Discovery Could Lead to Earlier RA Treatment

By Pat Anson, Editor

Scientists have discovered a new protein that regulates the severity of tissue damage caused by rheumatoid arthritis, a finding that could help identify RA patients earlier for more aggressive treatment.

The protein – known as C5orf30 – was found in DNA and biopsy samples from the joints of over 1,000 RA patients in the UK and Ireland.

"Our findings provide a genetic marker that could be used to identify those RA patients who require more aggressive treatments or personalized medicine," said Professor Gerry Wilson from the School of Medicine and Medical Science, University College Dublin, who led the research.

"They also point to the possibility that increasing the levels of C5orf30 in the joints might be a novel method of reducing tissue damage caused by RA".

Rheumatoid arthritis is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing joint pain, inflammation and bone erosion. About 1.5 million Americans and 1% of adults worldwide suffer from RA.

"These exciting findings will prompt us to further explore the role of this highly conserved protein that we know so little about, and its significance in human health and disease,” said co-author Dr. Munitta Muthana from the Medical School at the University of Sheffield.

The study, funded by Arthritis Ireland and the University of Sheffield, is published in the journal PNAS.

It is estimated that 30% of patients with rheumatoid arthritis are unable to work within 10 years of onset of the disease. It affects more women than men, and often more severely. RA is most common between the ages of 40 and 70, but it can affect people of all ages, including children.

Although there is no cure for RA, new drugs are available to treat the disease and slow joint damage. Self-management of the condition by patients, including exercise, is also known to reduce pain and disability.

One of the biggest problems in treating RA is early diagnosis and treatment, which can reduce the amount of joint damage.  

"Treatments for arthritis have improved enormously over the last number of years. Thirty years ago, rheumatologists' waiting rooms were filled with people in wheelchairs. Today, that is no longer the case. The outlook for a person diagnosed with arthritis in 2015 is much brighter than it used to be,” said John Church, CEO of Arthritis Ireland.

British researchers recently said they were close to developing a blood test that could detect both RA and osteoarthritis in its earliest stages.

Osteoarthritis (OA) is a progressive joint disorder caused by painful inflammation of soft tissue, which leads to thinning of cartilage and joint damage in the knees, hips, fingers and spine.

Researchers at the University of Warwick’s Medical School identified a biomarker linked to both forms of arthritis. Diagnostic blood tests already exist for RA, but the newly identified biomarker could lead to one which can diagnose both RA and osteoarthritis.

“This discovery raises the potential of a blood test that can help diagnose both RA and OA several years before the onset of physical symptoms," said lead researcher Naila Rabbani, PhD.

Rabbani’s research focused on citrullinated proteins (CPs), a biomarker present in the blood of people with early stage rheumatoid arthritis. Patients with RA have antibodies to CPs and the Warwick researchers established for the first time that CPs levels also increase in early-stage OA.

That research is published online in Nature Scientific Reports.

Quell Device Relieves Variety of Pain Conditions

By Pat Anson, Editor

A new medical device that uses electrical nerve stimulation was effective in managing chronic pain in patients suffering from arthritis, neuropathy, fibromyalgia and other conditions, according to a small clinical study conducted by NeuroMetrix (NASDAQ: NURO), the device’s manufacturer.

Pain News Network recently featured the Quell Wearable Pain Relief device in a column by J.W. Kain, who reported that Quell “worked brilliantly” in relieving her chronic neck and back pain.

Eighty eight people were enrolled in a 60-day trial of Quell. All had chronic pain for at least year and nearly a quarter had more than 15 years of pain. Participants had “complex medical histories” with arthritis (61%), diabetic nerve pain (40%), sciatica (27%), and fibromyalgia (26%) as the most common conditions.

Over 80 percent of the participants said Quell relieved their chronic pain and improved their overall health. The largest measured changes were in pain relief, along with improved sleep, general activity, and walking ability.

Over two-thirds of the patients said Quell also reduced the amount of pain medication they were taking

image courtesy of neurometrix

"We are pleased with these results. They represent the first formal evaluation of self-administered wearable intensive nerve stimulation. Quell provided substantial pain relief and improvement in quality of life measures,” said Shai N. Gozani, MD, President and CEO of NeuroMetrix.

“We were not surprised that two-thirds of the subjects reduced their use of pain medications, as we have consistently received this anecdotal feedback from Quell users over the past several months.”

Quell is available over-the-counter and does not require a prescription. It relieves pain by using electric stimulation to “mask” pain signals before they reach brain, much like a TENS unit.  The device, which costs $249, is lightweight and designed to be worn over the upper calf during the day or night.

