Patients With Rheumatoid Arthritis Challenged By Complications After Joint Replacement Surgery

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Article Date: 30 Nov 2012 – 0:00 PST

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In the first systemic review of evidence assessing complications following total joint arthroplasty, patients with rheumatoid arthritis (RA) were found to have an increased risk for hip dislocation after hip replacement surgery compared to those with osteoarthritis (OA). Study findings published online in Arthritis & Rheumatism, a journal of the American College of Rheumatology (ACR), also indicate that RA patients have a higher infection risk following total knee replacement than patients with OA.
The ACR reports that OA – the most common form of arthritis – affects 27 million Americans 25 years of age and older, and another 1.3 million adults are living with RA. Previous studies show that one of the most effective treatment options for end-stage arthritis of the hip or knee is total joint replacement. Experts suggest that success with this intervention is evident given the increasing rates of joint replacements. According to the Centers for Disease Control and Prevention (CDC) 676,000 total knee replacements and 327,000 total hip replacements were performed in the U.S. in 2009.
“Joint arthroplasty is successful in relieving the pain and disability caused by hip or knee arthritis,” said lead author Dr. Bheeshma Ravi from the University of Toronto and Women’s College Research Institute (WCRI) in Canada. “While complication rates are low there are some cases with serious consequences that include infection, joint dislocation, blood clots and even death.”
To explore this important issue, Dr. Ravi and colleagues conducted a systemic review of the literature to assess complication risk in OA and RA patients following joint replacement surgery. Evidence from January 1990 to December 2011 was evaluated and 40 studies were included in the analysis. The study population included patients aged 18 years or older who had hip or knee replacements and excluded patients who had replacement surgery due to a fracture or cancer. Studies that involved 200 joints or more were incorporated in the current analysis.
Analysis shows RA patients had a higher risk of dislocation following hip replacement surgery than patients with OA. RA patients who had total knee replacements were also at higher risk of infection compared to those with OA. The team found no difference in revision rate, 90-day mortality or blood clot risk between the two patient groups. Dr. Ravi concludes, “Additional studies to confirm our findings are necessary and further investigation of possible reasons for differences in joint replacement complication rates between RA and OA patients is needed.”


Full citation: “A Systematic Review and Meta-analysis Comparing Complications following Total Joint Arthroplasty for Rheumatoid Arthritis versus Osteoarthritis.” Bheeshma Ravi, Benjamin Escott, Prakesh S Shah, Richard Jenkinson, Jas Chahal, Earl Bogoch, Hans Kreder, Gillian Hawker. Arthritis & Rheumatism; Published Online: November 28, 2012 (DOI: 10.1002/art.37690).

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n.p. (2012, November 30). “Patients With Rheumatoid Arthritis Challenged By Complications After Joint Replacement Surgery.” . Retrieved fromhttp://www.medicalnewstoday.com/releases/253320.php.

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Hope For Arthritis Patients ‘Walking On Marbles’

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Article Date: 29 Nov 2012 – 1:00 PST

Hope For Arthritis Patients ‘Walking On Marbles’

Researchers at the University of Southampton are to undertake a new stage of a study aimed at improving the health and mobility of those suffering from the common complaint of ‘walking on marbles’ associated with Rheumatoid Arthritis (RA) in the feet.

RA is the second most common form of arthritis in the UK, affecting almost 600,000 people, which results in the destruction of joints around the body caused by inflammation.

Forefeet often contain some of the first joints to be affected and those with the condition often say that they feel like they are ‘walking on marbles’. Mostly, people have thought that this was due to walking on foot joints that are affected by the RA.

The Health Sciences’ FeeTURA study however, developed new ways of assessing the forefeet through the use of diagnostic ultrasound and magnetic resonance imaging techniques. From this work, the team discovered that some of the swellings and associated feeling of ‘walking on marbles’ were related to inflamed bursae (a fluid-filled sac usually found in areas subject to friction) that had developed underneath the forefoot joints. These inflamed bursae were rarely detected by clinical examination.

The exact cause of the inflamed bursae is not known and a cure is yet to be found, however, the team is now looking at identifying inflammatory and mechanical markers to find the best ways of treating this complication in people suffering with RA. They will evaluate foot health treatments, such as targeted steroid injections, as well as medical management through the use of new drugs (called biologics).

This new stage of the study will be funded through a partnership between Solent NHS Trust and the Faculty of Health Sciences at the University of Southampton and supported by a National Institute for Health Research (NIHR) clinical academic fellowship.

During the first stage of the study, which took place between 2006 and 2009, researchers at the University of Southampton developed a technique to better evaluate the forefeet and diagnose the ‘marbles’ using diagnostic ultrasound. Participants’ who were assessed at the NIHR Wellcome Trust Clinical Research Facility (WTCRF), based at Southampton General Hospital, returned for re-assessment in the second stage of the study which discovered the changes that had occurred in the condition.

A third stage used an MRI scan to visualise the anatomical structures and ‘marbles’ more clearly in the forefeet and resulted in researchers developing the first ever atlas to categorise the swellings originally identified in stage one.

