developed RA, it’s possible that the anti-inflammatory and analgesic effects of alcohol may play a role in reducing the severity of symptoms,” he added.

The authors say that further research is needed to confirm the results of the study and to investigate how and why alcohol has an effect on rheumatoid arthritis.

Previous studies have shown that alcohol may reduce the risk of developing the disease in the first place. Similarly, in the current study non-drinkers were four times more likely to develop RA than people who drank alcohol on more than 10 days a month.

A spokeswoman for Arthritis Research UK, which co-funded the research, said: “We would not want people with RA to take this research to mean that they should go out and start drinking alcohol frequently and in large amounts as this could be detrimental to their health.” She said some RA treatments, like the immunosuppressant drug methotrexate, can damage the liver when taken with large amounts of alcohol.

The patients in the study did not drink more than the recommended limit of 10 units of alcohol a week.

Although there is not yet a known cure for arthritis, there have been significant developments over the past couple of years that are paving the way for breakthroughs that may result in a world without arthritis. Here are the top ten.

1. New pathway for development of safe, effective medications for controlling inflammation in rheumatoid arthritis (RA).
An Arthritis Foundation-funded study at Brigham and Women’s Hospital in Massachusetts revealed a previously unknown mechanism that promotes inflammation in the joints of patients with rheumatoid arthritis (RA). It turns out that blood platelets, which are important for stopping bleeding, can enter joints affected by RA and form new structures called microparticles. These microparticles can affect the tissues’ lining, causing well-known characteristics of active RA including joint swelling, warmth and tenderness.

So what? The relevance of this finding for future treatment of RA is substantial. It shows a new way by which blood platelets impact inflammation, helps explain why some newer medications are sometimes not effective in treating RA, and opens up a new target for drug development.

2. Small reduction in body weight could mean better health for the joints.
It is well known that obesity has a strong association with osteoarthritis (OA), but it has been assumed that this association is due to the strain on joints caused by excess body weight. This study supports a different mechanism. Normally, fat cells secrete a substance known as leptin, which tells the brain that eating should stop. Using mutant mice that lacked the leptin receptor in their brains, researchers found that the mice kept eating as they became increasingly overweight. Surprisingly, these mice did not develop arthritis even in the face of marked obesity because cells in normal joint cartilage (chondrocytes) have the leptin receptor and can respond to leptin with changes in their metabolism in ways that promote OA. Therefore, the mutant mice have cartilage that is resistant to the effects of obesity that are mediated by leptin.

So what? This study supports the hypothesis that substances derived from fat tissue, such as leptin, directly harm articular cartilage and predispose individuals to the development of OA.

3. Radiographic features of osteoarthritis strongly associated with knee pain.
Pain is the major clinical symptom in osteoarthritis of the knee and a key reason for seeking medical care. Painful OA also limits activity, reduces quality of life and can lead to disability. Understanding how and why OA causes pain is a top priority for finding better ways to manage patients with OA. This study carefully demonstrates how radiographic findings correlate with pain in the knees of patients with OA. It shows that loss of joint cartilage correlates strongly with symptoms of pain, while bone spurs (osteophytes) were less likely to be associated with joint pain. Although researchers continue to search for information about how OA leads to pain in joints, this study certainly helps narrow the search.

So what? These findings are essential for improving our strategies to control the pain and disability caused by OA.

4. New diagnostic test for a rare form of juvenile arthritis.
The cytokine known as interleukin-1 (IL-1) is a central mediator of inflammation. It exerts its effects through activating the IL-1 receptor on many cells that are important in producing inflammation. The effect of IL-1 on this receptor is blocked by another molecule known as the IL-1 receptor antagonist, which helps the body avoid excessive inflammatory responses. This study describes the clinical findings in families in which a genetic mutation causes the IL-1 receptor antagonist to be ineffective. The affected patients had severe rashes, skeletal abnormalities, enlargement of the liver and spleen, and inflammation in internal organs that were apparent at the time of birth or shortly thereafter. Treatment with a drug designed to block the IL-1 receptor (anakinra) resulted in rapid improvement.

So what? These exciting clinical findings reveal a new diagnostic test for a rare form of juvenile arthritis. The study also sheds light on the interactions of substances in the body that promote and inhibit inflammation in the body. Balancing these interactions is important for all inflammatory diseases.