The marketing of Quell for the treatment of chronic pain was approved by the Food and Drug Administration in 2014, but NeuroMatrix did not begin shipping the device to healthcare providers until this summer. It is also available through the company’s website.

A study abstract, “Treatment of Chronic Pain with a Novel Wearable Transcutaneous Electrical Nerve Stimulator,” has been accepted for poster presentation at the annual PAINWeek conference next month in Las Vegas.

Stress and Anxiety in RA Patients Leads to Heart Disease

By Pat Anson, Editor

In addition to pain and disability, rheumatoid arthritis patients often have to cope with depression, stress, anxiety, and lack of social support.

New research shows that toxic brew of emotions also makes them more likely to develop atherosclerosis, a buildup of fatty deposits in the arteries that leads to cardiovascular disease. The study, published in Arthritis Care & Research, recommends that RA patients be screened and treated for psychological issues to lower their risk of heart problems.

Rheumatoid arthritis is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing joint pain, inflammation and bone erosion. About 1.5 million Americans and 1% of adults worldwide suffer from RA.

Previous studies have shown that cardiovascular disease is more prevalent in RA patients, but until now the exact was unknown.

The new study looked at data from the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis Study (ESCAPE), which examined the prevalence, progression, and risk factors for cardiovascular disease in RA.

Nearly 200 RA patients underwent computed tomography and ultrasound tests to measure their coronary artery calcium (CAC) and carotid artery thickness for plaque build-up. Researchers found that patients with higher anxiety and anger scores, depression and caregiver stress were more likely to have high CAC scores – a sign of moderate to severe atherosclerosis.

"Our study shows that depression, stress, anxiety, and anger are associated with atherosclerosis markers, which are known predictors of cardiovascular risk in RA," said Dr. Ying Liu, the first author of the study. "These findings highlight the importance of screening and treatment of heart disease risks factors to limit not only health care costs, but prevent morbidity and mortality for RA patients."

Researchers also found that RA patients had an increased risk of carotid plaque buildup due to job stress. Having a strong social support network was linked to lower carotid artery thickness.

"Our study is the first to investigate the association between psychosocial comorbidities and elevated risk of atherosclerosis in RA patients," said  lead investigator Dr. Jon Giles, Assistant Professor of Medicine at Columbia University, College of Physicians & Surgeons in New York City. "Understanding the risk factors that lead to greater mortality in those with chronic conditions like RA is extremely important.”

A recent study by researchers in Mexico found that one quarter of patients with rheumatoid arthritis had ischaemia or infarction – decreased blood flow to the heart which can lead to a surprise heart attack.

“The condition nearly doubles the risk of a heart attack but most patients never knew they had heart disease and were never alerted about their cardiovascular risk," said Adriana Puente, MD, a cardiologist at the National Medical Center in Mexico City.

Many health experts believe the inflammation triggered by RA in the joints may raise inflammation throughout the whole body, including the heart’s coronary arteries.

According to the Arthritis Foundation, more than 50 percent of premature deaths in people with rheumatoid arthritis result from cardiovascular disease. The heightened risk of heart disease applies to all forms of arthritis, including osteoarthritis, gout, lupus and psoriatic arthritis.

New Drugs Could Relieve Neuropathy Pain

By Pat Anson, Editor

After more than a decade of study, researchers at Boston Children’s Hospital are close to developing a new class of non-narcotic drugs that relieve chronic nerve pain by targeting a protein that enhances pain and inflammation.

Their findings, reported in the journal Neuron, could lead to new treatments for diabetic peripheral neuropathy, post-herpetic neuralgia, and inflammatory diseases like rheumatoid arthritis. Current treatments provide meaningful pain relief in only about 15 percent of patients.

"Most pain medications that have been tested in the past decade have failed in Phase II human trials despite performing well in animal models," notes Clifford Woolf, MD, PhD, director of Boston Children's F.M. Kirby Neurobiology Center and a co-senior investigator on the study. "Here, we used human genetic findings to guide our search from the beginning."

Previous research by Woolf and his colleagues found that people with variants of the gene for GTP cyclohydrolase (GCH1) -- about 2 percent of the population -- are at markedly lower risk for chronic pain. GCH1 is needed to synthesize the protein tetrahydrobiopterin (BH4), and people with GCH1 variants produced less BH4 after a nerve injury. This suggested that BH4 regulates pain sensitivity.