Led by senior lecturer for Advanced Clinical and Expert Practice, Dr Catherine Bowen, this new stage of the treatment study will be carried out by clinical academic researcher, Lindsey Hooper, who recently won a prestigious special award from Wessex HIEC for the previously completed MRI work.

Dr Bowen comments: “Although more common in the UK than leukaemia and multiple sclerosis, awareness of the severity of rheumatoid arthritis is limited.

“Our linked study aims to significantly improve the lives of those affected by the condition in their forefeet, reducing the severity of the symptoms including pain, inflammation, poor sleep, fatigue and depression, and therefore helping improve their mobility and wellbeing.”

Lindsey Hooper adds: “This is an amazing opportunity to be involved in a study that is potentially life-changing for the many people suffering from this progressively debilitating condition.

“As I am maintaining my clinical role as a rheumatology podiatrist whilst also completing the research it means the findings can be fed directly back into clinical practice, so that local patients receive the most up-to-date care options.”

Article adapted by Medical News Today from original press release. Click ‘references’ tab above for source.
Visit our section for the latest news on this subject.
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n.p. (2012, November 29). “Hope For Arthritis Patients ‘Walking On Marbles’.” . Retrieved fromhttp://www.medicalnewstoday.com/releases/253302.php.

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Three Times More Women Than Men Suffer From Arthritis: Study Reveals Insights Into This Gender Bias

Main Category: Arthritis / Rheumatology
Also Included In: Genetics;  Women’s Health / Gynecology
Article Date: 19 Nov 2012 – 0:00 PST

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Three Times More Women Than Men Suffer From Arthritis: Study Reveals Insights Into This Gender Bias

Researchers have pieced together new genetic clues to the arthritis puzzle in a study that brings potential treatments closer to reality and could also provide insights into why more women than men succumb to the disabling condition.
Rheumatoid arthritis – which affects more than 400,000 people in the UK and about 1% of the world’s population – is a complicated disease: lifestyle and environmental factors, such as smoking, diet, pregnancy and infection are thought to play a role, but it is also known that a person’s genetic makeup influences their susceptibility to the condition.
Scientists at the Arthritis Research UK Epidemiology Unit at The University of Manchester have discovered 14 new genes that can lead to rheumatoid arthritis, adding to the 32 other genes they had already identified; the team believes it has now discovered the vast majority of disease-causing genes for the condition.
The Manchester researchers’ latest study, published in the journal Nature Genetics, has identified genes specific to the female X-chromosome – which could explain why three times more women than men present with the disease.
First author Dr Stephen Eyre said: “This work will have a great impact on the clinical treatment of arthritis; we have already found three genes that are targets for drugs, leaving a further 43 genes with the potential for drug development, helping the third of patients who fail to respond well to current medications.
“Although patients who first present at clinic have similar symptoms, it is likely that their route to developing disease has involved a varied path. The genetic findings can help divide patients into smaller groups with more similar types of rheumatoid arthritis and assist in the allocation of therapies and disease management.”
The Manchester team used advanced technology and a large collection of international samples to identify the new genes and move a step closer to being able to improve the lives of rheumatoid arthritis sufferers.
Professor Jane Worthington, study lead based at the NIHR Manchester Musculoskeletal Biomedical Research Unit, said: “This groundbreaking study brought together scientists from around the world and involved the use of DNA samples from more than 27,000 patients with rheumatoid arthritis and healthy controls. As a result of our findings, we now know that genetic variations at over 45 regions of the genome determine susceptibility to this form of arthritis.
“We observed remarkable similarities with genetic markers associated with other autoimmune diseases. Our future work will focus on understanding how the simple genetic changes alter normal biological processes and lead to disease. Ultimately, this will help us to develop novel therapies and improved targeting of existing drugs.”

Professor Alan Silman, medical director of Arthritis Research UK, said: “This large genetics study has added a significant amount to the current knowledge of the genetic basis of rheumatoid arthritis. We hope that this research will lead to a greater understanding of the disease and allow us to develop targeted drug treatments for the half-a-million people currently living with rheumatoid arthritis.

“This is the first time that a genetic association has been established between rheumatoid arthritis and the X chromosome. This could provide a useful clue in helping us to understand why rheumatoid arthritis is three times more likely to occur in women.”

Article adapted by Medical News Today from original press release. Click ‘references’ tab above for source.
Visit our arthritis / rheumatology section for the latest news on this subject.
The paper: ‘High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis’ is published in Nature GeneticsUniversity of Manchester
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n.p. (2012, November 19). “Three Times More Women Than Men Suffer From Arthritis: Study Reveals Insights Into This Gender Bias.” . Retrieved fromhttp://www.medicalnewstoday.com/releases/252896.php.