5. Crucial process in the development of the immune system illuminated.
T cells represent a very important part of our immune defense system. Like all other white blood cells, these cells are formed from stem cells in a life-long process. The transformation of stem cells into T cells is guided by mechanisms that precisely turn on and turn off specific genes. Understanding how this process is controlled is fundamental for understanding human biology and for applying stem cells to the treatment of a broad variety of human diseases. In this study, a protein referred to as NKAP is identified as a key regulator of the process that guides the transformation of a bone marrow stem cell into a T cell that can distinguish molecules of the person’s own body from foreign molecules, such as those on an invading pathogen. The experiments showed how NKAP is required for regulating a mechanism that permits cells to pick up signals in their environment through sensors on the cell surface and deliver those messages to the nucleus of the cell. These messages govern a specific set of genes required for T cell development, and are essential for development of a specific group of T cells known as alphabeta T cells. This study illuminates a crucial process in the development of the immune system.

So what? This insight is important because subtle abnormalities in the function of this process are likely to be associated with both cancer and autoimmunity. A full understanding of this process is also essential for making the best use of stem cell treatments for autoimmune diseases in the future.

6. Osteoarthritis involves specific metabolic and immune mechanisms that are amenable to pharmacological intervention.
It has long been accepted that rheumatoid arthritis (RA) is an autoimmune disease, a condition in which the immune system is attacking components of the body’s own tissues. In this study, the investigators used powerful new technologies to examine proteins from joints of patients with both RA and osteoarthritis (OA). Two important new findings emerged. First, it is clear that autoantibodies are present in patients with RA and OA and that these autoantibodies target different sets of self molecules in these two diseases. Second, fundamental structural elements of our genetic material deposit on the surfaces of joints and serve as targets for autoantibodies in patients with RA but not OA.

So what? Knowing the targets of autoimmune responses that cause tissue injury is essential for developing new approaches to manipulating the immune system to turn off specific unwanted autoimmune diseases (e.g., vaccines). The study also provides new insight into what is happening in joints of patients with OA – here is clear evidence that autoimmune responses occur in OA and may be amenable to pharmacological intervention.

7. Early knee OA associated with series of inflammatory cytokines typically seen in RA.
Deterioration of the medial or lateral meniscus – structures within the knee that help maintain proper alignment during joint motion – is often an early feature of osteoarthritis (OA). In the present study, patients with degenerative meniscal tears and minimal cartilage thinning were studied as a model for early OA. These patients were found to produce a series of inflammatory cytokines in their joints as has been shown for patients with rheumatoid arthritis (RA) and to a lesser extent advanced OA. The key observation is that one cytokine known as IL-15 was more likely to be elevated in knee joints of patients with early OA as compared to patients with advanced OA. This study defines a new approach to the study of OA at a time when the disease is relatively early in its course – a time when OA is most likely to be treatable with medical interventions.

So what? The important finding that early OA is associated with elevated IL-15 suggests that processes that drive production of IL-15 are active in early OA. Medications that block inflammation, especially if they reduce expression of IL-15, may slow or stop progression of OA if applied early in the course of the disease.

8. Autoimmune response to citrulline an important driver of the inflammation that damages joints in patients with RA.
Proteins are made up of amino acids, one of which is arginine. Under certain circumstances arginine is converted to an alternative amino acid know as citrulline. This conversion process occurs in joints of patients with rheumatoid arthritis (RA) who frequently develop anti-citrulline autoantibodies. Measurement of these antibodies has become an important clinical tool for diagnosing RA. The present study demonstrates that inducing anti-citrulline antibodies causes joint inflammation in a special strain of mice engineered to have genetic risk factors comparable to those associated with RA in humans. The results of this study indicate that the autoimmune response to citrulline is an important driver of the inflammation that damages joints in patients with RA.

So what? This study is an important step toward finding new treatments for RA that focus on controlling specific harmful autoimmune responses in RA. This approach promises to be more effective, safer and longer lasting than presently available medications for RA.

9. Medical decision making in patients with knee pain, meniscal tear, and osteoarthritis.
An estimated 27 million Americans have osteoarthritis (OA), and this number is on the rise. Up to 80 percent of individuals with knee OA will have meniscal tears detectable in MRI studies.

This problem is often treated surgically with an arthroscopic partial meniscectomy (APM) in which the surgeon uses an arthroscope to remove a damaged or loose portion of the damaged meniscus. The problem, however, is that we do not know which patients will benefit from this surgery and which will not. This study sought to answer the question by using a mathematical model based on published data regarding mechanical symptoms (such as locking and giving way), pain patterns, the type of meniscal injury as established by MRI, and the presence of bone marrow lesions to estimate who will benefit from the surgical procedure. In this analysis, individuals with a displaced tear, locking, increased pain, and no bone marrow lesions were judged to be the most likely to benefit from the procedure.