To test their theory, researchers took a "reverse engineering" approach in genetic experiments on mice.  First they showed that mice with severed sensory nerves produce excess BH4, created by the injured nerve cells and by macrophages-- immune cells that infiltrate damaged nerves and inflamed tissue.

Mice that were genetically engineered to make excess BH4 had heightened pain sensitivity even when they were uninjured. Conversely, mice that were genetically unable to produce BH4 had lower pain hypersensitivity after a peripheral nerve injury.

"We then asked, if we could reduce production of BH4 using a drug, could we bring about reduction of pain?" said Alban Latremoliere, PhD, also of Boston Children's Kirby Center, who led the current study.

The answer was yes. The researchers blocked BH4 production using a specifically designed drug that targets sepiapterin reductase (SPR), a key enzyme that makes BH4. The drug reduced the pain hypersensitivity induced by nerve injury and without any detectable side effects.

Because BH4 plays an important role in the brain and blood vessels, the goal of any treatment would be to dial down excessive BH4 production, but not eliminate it entirely. Latremoliere showed that blocking SPR still allowed minimal BH4 production through a separate pathway and reduced pain without causing neural or cardiovascular side effects.

"Our findings suggest that SPR inhibition is a viable approach to reducing clinical pain hypersensitivity," says Woolf. "They also show that human genetics can lead us to novel disease pathways that we can probe mechanistically in animal models, leading us to the most suitable targets for human drug development."

Experimental RA Vaccine Shows Promise

By Pat Anson, Editor

Australian researchers have developed an experimental vaccine for rheumatoid arthritis (RA)  that could prevent the disease from developing in high-risk patients who have a genetic predisposition for RA.

In a small Phase I clinical study, researchers say the "Rheumavax" vaccine was safe and effective in suppressing the immune system response that triggers RA -- a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing swelling, inflammation and bone erosion. About 1% of adults worldwide suffer from RA.

"Current therapies only treat the symptoms and slow the progression of the disease,” said Professor Ranjeny Thomas of the University of Queensland Diamantina Institute. “We have designed a vaccine-style treatment or ‘immunotherapy’ specifically for individuals carrying high-risk rheumatoid arthritis genes and specific rheumatoid arthritis antibodies, called anti-CCP."

CCP antibodies are present in about 60% to 70% of people with RA and can be detected years before symptoms appear.

The personalized Rheumavax vaccine is made by taking a sample of each patient's blood and extracting an immune system cell called dendritic cells. Those cells are then challenged with a foreign peptide and an immune system modulator to create a vaccine that is then injected back into the patient.

Researchers say Rheumavax "teaches" the patient’s immune system to ignore a naturally occurring peptide that triggers the production of CCP antibodies that cause inflammation. In the study, 18 patients received a single injection of Rheumavax and one month later showed no signs of inflammation or RA disease flares.

“At this stage, the technique would not be ideal for widespread treatment or prevention of rheumatoid arthritis because it’s costly and time-consuming," said Thomas. “However, the promising results of this trial lay the foundations for the development of a more cost-effective, clinically-practical vaccine technology that could deliver similar outcomes for patients." 

"This research is such an exciting advancement for arthritis sufferers.  To know that someday in the future, hopefully the near future, there may be a treatment that actually treats the cause, not just the symptoms of rheumatoid arthritis, makes me very hopeful," said  Jennifer Martin, a rheumatoid arthritis sufferer and columnist for Pain News Network.  

"I often worry that my son could have inherited this awful illness from me and that one day he will begin to show symptoms.  To think that there may be a treatment that is effective very early on, or even before symptoms arise if they are able to detect the gene is very reassuring."

Professor Thomas says if Rheumavax proves successful treating RA, it could also be applied to other autoimmune diseases, such as Type 1 diabetes.  The study is published in the journal Science Translational Medicine. 

Until the late 1990s, one in three RA patients were permanently disabled within five years of disease onset. Although there are no cures for RA, in recent years there has been significant improvement in treatment, with disease control now possible for many patients who receive biologic drugs.

Poor Sleep Makes Osteoarthritis Worse

By Pat Anson, Editor

A new study is adding to the growing body of evidence linking poor sleep habits to chronic pain.

Researchers at Johns Hopkins University School of Medicine say patients with knee osteoarthritis (OA) who slept poorly had greater central sensitization -- which amplifies the amount of pain they feel. They are also more likely to catastrophize -- a clinical term meaning they were consumed by thoughts about pain.

Osteoarthritis is a joint disorder that leads to thinning of cartilage and progressive joint damage. Nearly 40 percent of Americans over the age of 45 have some degree of knee OA.