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Anti-Flammatory Benefits Likely To Be Revealed In Rare Parasitic Fungi

Main Category: Immune System / Vaccines
Also Included In: Respiratory / Asthma;  Arthritis / Rheumatology
Article Date: 17 Nov 2012 – 0:00 PST

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Caterpillar fungi (Cordyceps) are rare parasites found on hibernating caterpillars in the mountains of Tibet. For centuries they have been highly prized as a traditional Chinese medicine – just a small amount can fetch hundreds of pounds.
Scientists at The University of Nottingham have been studying how this fungus could work by studying cordycepin, one of the drugs found in these mushrooms. They have already discovered that cordycepin has potential as a cancer drug. Their new work indicates that it could also have anti-inflammatory characteristics with the potential to help sufferers of asthma, rheumatoid arthritis, renal failure and stroke damage.
The research, published in the academic journal RNA, was led by Dr Cornelia de Moor in the School of Pharmacy. It shows that cordycepin reduces inflammatory gene products in airway smooth muscle cells – the cells that contract during an asthma attack.
Several studies have suggested that cordycepin could be an effective drug for a variety of conditions, including cancer, stroke, kidney damage and inflammatory lung disease but until now it was unclear how cordycepin could bring about so many different beneficial effects at the cellular level.
Dr de Moor said: “We have shown that cordycepin reduces the expression of inflammatory genes in airway smooth muscle cells by acting on the final step in the synthesis of their messenger RNAs (mRNAs) which carry the chemical blueprint for the synthesis of proteins. This process is called polyadenylation. Commonly used anti-inflammatory drugs either work much earlier in the activation of inflammatory genes, such as prednisone, or work on one of the final products of the inflammatory reaction (e.g. ibuprofen).These findings indicate that cordycepin acts by a completely different mechanism than currently used anti-inflammatory drugs, making it a potential drug for patients in which these drugs don’t work well.
“However, it is a surprise that cordycepin does not affect the synthesis of mRNAs from other genes, because nearly all mRNAs require polyadenylation.”
Dr de Moor’s research suggests that this is because inflammatory genes can be very rapidly induced and that cordycepin has its many and varied effects by altering the synthesis of other classes of rapidly induced genes as well. If this is true if could be said that cordycepin slows down the rapid cellular responses to tissue damage and may work by preventing the over-activation of these responses which are associated with conditions such as asthma, rheumatoid arthritis, renal failure, cancer and stroke damage.
However, it also indicates that cordycepin could have adverse effects on normal wound healing and on the natural defences against infectious diseases.
Dr de Moor said: “We are hoping to further investigate which genes are more dependent on polyadenylation than others and why this is the case, as well as test the effect of cordycepin on animal models of disease. Clinical testing of cordycepin is not in our immediate plans, as we think we first have to understand this drug in more detail before we can risk treating patients with it.”

Article adapted by Medical News Today from original press release. Click ‘references’ tab above for source.
Visit our immune system / vaccines section for the latest news on this subject.
Additional funding has been awarded by the Biotechnology and Biological Sciences Research Council to continue this vital work.
University of Nottingham
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Aging Overweight Males At Increased Risk For Gout, Rheumatoid Arthritis

Main Category: Gout
Also Included In: Arthritis / Rheumatology;  Men’s Health;  Seniors / Aging
Article Date: 13 Nov 2012 – 0:00 PST

Aging Overweight Males At Increased Risk For Gout, Rheumatoid Arthritis

Refuting a belief long held by many physicians, a Mayo Clinic study found that rheumatoid arthritis patients also can get gout. The research is among several studies Mayo Clinic presented at the American College of Rheumatology annual meeting in Washington. Researchers also found that gut bacteria has potential to treat autoimmune disorders, rheumatoid arthritis patients are at higher risk for cancer, broken bones put rheumatoid arthritis patients in greater danger of heart disease and death, and corticosteroids are a mainstay of rheumatoid arthritis treatment even as new drugs emerge.
The gout study shows that, contrary to conventional wisdom, rheumatoid arthritis patients aren’t immune to the nation’s obesity-fueled gout epidemic, says lead author Eric Matteson, M.D., chair of the Division of Rheumatology at Mayo Clinic in Rochester, Minn. The two are distinct conditions, treated differently. Rheumatoid arthritis is an autoimmune disease in which the immune system mistakenly attacks tissues, inflaming joints. In gout, the body produces too much uric acid or has problems flushing it out, and urate crystals build up in joints, causing inflammation and intense pain.
The reason it was thought that rheumatoid arthritis patients didn’t get gout likely had to do with the way rheumatoid arthritis used to be treated, Dr. Matteson says. Such patients used to be given aspirin in high doses, and that coincidentally helped their kidneys expel uric acid. Aspirin is no longer used much for rheumatoid arthritis, and that, combined with a rise in obesity, is likely fueling gout in rheumatoid arthritis patients, he says.
“It is probably true that flares of rheumatoid arthritis in some cases might have actually been flares of gout, and that the gout wasn’t diagnosed; it wasn’t realized that it was a coexistent problem,” Dr. Matteson says. “Awareness that gout does exist in patients with rheumatoid arthritis hopefully will lead to better management of gout in those patients.”
Researchers studied 813 patients diagnosed with rheumatoid arthritis between 1980 and 2007 and followed them as long as they were alive and in the county, until last April. The study used the Rochester Epidemiology Project, a National Institutes of Health-supported pool of Olmsted County, Minn., patient medical records from Mayo and other health care providers.
Twenty-two patients developed gout over the study period, most often in the big toe. Gout was more common in patients diagnosed with rheumatoid arthritis from 1995 on. The risk factors for gout were the same as in the general population: being overweight, being older and being male.