So what? Knowing which patients will benefit from APM is crucial for addressing a staggering public health dilemma. While a large scale clinical trial is needed to address this question definitively, the present study can help guide decision making when patients are considering the option of APM intervention.

10. Early intervention and treatment pathway
While it is known that long-term control or remission of RA may be possible with very early treatment, no optimal first therapeutic strategy has been determined. This study assessed the potential cost-effectiveness of three major therapeutic strategies for very early RA:

• A“pyramid” strategy with initial nonsteroidal anti-inflammatory drugs, patient education, pain management, low-dose glucocorticoids and DMARDs at one year for nonresponders
• Early DMARD therapy with methotrexate
• Early therapy with biologics and methotrexate

By reducing the progression of joint erosions and subsequent functional disability, both early intervention strategies increase quality-adjusted life more than the “pyramid” strategy and save long-term costs.

So what? This study establishes that very early intervention with disease-modifying antirheumatic drugs (DMARDs) is very cost-effective in terms of improving the quality of life for people with RA and provides a strong case for both physicians and insurers that early intervention in RA is essential. Further studies are needed to define the optimal time to begin treatment with newer biologic medications due to their substantial incremental cost.

Adapted from the Arthritis Foundation www.arthritis.org

Yes, it’s true…. And it’s not just people with arthritis. Research shows that people who can understand basic health information whether they receive it in writing, in person or over the phone can communicate with health professionals better, adhere and follow treatment and manage their condition better.

Being health literate means that you are clearly and accurately informed about your health. It involves you taking part in the decision making process and understanding your options when you fill out a consent form, go around a hospital or follow your doctors advice.

Recognising the significance of health literacy in Ireland, we’re glad to see that Ireland is to engage as a partner in the first EU health literacy survery. The EU survey will be carried out across eight European countries in September and provide the first real insight into the effect health literacy is having on society.

Ireland’s participation in the survey was funded partly by the European Agency for Health and Consumers and partly by The Department of Health and Children (through National Lottery funding) and UCD. The EU Health Literacy Survey findings will be published in February 2011 by Maastricht University, the University hosting the survey project… so watch this space for more.

If you’re living with arthritis and would like some support and information on understanding some of the terms and medical language used, contact the Arthritis Ireland helpline on LoCall 1890 252 846or email helpline@arthritisireland.ie to speak to our trained volunteers and to request a free copy of ‘Arthritis: Key words in plain language‘. Or, if you prefer you can visit the arthritis information section of our website here for this and any other booklet.

“The big one is that people who did not own dogs had over three times the odds of being treated for diabetes than those who walked their dogs,” says study author Cindy Lentino, an exercise scientist at George Washington University School of Public Health and Health Services in Washington, D.C.

For her study, Lentino looked at the general health of 916 middle-aged adults who fell into three categories – non-dog owners, those who own dogs and regularly walk them and those who have dogs but don’t walk them. She found that regular dog walkers had a lower body mass index and fewer chronic conditions and depressive symptoms than their counterparts. They also sat less every day, used less tobacco and had more social support.

The study was presented at the Annual Meeting of the American College of Sports Medicine, in Baltimore.

Lentino says her results indicate dog walking is something medical and health professionals should include when talking about activities that promote a healthy and active lifestyle.

“There’s definitely something special about dogs. They are inherently active animals,” Lentino says. “Dogs give owners a sense of purpose in that they need to be walked and humans need exercise, so I think that is the key. “

Other experts agree.

“I think it makes sense because you are doing more activity. You will be healthier and leaner,” says Bashir Zikria MD, assistant professor in the Department of Orthopaedics at Johns Hopkins Medical Institution in Baltimore. “You are getting upper body work by holding the dog and a lower body workout by walking, and best of all you get social interaction. “

Dr. Zikria says dog walking also solves one of the most difficult parts of an exercise plan – starting it.

“The hardest thing about working out is often getting that set schedule. You can easily say I’m not doing it today,” Dr. Zikria says. “But when you have a dog, you know you have to walk them. It gives you a set schedule. You can’t give excuses because you can’t let the dog down. It’s an obligation.”

So, why not bring your dog along to Pick a Peak for Arthritis Ireland on 24th July. It’s a great reason to get out and about with a man’s (or woman’s) best friend.

A new study has concluded that routine vaccinations given during adulthood are unlikely to increase the risk of developing rheumatoid arthritis.

Swedish scientists studied 2,000 people with rheumatoid arthritis, aged 18 to 70, as well as a further 2,000 healthy volunteers.