"Our study is the largest and most comprehensive examination of the relationship between sleep disturbance, catastrophizing and central sensitization in knee OA," said lead author Claudia Campbell, PhD, from the Department of Psychiatry & Behavioral Sciences at Johns Hopkins University School of Medicine. The study is published in Arthritis Care & Research.

The study included 208 participants who were categorized into four groups: OA patients with insomnia, OA patients with normal sleep habits, healthy controls with insomnia, and healthy controls without pain and normal sleep habits. Most of the participants were female.

Results showed that patients with knee OA and insomnia had the greatest degree of central pain sensitization compared to the controls. Researchers also found that patients with poor sleep and high catastrophizing scores reported higher levels of central sensitization -- which was associated with increased  pain.

"While no causal processes may be determined from this study, our data suggest that those with low sleep efficiency and higher catastrophizing have the greatest central sensitization. Understanding the intricate relationship between sleep, central sensitization, and catastrophizing has important clinical implications for treating those with chronic pain conditions such as knee OA," said Campbell.

A recent study in Norway found that getting a good night’s sleep plays a key role in determining how bad your pain levels are doing the day.  Those who had trouble sleeping at least once a week had a 52% lower pain tolerance. The study, which was published in the journal PAIN,  is the first to link insomnia and impaired sleep to reduced pain tolerance in a large, general population sample.  

A previous study in Norway found that women who have trouble sleeping are at greater risk of developing fibromyalgia.

Fatigue Often Stops RA Patients from Working

By Pat Anson, Editor

Fatigue and pain are the top reasons rheumatoid arthritis (RA) patients in the U.S. stop working, according to a new survey that found only about a third of RA patients are still employed full-time.

The “RA in America” survey of over 3,500 patients was conducted online by Health Union, a healthcare research and marketing company. It found that RA had a severe impact on patients’ quality of life, employment, and ability to afford treatment.

RA is a chronic and disabling autoimmune disease that causes pain and stiffness in joints. It affects about 1.3 million Americans and about one percent of the global population.

Ninety-four percent of respondents said they cannot do as much as they were able before acquiring the disease. Only 37% said they were still working full time.

Although fatigue is often overlooked as a symptom of RA, it had the greatest impact on the respondents’ ability to work – with 92% reporting they were tired while on the job. Pain, physical limitations, and a lack of understanding by colleagues also presented challenges.

“My biggest complaint is fatigue,” wrote one poster on a Health Union Facebook page.  “I am an invalid due to RA. I am in bed 24/7, I can't even sit up. I sleep a lot, not much else to do, but no matter how much I sleep, when I wake I'm exhausted. It's so crazy. I can sleep for 20 hours, and I'm exhausted the minute I open my eyes.”

“I was forced from my job because of exhaustion,” wrote another woman. “The meds contributed to the sleepiness, so I am careful about which I take. (I have) developed Lupus, OA and several related syndrome in addition to the RA.”

Many people who were surveyed said they were diagnosed with other conditions, including depression and anxiety (39%), high blood pressure (33%), fibromyalgia (32%) and migraine (25%).

Survey respondents also reported they needed help with daily activities, such as cleaning (75%) and other household chores (52%). Over a third (41%) needed assistance from a caregiver, which was typically a spouse, to help manage their RA.

"Many people do not know rheumatoid arthritis is a progressive, autoimmune disease and not the result of aging and wear on the body, like osteoarthritis the most common form of arthritis," said Andrew Lumpe, PhD, an RA patient. "Treatment can help slow the damage, but rheumatoid arthritis frequently alters the lives of both patients and their families."

The survey found some good news to report. Over a third (34%) of respondents said their RA had gone into remission at some point, usually for less than a year. Nearly three-fourths (74%) said the remission occurred after they began taking medication.

About half the survey respondents reported satisfaction with their treatments and only 21% were dissatisfied. Those on biologics, a newer and more expensive medication that can cost over $20,000 a year, had a slightly higher satisfaction rate. Over a third of respondents (38%) have avoided medications because of cost.

"The affordability of effective rheumatoid arthritis treatments is a serious concern," said Mariah Leach, an RA patient. "When you consider the burden this disease places on patients in terms of quality of life and employment, it is clear that supporting these individuals with treatment options can yield many benefits."

New Arthritis Treatment Could Slow Joint Damage

By Pat Anson, Editor

Researchers in California are working on a novel method for the treatment of rheumatoid arthritis that could open the door to a new class of medications that prevent joint damage.