Other Mayo studies being presented at the rheumatology conference found that:

  • Gut bacteria, specifically Prevotella histicola, have anti-inflammatory benefits that could help treat autoimmune disorders such as lupus, rheumatoid arthritis and ankylosing spondylitis. Researchers examined the possibility using mice, and more studies are planned. “This is a hot area of research now,” says Dr. Matteson, who wasn’t part of the study team.
  • Corticosteroids, whose discovery at Mayo Clinic earned the Nobel Prize in 1950, are still a common treatment for rheumatoid arthritis even as newer drugs with fewer side effects emerge. The proportion of patients on the drugs at any given point in their rheumatoid arthritis is actually higher than it used to be, the study found. “Not only do we think that they’re helpful in controlling symptoms of disease, especially in the first year, but we also are realizing that they have some effect in modifying the disease course,” says Dr. Matteson, the lead author. “We try to use the minimum amount possible for the shortest time necessary.”
  • Rheumatoid arthritis patients have a higher risk of developing blood cancers, particularly lymphoma. One of the immune system’s top jobs is to seek and destroy cancer cells, and in rheumatoid arthritis patients that can fail due to the autoimmune disorder itself and to drugs that treat it by suppressing the immune system, Dr. Matteson, the lead author, says. More research is needed to understand the risk factors in individual patients. A small number of patients get lymphoma, and they tend to have more severe rheumatoid arthritis, Dr. Matteson says.
  • Rheumatoid arthritis patients who have cardiovascular disease are more likely to test positive for rheumatoid factor in their blood, and those who are positive for rheumatoid factor seem to have immune systems that age faster and also have accelerated risk of cardiovascular disease.
  • Rheumatoid arthritis patients who have broken bones are at higher risk of cardiovascular disease and death. The chronic inflammation in rheumatoid arthritis may be a factor.

Article adapted by Medical News Today from original press release. Click ‘references’ tab above for source.
Visit our gout section for the latest news on this subject.
The following abstracts included conflict-of-interest disclosures:
rheumatoid arthritis and gout; mortality after fragility fractures; accelerated aging; and fractures associated with increased risk of cardiovascular events. For more information, see the ACR abstract supplement.
Mayo Clinic
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The word gout comes from Latin gutta and old French gote meaning “a drop”. Several hundred years ago gout was thought to be caused by drops of viscous humors that seeped from blood into the joints. Read more…

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The Impact Of Rheumatoid Arthritis And Lupus On Joint Replacement Surgery Outcomes

Main Category: Arthritis / Rheumatology
Also Included In: Lupus;  Bones / Orthopedics
Article Date: 13 Nov 2012 – 0:00 PST

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Two new studies by researchers at Hospital for Special Surgery have overturned common beliefs about joint replacement in patients with lupus and rheumatoid arthritis (RA).
In one study, researchers demonstrated that RA patients who undergo a knee replacement can expect outcomes that are similar to individuals undergoing the operation for osteoarthritis. In the other, investigators showed that lupus patients undergoing joint replacement surgery experienced far fewer adverse events than previously thought. The news will be reported at the annual meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals, being held Nov. 9-14, in Washington D.C.
Both studies relied on analyses of data from the HSS Total Joint Replacement Registry. Started in 2007, this prospective registry includes, among other things, data on all patients who seek care at HSS for knee and hip replacement surgery.
Lupus
Patients with lupus frequently need joint replacement surgery because they are treated with steroids that can lead to osteonecrosis (bone death caused by poor blood supply). Because little information is available about how lupus patients fare after surgery today, HSS researchers used the HSS Total Joint Replacement Registry to identify 101 lupus patients who underwent knee replacement (45) or hip replacement (56). They then matched each case to two similar patients who underwent the operation for osteoarthritis.
Patient pain and function had been assessed prior to surgery and two years after surgery using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). WOMAC measures pain, stiffness, and functional limitation. It is one of the more widely used measuring tools for outcomes after total knee replacement. The investigators also used the Lower Extremity Activity Score (LEAS) to measure function. This score quantifies how much activity a person is capable of performing, ranging from being able to get out of bed to participate in vigorous physical activity.

The researchers found that two years after surgery, total hip replacement and total knee replacement pain and function outcomes were similar in patients with lupus compared with individuals who did not have lupus. Patients with lupus had much worse pain and function scores compared to their controls prior to surgery, but two years after the surgery, the scores were similar. Results from the short-form (SF)-36 health survey that measures general health demonstrated that patients with lupus scored significantly worse than other patients both before and after surgery.

In addition, the investigators found that almost none of the lupus patients who underwent knee replacement surgery did so because they had osteonecrosis, which was unexpected as traditionally osteonecrosis is thought to be high in lupus patients. Lupus patients who underwent hip replacement did have osteonecrosis, were younger (average age 54), and had a lot of lupus-related illness, including kidney disease and high blood pressure. compared with lupus patients undergoing the knee procedure. Total knee replacement patients were also heavier. In other words, they had characteristics typically seen in regular middle-aged patients who undergo a knee replacement for osteoarthritis.