They looked at participants’ recent vaccination histories to see whether those who had received routine injections for flu, tetanus, diphtheria, tick-borne encephalitis, hepatitis A, B and C, polio and pneumococcus were more likely to develop the autoimmune disease.

Among the participants, 31 per cent had been vaccinated during the five-year study period.

Writing in the Annals of the Rheumatic Diseases, the researchers revealed that there were no differences in vaccination rates between the two groups of participants.

They also noted that vaccination did not increase the risk of rheumatoid arthritis in participants who smoked – a major risk factor for the disease – or in people with a particular genetic factor associated with the disease, called the HLA-DRB1 shared epitope allele.

The findings indicate that, despite fears that routine vaccinations might cause the body’s immune system to turn on itself and trigger long-term inflammatory conditions such as rheumatoid arthritis, that does not appear to be the case.

“It is unlikely that vaccinations in general should be considered a major risk factor for rheumatoid arthritis,” the study authors concluded.

“This has practical implications for what advice on vaccinations should be given to the general population and, in particular, to groups at risk of rheumatoid arthritis, such as children of patients with rheumatoid arthritis.”

However, the researchers conceded: “This result does not rule out the possibility that vaccinations given earlier in life, or vaccinations that are rare, may trigger the development of rheumatoid arthritis.”

A fifty-year study on osteoarthritis in moose suggests that many cases are linked to malnutrition at an early age – and that the same may well be true for humans.

Arthritis is often regarded as condition that affects some people as they age, but a growing body of evidence indicates that the roots are found early on in life.

Scientists at Michigan Technological University have been studying the problem in moose on a wilderness island national park in Lake Superior for five decades.

Since 1985, researchers have studied the skeletal remains of over 4,000 moose on Isle Royale.

Lead author Rolf Peterson, whose team’s findings are published in the journal Ecology Letters, revealed that moose osteoarthritis is “identical” to that found in humans and became increasingly apparent as the researchers entered the second decade of their study.

The team noticed that osteoarthritis became more common as the moose population increased and became less common when food was scarcer and the population shrank.

They also discovered that malnourished youngsters were more likely to develop osteoarthritis in older age.

Dr Peterson said that the study had provided a “unique insight” into the complex causes of osteoarthritis.

“We have shown how malnutrition early in life increased the risk of osteoarthritis later in life, but this also applies to humans as much as to a herd of moose in the wild,” he explained.

“The link between early nutrition and arthritis, in both people and moose, reveal that osteoarthritis is more complex than commonly assumed and involves connections between physiology, life histories, populations and communities, while highlighting the importance of the disorder for past and present humans.”

People with low back pain should stay active rather than remaining in bed, a new review has concluded.

The majority of doctors now advise patients to keep as active as possible and the latest review in the Cochrane Library supports that advice.

Researchers directly compared the effects of resting in bed and staying active by combining two previous Cochrane reviews from 2002 and 2004.

Patients suffering from low back pain without sciatica tended to experience improvements in pain intensity, regardless of whether they took bed rest or continued normal activity.

When patients who had been hospitalised for back pain during combat training were removed from the analysis, the researchers found that the remaining active patients experienced more significant reductions in pain and greater improvements in function than those who stayed in bed.

The researchers also looked at data on 348 patients whose back pain was accompanied by sciatica and found no difference in pain intensity or ability to function between those who kept active and those who stayed in bed.

“The available evidence neither supports nor refutes that advice to stay active is better than resting in bed for people with sciatica,” said Dr Kristin Thuve Dahm, who led the review at the Norwegian Centre for the Health Services.

“However, considering that bed rest is associated with potential harmful side-effects, we think it is reasonable to advise people with sciatica to stay active.”

Dr Dahm concluded: “Normal daily activity seems to be the best way for patients with low-back pain to get better.”

The researchers also noted that no clinical trials had looked at the relative effects of bed rest and normal activity on low back pain in recent years.

According to Dr Joel Press, professor in physical medicine and rehabilitation at the Feinberg Northwestern School of Medicine in Chicago, this shows that previous research had “already proved the point”.

He added: “Everyone is fairly convinced there’s not much benefit to bed rest. We’re almost always better moving than not moving.”

Surgical treatment for ligament and cartilage injuries in the knee does not reduce an individual’s risk of developing osteoarthritis, new research in the journal Radiology has found.

Scientists at Leiden University Medical Centre in The Netherlands followed-up 326 patients who had experienced knee pain before undergoing an MRI scan and treatment for a torn anterior cruciate ligament (ACL) or meniscal cartilage injury.