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing pain, inflammation and bone erosion. Most RA treatments focus on suppressing the immune system to reduce inflammation and slow progression of the disease.

"Unfortunately, for around 40 percent of patients, immune-targeted therapies are not sufficient to bring them into full remission," said Nunzio Bottini, MD, an associate professor at the La Jolla Institute for Allergy and Immunology and associate professor of Medicine at the University of California, San Diego.

"If we could add a drug that acts on a different target without increasing immune suppression it could be very valuable."

Bottini and his colleagues are focusing on specialized cells called fibroblast-like synoviocytes (FLS) that line the inside of joints, providing lubrication and repairing joint injuries. In RA patients, the cells invade surrounding cartilage and secrete enzymes that break down the rubbery tissue that cushions the bone. They also trigger bone destruction.

"Even if your inflammation is completely under control with the help of current therapies -- and they are excellent -- the damage to the skeletal structure is not necessarily arrested in the long term because synoviocytes continue to cause damage," explains Bottini. "And although synoviocytes are considered the main effectors of cartilage damage in rheumatoid arthritis there's no therapy directed against them."

FLS cells rely on phosphates to transmit signals. When researchers screened tissue samples from rheumatoid arthritis patients for the expression of phosphatases, they discovered that an enzyme called RPTPσ -- short for receptor protein tyrosine phosphatase sigma -- is highly expressed on the surface of their FLS cells. RPTPσ weakens the ability of synoviocytes to aggressively invade the joint's cartilage.

"RPTPσ acts like an inhibitory signal that is pre-coded on the surface of these cells," says postdoctoral researcher Karen Doody, PhD, first author of the study published in Science Translational Medicine.

“Being able to activate RPTPσ's activity gives us a specific tool with which to adjust the migration and aggressiveness of synoviocytes in rheumatoid arthritis," said Doody, who hopes to develop drugs that make the cells less invasive and lose their ability to attach to cartilage.

"The ultimate goal is to use biologics that target synoviocytes in combination with treatments that suppress the immune system, such as methotrexate or anti-TNF, to address all three aspects of rheumatoid arthritis: swollen joints as a result of inflammation, cartilage damage and bone damage."

About 1.5 million Americans and 1% of adults worldwide suffer from RA.

Older Men Less Likely to Be Screened for Osteoporosis

By Pat Anson, Editor

Elderly men are far less likely to be screened for osteoporosis or to take preventive measures against the bone-thinning disease than women, according to the results of a new study.

"We were surprised at how big a difference we found between men and women regarding osteoporosis," said Irina Dashkova, MD, lead author of the study, which is being presented at The American Geriatrics Society's annual meeting in Washington, DC. "In our environment, you just get this perception that osteoporosis is a women's problem. This has to be changed, and the sooner the better.

More than 10 million Americans suffer from osteoporosis, which raises their risk for serious bone fractures.  About 2 million are men -- and another 8 to 13 million men have low bone mineral density, a precursor to osteoporosis. Previous studies have found that 13% of white men over the age og 50 will experience at least one osteoporosis-related fracture during their lifetime.

“We know from research that when men suffer fractures, their mortality is higher than in women and that severe medical consequences and loss of independence are much more prevalent in men,” said Dashkova.

The risk of death after sustaining a hip fracture is twice as high in men compared to women, and loss of independence is also more common in males. Some medical conditions and drugs that can raise the risk of osteoporosis are male-specific, such as prostate cancer drugs that affect the production of testosterone.

Dashkova and her colleagues at North Shore-LIJ Health System surveyed 146 older men and women in New York and Florida and found “stunning” gender differences in attitudes and beliefs about osteoporosis:

• Women were far more likely to report a family history of osteoporosis (nearly 91% compared to 9%)
• Most women would accept osteoporosis screening, while less than 25% of men would
• Women were 4 times more likely to take preventive measures against osteoporosis, such as taking calcium and vitamin D supplements

Part of the problem may be that healthcare providers aren't encouraging men to undergo screening as often as they should.

"Our survey clearly establishes that physicians are just not thinking of screening men. It's only when older men fall and break their hip that someone thinks maybe we should do something to prevent them breaking the other hip," said Gisele Wolf-Klein, MD, director of geriatric education for the North Shore-LIJ Health System. "Not only is society in general unaware of the problem of osteoporosis in men, men are not seeking screening and diagnosis.

"The average age in my practice is in the 90s, and our patients are to be congratulated because clearly they're doing something right. But we have a duty to make sure those later years are as happy and productive as can be and not spent in a wheelchair."