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“People have thought of these lupus patients as very ill and, yes, they are worse when they go into surgery and they are sicker when you look at their comorbidities, but actually they do almost as well as the OA patients,” said Lisa Mandl, M.D., M.P.H., a rheumatologist at Hospital for Special Surgery, in New York City, who was involved with the study.

“Before this study, our assumption was that lupus patients underwent arthroplasty for osteonecrosis at least half of the time and that they don’t do as well,” said Susan Goodman, M.D., a rheumatologist at HSS, who led the study. “We now know that they do very well in terms of pain and function outcomes and that the knee patients are very unlikely to have osteonecrosis. They resembled their age matched control peer group.”

Rheumatoid Arthritis

In a second study, researchers used the same registry to compare outcomes of rheumatoid arthritis (RA) patients who undergo knee replacement surgery to a control group of individuals undergoing the operation for osteoarthritis. Historically, RA patients have had higher rates of post-operative adverse events, but whether this was due to poorly controlled disease or the treatment of the disease was unclear. Starting in the 1980s, effective disease modifying drugs became available to treat patients with RA. In the late 1990s, entanercept, infliximab, and other biologic medication came on the market. Today, at HSS over 70% of patients are on immunomodulating drugs and over 50% are on biologics. Clearly these patients are very different from RA patients in past.

To investigate outcomes in these contemporary RA patients undergoing TKRs, investigators used the HSS Total Joint Replacement registry to identify 159 RA patients who underwent TKR and matched each case to two similar patients who underwent the operation for osteoarthritis. While patients with RA had worse pain and function and lower perceived health status prior to surgery compared to controls, there was no difference in operation time or in the time spent in the hospital post surgery. There were no deep joint infections in either group and no difference in superficial infections or rates of thromboembolism. Reoperations, mainly due to manipulation, were actually slightly higher in patients with osteoarthritis (8.8% vs. 2.5%).

“When a patient undergoes knee replacement, if they haven’t regained adequate motion, our surgeons will sometimes put them under a nerve block or general anesthesia and literally bend the knee to restore motion. This is called manipulation,” said Dr. Goodman who led the study.

The study shows that, contrary to common belief, infection and wound healing complication rates are not increased in patients with RA who undergo knee replacement, at least in a high volume hospital.

“Our concern was that in an era characterized by high level use of disease modifying drugs and immunosuppressants, the likelihood of infection would be greater,” Dr. Goodman said. “This study shows we are well-educated about the risk of these drugs and we seem to be managing them. At least at HSS, we are not seeing a lot of infections.”

“In this modern era, where RA patients come into surgery less sick, it looks like rheumatoid arthritis might not be the major risk factor that it once appeared to be in terms of short term adverse events,” Dr. Mandl said.

Article adapted by Medical News Today from original press release. Click ‘references’ tab above for source.
Visit our arthritis / rheumatology section for the latest news on this subject.

Both studies were supported by a Centers for Education and Research on Therapeutics grant from the Agency for Healthcare Research and Quality.

Other investigators involved in the rheumatoid arthritis study are Lisa Mandl, M.D., MPH, Mark Figgie, M.D., and Michael Alexiades, M.D., from HSS, and Zac LoVerde from New York Medical College. The study is being presented on Tuesday, November 13, at 2:30.

Other investigators involved in the lupus study are Lisa Mandl, M.D., MPH, and Mark Figgie, M.D., from HSS, and Ummara Shah, M.D., from New York University School of Medicine. The study is being presented on Tuesday, November 13, at 10:30 a.m.

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Xeljanz Approved For Rheumatoid Arthritis Treatment By FDA

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Main Category: Arthritis / Rheumatology
Also Included In: Bones / Orthopedics;  Regulatory Affairs / Drug Approvals
Article Date: 08 Nov 2012 – 0:00 PST

Xeljanz Approved For Rheumatoid Arthritis Treatment By FDA
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The U.S. Food and Drug Administration approved a drug by the name of Xeljanz (tofacitinib) for patients who have an insufficient or allergic response to methotrexate, as treatment for fiercely active rheumatoid arthritis.Rheumatoid arthritis (RA) is an autoimmune disease, in which the body’s healthy tissue is under attack by the immune system. This leads to inflammation of the joints and surrounding tissues. RA affects about 1.5 million Americans according to the Centers for Disease Control and Prevention.

Xeljanz is a pill taken twice a day that functions by inhibiting molecules known as “Janus kinases”, crucial to the joint inflammation that characterizes RA.

“Xeljanz provides a new treatment option for adults suffering from the debilitating disease of RA who have had a poor response to methotrexate,” said Badrul Chowdhury, M.D., Ph.D., director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research.

Xeljanz is approved before the product’s prescription drug user fee goal date of November 21, 2012.

The effectiveness and safety of Xeljanz were tested during seven clinical trails that included adult patients with moderate to severe RA. Trial participants were given Xeljanz or a placebo.
Those treated with Xeljanz exhibited improvement in physical mobility and clinical response compared with those who received the placebo.