The ACL is one of four ligaments that connect the bones in the knee, while the meniscus is a wedge-shaped piece of cartilage that acts as a shock-absorber.

Researchers found that patients with ACL and meniscus tears faced a higher-than-average risk of osteoarthritis.

Ten years after their initial injury, patients typically showed signs of osteoarthritis in the affected area, regardless of whether or not they had undergone surgical repair.

The findings suggest that patients’ elevated risk of osteoarthritis was not reduced by surgery to repair the torn ligament or remove the damaged cartilage.

Lead author Dr Kasper Huetink, resident radiologist at Leiden University Medical Centre, commented: “This study proves that meniscal and cruciate ligament lesions increase the risk of developing specific types of knee osteoarthritis. Surgical therapy does not decrease that risk.

“We showed a direct relationship between injury and long-term consequences, and showed that surgery has no impact on long-term outcomes.”

Dr Huetink added that more research is needed to determine the short and long-term benefits of different types of surgical approach for a damaged meniscus.

First presentation of TENDER study demonstrates RoACTEMRA’s strong efficacy in this severe childhood condition with no currently licensed treatment

Roche announced that new data being presented at the European League Against Rheumatism (EULAR) congress demonstrates that RoACTEMRA (known as ACTEMRA outside Europe) is highly effective in improving the signs and symptoms of systemic Juvenile Idiopathic Arthritis (sJIA), a severe childhood arthritis, where there are no currently licensed treatments. RoACTEMRA is also well tolerated in children with sJIA having a safety profile similar to adults with RA.

Data from the phase III TENDER studyi showed that, following three months’ treatment with RoACTEMRA, 85 percent of patients achieved 30 percent improvement (JIA ACR30*) in the signs and symptoms of sJIA and absence of fever, a primary characteristic of sJIA, compared to 24 percent of patients receiving placebo. Further data showed 70 percent achieved JIA ACR70 and 37 percent achieved ACR90. In addition to the significant improvement in JIA ACR response nearly two thirds were free of rash after three months.

“There is a critical need for new therapies for children suffering from the debilitating and life-threatening effects of sJIA, and these data represent an exciting breakthrough”, commented Hal Barron, M.D, Head of Global Development and Chief Medical Officer for Roche. “RoACTEMRA’s striking efficacy confirms a major advance in the treatment of this disease. It promises to have a significant impact in the life of these young children.”

sJIA is characterised by chronic arthritis accompanied by intermittent fever, skin rash, anaemia, enlargement of the liver and/or spleen and inflammation of the lining of the heart and/or lungs.ii The peak age of onset of sJIA is between 18 months and two yearsiii,iv although persistence of the disease into adulthood does occur.

Its disease course is variable and in the most severe cases, up to two thirds of patients have chronic and persistent arthritis and approximately half of these will develop significant disabilityv,vi It has the worst long term prognosis of all childhood arthritis subtypes, accounting for almost two-thirds of all deaths among children with arthritis, with an overall mortality rate estimated to be between two to four percent.vii There are no approved therapies for sJIA and current treatment consists of high dose corticosteroids to control systemic symptoms. However, these do not improve the long-term prognosis and their use is accompanied by severe side effects.ii

The TENDER study findings reflect previous Japanese studiesviii,ix which demonstrated that RoACTEMRA is well tolerated and effective in children with sJIA who could not tolerate, or showed inadequate response to systemic corticosteroids and immunosuppressants. No new major safety signals were observed and the adverse event profile was similar to adult RA studies and as expected for this patient population.

RoACTEMRA inhibits the activity of interleukin-6 (IL-6), a contributor to the major features of sJIA including chronic synovial inflammation, articular cartilage damage, fever, anaemia, growth impairment and osteoporosis.x Commenting on IL-6 as a treatment approach, Hal Barron said: “RoACTEMRA’s efficacy in treating these symptoms provides further evidence of the pivotal role of IL-6 in mediating joint inflammation and the detrimental systemic effects of chronic inflammatory diseases.”

RoACTEMRA is already approved in the EU, US and other countries for adult RA, a disease also associated with elevated levels of IL-6 and systemic symptoms such as fatigue, anaemia and fever. Studies in RA have demonstrated RoACTEMRA’s strong efficacy and safety, with consistently high remission rates across all patient types and inhibition of structural joint damage.xii In addition it is the only product to have proven superiority to methotrexate in monotherapy in ACR20, ACR50 and ACR70 responses at six months, in adult RA.xiii