A risk documented explains that with the use of Xeljanz, there is an elevated risk of serious infections, like opportunistic infections, tuberculosis, cancers, and lymphoma. It also carries a warning against increases in cholesterol, increases in liver enzyme tests, and reductions in blood counts.
Xeljanz was approved with a Risk Evaluation and Mitigation Strategy (REMS). This includes a Medication Guide specifying crucial directions and safety information for patients, in addition to content for healthcare providers about the side effects associated with the drug.

The FDA is now requiring a post-marketing study in order to examine the long-term outcomes of Xeljanz on heart disease, serious infections and cancer. They recommend a comparison with a group of patients on another approved treatment to view any differences.

During the clinical trials, investigators saw upper respiratory tract infections, diarrhea, inflammation of the nasal passage and upper part of the pharynx, and headaches as the most frequent side effects.

What is Rheumatoid Arthritis?

Rheumatoid arthritis, also known as rheumatoid disease, is an autoimmune disease which is characterized by chronic joint inflammation. It may also involve inflammation of the eyes, heart, lungs and other tissues.

Rheumatoid arthritis is known as a “systemic illness”, i.e. it can affect many parts of the body.
Although rheumatoid arthritis is a long-term (chronic) disease, patients may go through long spells with no symptoms at all.

With rheumatoid arthritis, the synovium (synovium) is attacked by the immune system, resulting in inflammation and pain. Untreated patients risk deformity.

The disease is considerably more common in females than males and usually strikes when the person is between 40 and 60 years old. However, people of all ages, including children can be affected.

Written by Kelly Fitzgerald
Copyright: Medical News TodayNot to be reproduced without permission of Medical News Today

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n.p. (2012, November 8). “Xeljanz Approved For Rheumatoid Arthritis Treatment By FDA.” . Retrieved fromhttp://www.medicalnewstoday.com/articles/252517.php.

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Scientists Discover A New Type Of Anti-Inflammatory Drug That Also Works Against Arthritis And Related Conditions

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Also Included In: Immune System / Vaccines
Article Date: 03 Nov 2012 – 0:00 PDT

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Scientists at The Scripps Research Institute (TSRI) have discovered the first selective inhibitors of an important set of enzymes. The new inhibitors, and chemical probes based on them, can now be used to study the functions of enzymes known as diacylglycerol lipases (DAGL), their products, and the pathways they regulate. Early tests in mouse macrophages suggest that DAGL-inhibiting compounds might also have therapeutic uses, for they suppress the production of a pro-inflammatory molecule that has been implicated in rheumatoid arthritis and related conditions.
“We’ve developed the first set of chemical probes that effectively allows one to study these DAGL enzymes in living cell and animal models,” said Benjamin F. Cravatt, chairman of the Department of Chemical Physiology, professor in the Dorris Neuroscience Center and member of the Skaggs Institute for Chemical Biology at TSRI. Cravatt and his laboratory conducted the new study, published in the current issue of the journal Nature Chemical Biology.
Important But Poorly Understood
DAGL enzymes have been of interest mainly because of their role in making 2-AG (2-Arachidonoylglycerol), an important cannabinoid that is naturally produced in humans and other mammals. Cannabinoids are named for Cannabis (marijuana) plants, because they stimulate the same cellular receptors that are hit by marijuana’s active ingredients. Drugs that can enhance 2-AG’s signaling in the nervous system are being developed as treatments for pain, depression and anxiety.
But 2-AG exists in various tissues throughout the body, and on the whole, its functions are not well understood. Until now researchers have lacked enzyme inhibitors that can usefully probe those functions by selectively shutting off 2-AG’s production. “Existing DAGL inhibitors block many other enzymes, are not very potent, and do a poor job of getting into cells,” Cravatt said. “There has been a need for better chemical tools in this area.”
Cravatt’s laboratory had previously developed a set of compounds that act as potent inhibitors of serine hydrolases – the broad enzyme family to which DAGL enzymes belong. In the new study, Cravatt’s team, including first author Ken Hsu, a Hewitt Foundation postdoctoral researcher in the Cravatt laboratory, screened a library of these compounds for specific activity as DAGL inhibitors.
A Big Improvement

After finding a promising lead compound, Hsu and his colleagues chemically optimized it to obtain KT109 and KT172. The former selectively inhibits DAGLβ, the main enzymatic producer of 2-AG outside the nervous system. KT172 inhibits both DAGLβ and DAGLα, which is principally responsible for making 2-AG within the nervous system.

In a big improvement over previously described DAGL inhibitors, KT109 and KT172 are highly selective (i.e., they do not block many other, non-DAGL enzymes) and active in cells and animals. By analyzing the structures of their initial DAGL inhibitors, the team was also able to devise a new DAGL-tailored activity-based probe that binds to the active site of DAGLs and fluorescently labels these low-abundance and difficult-to-detect enzymes in cell or tissue samples. “Without the DAGL-specific probe, we would have found it very difficult to develop, optimize and confirm target engagement for our DAGL inhibitors,” Hsu said.

In neuron-like mouse cells, human prostate cancer cells, and mouse liver cells and macrophages (a type of immune cell that is frequently involved in inflammatory conditions), the DAGL inhibitors were able to inactivate DAGLβ activity. “At the optimal doses used, we were able to achieve selective and near-complete inhibition of the enzyme,” said Hsu. In these cell and animal studies, the inhibitors also reduced levels of 2-AG as well as arachidonic acid, another bioactive lipid that DAGL enzymes can regulate.

New Questions

2-AG is known to have an anti-inflammatory effect when it activates cannabinoid receptors on macrophages. Thus, one might expect that knocking down 2-AG production with a DAGL inhibitor would have a pro-inflammatory effect. Instead, Hsu, Cravatt and their colleagues found that blocking DAGL in mouse macrophages that had been stimulated with pro-inflammatory agents markedly lowered their secretion of TNFα, a major inflammatory signaling molecule.

Blocking DAGL has potential effects on multiple lipid signaling pathways in cells, and the researchers aren’t yet certain which of these effects explains the surprising suppression of TNFα. “The effect is dependent on DAGLβ, though, because we see the same result in DAGLβ knockout mice,” said Hsu. Cravatt added that their observations of the unexpected DAGL-inhibition effects in mouse macrophages could be due to the suppression of pro-inflammatory eicosanoids that derive from downstream metabolites regulated by DAGLβ.

TNFα is a key instigator of the inflammation seen in rheumatoid arthritis, and antibodies directed against TNFα are now front-line therapies for the condition. “What we’ve done so far is just early-stage cell biology, but conceivably the further optimization of our DAGL inhibitors could result in a new type of anti-inflammatory drug that also works against arthritis and related conditions,” Cravatt said.

Cravatt and his team are now studying the pathways through which the new inhibitors have this anti-inflammatory effect. They also plan to develop new inhibitors that will selectively block DAGLα and 2-AG production in the central nervous system.

Article adapted by Medical News Today from original press release. Click ‘references’ tab above for source.
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The other co-authors of the study, “DAGLβ inhibition perturbs a lipid network involved in macrophage inflammatory responses,” were Katsunori Tsuboi, Alexander Adibekian, Holly Pugh and Kim Masuda, all of the Department of Chemical Physiology at TSRI.
The research was supported by grants from the National Institutes of Health (DA009789, DA033760, MH084512) and a Hewitt Foundation Postdoctoral Fellowship.
Scripps Research Institute
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Arthritis Patients’ Lives Improved By Complementary And Alternative Therapy

Main Category: Arthritis / Rheumatology
Also Included In: Complementary Medicine / Alternative Medicine
Article Date: 31 Oct 2012 – 3:00 PDT

Arthritis Patients’ Lives Improved By Complementary And Alternative Therapy
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Nearly a quarter of patients with rheumatoid arthritis and osteoarthritis used complementary and alternative therapy (CAT) to help manage their condition, according to a study in the November issue of the Journal of Clinical Nursing.
Researchers interviewed 250 patients aged between 20 and 90 years of age. More than two-thirds (67%) had rheumatoid arthritis and the remainder had osteoarthritis.
They found that 23% used CAT in addition to prescribed drugs and that just under two-thirds of those (64%) felt that the therapy was beneficial, reporting improvements in pain intensity, sleeping patterns and activity levels. “Our study underlines the importance of healthcare professionals being knowledgeable about the potential use of CAT when providing medical care to patients with arthritis” says lead author Professor Nada Alaaeddine, Head of the Regenerative and Inflammation Lab in the Faculty of Medicine, University of St Joseph, Beirut, Lebanon.
“Although CAT might have beneficial effects in rheumatoid arthritis and osteoarthritis, patients should be cautious about their use and should tell their healthcare providers that they are using them to make sure they don’t conflict with their existing treatment.”
Key findings of the survey included:

  • CAT users had an average age of 45 years, significantly younger than the average non CAT user, who was aged 57 years.
  • CAT use was higher in patients with osteoarthritis (29%) than rheumatoid arthritis (20%).
  • The most common CAT used was herbal therapy (83%), followed by exercise (22%), massage (12%), acupuncture (3%), yoga and meditation (3%) and dietary supplements (3%).
  • Just under a quarter of the patients using CAT (24%) sought medical care because of possible side effects, but they were not serious and were reversible. The most common side effects included skin problems (16%) and gastrointestinal problems (9%).
  • The majority did not tell their healthcare provider about their CAT use (59%).
  • CAT users were asked to rate the amount of pain they felt and the percentage who said that they experienced no pain rose from 12% to 43% after CAT use. The number who slept all night rose from 9% to 66%.
  • CAT users also reported an improvement in daily activities. The percentage who said that their pain did not limit them at all rose from 3% to 12% and the percentage who said they could do everything, but with pain, rose from 26% to 52%.

“CAT use is increasing and this study shows that it provided self-reported benefits for patient with rheumatoid arthritis and osteoarthritis” says Professor Alaaeddine.
“It is, however, important that patients discuss CAT use with their healthcare practitioner and that they are made aware of possible side effects, in particular the possible interactions between herbal and prescribed drugs.”

Article adapted by Medical News Today from original press release. Click ‘references’ tab above for source.
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“Use of complementary and alternative therapy among patients with rheumatoid arthritis and osteoarthritis.” Alaaeddine et al.Journal of Clinical Nursing. 21, pp3198-3204. (November 2012). doi: 10.1111/j.1365-2702.2012.04169.x
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ACR Supports Best Practices For Ultrasonography Use In Rheumatology

Main Category: Arthritis / Rheumatology
Also Included In: Lupus;  Gout
Article Date: 31 Oct 2012 – 0:00 PDT

ACR Supports Best Practices For Ultrasonography Use In Rheumatology
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More rheumatologists are embracing musculoskeletal ultrasound (MSUS) to diagnose and manage rheumatic diseases. In response, the American College of Rheumatology (ACR) assembled a task force to investigate and determine best practices for use of MSUS in rheumatology practice. The resulting scenario-based recommendations, which aim to help clinicians understand when it is reasonable to integrate MSUS into their rheumatology practices, now appear online in Arthritis Care & Research.
In Europe, more than 100 million individuals are affected by rheumatic diseases, according to the European League Against Rheumatism (EULAR). The ACR estimates that nearly 50 million Americans are burdened by arthritis and more than 7 million individuals suffer from inflammatory rheumatic diseases such as systemic lupus erythematosus, rheumatoid arthritis and gout.
“With so many people affected by rheumatic diseases, including arthritis, a diagnostic tool such as MSUS that is minimally invasive and with little risk to patients is an important tool for rheumatologists,” explains lead researcher Dr. Tim McAlindon from Tufts Medical Center in Boston, Mass. “Our task force goal was to establish when use of MSUS was ‘reasonable’ in a number of medical situations.”
The task force reviewed medical literature to come up with scenario-based recommendations for how MSUS could be used in rheumatology practice. These recommendations include a rating by type of evidence, with Level A supported by at least two randomized clinical trials or one or more meta-analyses of randomized trials; Level B backed by one randomized trial, non-randomized studies or meta-analyses of non-randomized studies; and Level C confirmed by consensus expert opinion, case studies, or standard clinical care.
The complete list of 14 recommendations of the reasonable use of MSUS in rheumatology, along with level of evidence, is published in the article. Partial list of recommendations includes:

  • For a patient with articular pain, swelling or mechanical symptoms, without definitive diagnosis on clinical exam, it is reasonable to use MSUS to further elucidate the diagnosis at the following joints: glenohumeral, acromioclavicular, sternoclavicular, elbow, wrist, metacarpophalangeal, interphalangeal, hip, knee, ankle, midfoot and metatarsophalangeal. Level of evidence: B.
  • For a patient with diagnosed inflammatory arthritis and new or ongoing symptoms without definitive diagnosis on clinical exam, it is reasonable to use MSUS to evaluate for inflammatory disease activity, structural damage or emergence of an alternate cause at the following sites: glenohumeral, acromioclavicular, elbow, wrist, metacarpophalangeal, interphalangeal, hip, knee, ankle, midfoot and metatarsophalangeal, and entheseal. Level B.
  • For a patient with shoulder pain or mechanical symptoms, without definitive diagnosis on clinical exam, it is reasonable to use MSUS to evaluate underlying structural disorders; but not for adhesive capsulitis or as preparation for surgical intervention. Level B.
  • It is reasonable to use MSUS to evaluate the parotid and submandibular glands in a patient being evaluated for Sjögren’s disease to determine whether they have typical changes as further evidence of the disorder. Level B.
  • For a patient with symptoms in the region of a joint whose evaluation is obfuscated by adipose or other local derangements of soft tissue, it is reasonable to use MSUS to facilitate clinical assessment at the glenohumeral, acromioclavicular, elbow, wrist, hand, metacarpophalangeal, interphalangeal, hip, knee, ankle/foot, and metatarsophalangeal joints. Level C.
  • For a patient with regional neuropathic pain without definitive diagnosis on clinical exam, it is reasonable to use MSUS to diagnose entrapment of the median nerve at the carpal tunnel; ulnar nerve at the cubital tunnel; and posterior tibial nerve at the tarsal tunnel. Level B.
  • It is reasonable to use MSUS to guide articular and peri-articular aspiration or injection at sites that include the synovial, tenosynovial, bursal, peritendinous and perientheseal areas. Level A.

The benefits of MSUS use include a faster, more accurate diagnosis, better measurement of treatment success, reduced procedural pain, and improved patient satisfaction. However, the authors highlight that economic impact was not part of this study. Dr. McAlindon concludes, “Further study of the cost-effectiveness and long-term outcomes of MSUS is necessary to determine its value compared to other interventions.”

Article adapted by Medical News Today from original press release. Click ‘references’ tab above for source.
Visit our arthritis / rheumatology section for the latest news on this subject.
Full citation: American College of Rheumatology Report on Reasonable Use of Musculoskeletal Ultrasonography in Rheumatology Clinical Practice.” Timothy McAlindon, Eugene Kissin, Levon Nazarian, Veena Ranganath, Shraddha Prakash, Mihaela Taylor, Raveendhara R Bannuru, Sachin Srinivasan, Maneesh Gogia, Maureen A McMahon, Jennifer Grossman, Suzanne Kafaja, John FitzGerald. Arthritis Care and Research; Published Online: October 29, 2012 (DOI: 10.1002/acr.21836).Wiley
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