Rheumatoid Arthritis Raises Risk of Heart Attack

By Pat Anson, Editor

Rheumatoid arthritis is a painful, disabling and incurable disease of the joints. But what many RA patients don’t know is that it also significantly raises their risk of a heart attack.

A new study by researchers in Mexico found that one quarter of patients with rheumatoid arthritis and no prior symptoms of heart disease could have a surprise heart attack. Their risk was higher even without cardiovascular risk factors such as smoking and diabetes.

“The condition nearly doubles the risk of a heart attack but most patients never knew they had heart disease and were never alerted about their cardiovascular risk," said  Adriana Puente, MD, a cardiologist at the National Medical Center in Mexico City.

Rheumatoid arthritis is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing swelling, inflammation and bone erosion. About 1% of adults worldwide suffer from RA.

Dr. Puente’s study, which was presented this week at the International Conference of Nuclear Cardiology in Madrid, involved 91 RA patients with no prior symptoms of heart disease. Ninety percent of the patients were women, their average age was 59, and they had similar cardiovascular risk factors as the general population.

Nearly one quarter of the patients (24%) had abnormal Gated SPECT, indicating the presence of ischaemia or infarction – decreased blood flow to the heart which can lead to the death of heart tissue.

"The ischaemia and infarction may be explained by the persistence of the systemic inflammation in rheumatoid arthritis which may cause an accelerated atherosclerosis process,” said Puente.

"The results highlight the importance of conducting diagnostic tests in patients with rheumatoid arthritis to see if they have cardiovascular disease, specifically atherosclerotic coronary artery disease (ischaemia or myocardial infarction) even if they have no symptoms and regardless of whether they have cardiovascular risk factors.”

Puente says patients should be warned that some RA medications, such as corticosteroids and methotrexate, can elevate plasma lipid levels and raise their risk of cardiovascular disease.

"Patients with rheumatoid arthritis should be told that they have an elevated predisposition to heart disease and need pharmacological treatment to diminish the inflammatory process and atherosclerotic complications. They also need advice on how best to control their rheumatoid arthritis and decrease their cardiovascular risk factors,” she said

Many health experts believe the inflammation triggered by RA in the joints may raise inflammation throughout the whole body, including the heart’s coronary arteries.

According to the Arthritis Foundation, more than 50 percent of premature deaths in people with rheumatoid arthritis result from cardiovascular disease.

But the heightened risk of heart disease applies to all forms of arthritis, including osteoarthritis, gout, lupus and psoriatic arthritis.

“Inflammation, regardless of where it comes from, is a risk factor for heart disease,” says rheumatologist Jon T. Giles, MD, assistant professor of medicine at Columbia University School of Medicine. “So it’s not surprising that people with inflammatory arthritis like RA, lupus and psoriatic arthritis have more cardiac events.”

Injectable Gel Could Help Knee Cartilage Heal

By Pat Anson, Editor

With the number of knee replacement surgeries soaring in the United States, researchers at the University of Iowa are working on an injectable gel that could repair damaged cartilage and make many knee surgeries unnecessary.

"We are creating an [injectable, bioactive] hydrogel that can repair cartilage damage, regenerate stronger cartilage, and hopefully delay or eliminate the development of osteoarthritis and eliminate the need for total knee replacement," says Yin Yu, a graduate student at the University of Iowa (UI) whose study is featured in the journal Arthritis and Rheumatology.

Osteoarthritis (OA) is a joint disorder that leads to thinning of cartilage and progressive joint damage. Nearly 40 percent of Americans over the age of 45 have some degree of knee OA, and those numbers are expected to grow as the population ages.

About 600,000 knee replacement surgeries are performed annually in the U.S. – about twice the number performed 20 years ago. Recent studies have questioned whether many of the surgeries are appropriate.

UI researchers have previously identified precursor cells in healthy cartilage that can mature into new cartilage tissue – a surprising development given the long-held assumption that cartilage is one of the few tissues in the body that cannot repair itself.

The researchers also identified molecular signals that encourage precursor cells to migrate out of healthy tissue and into damaged areas – stimulating the development of new cartilage. One of the signals, called stromal cell-derived factor 1 (SDF1), acts like a “homing beacon” for the precursor cells.

In an experimental model of cartilage injury, Yu loaded the hydrogel with SDF1 and injected it into holes punched into the model cartilage. The precursor cells migrated toward the SDF1 infused gel and filled in the injury site. Subsequent application of a growth factor caused the cells to mature into normal cartilage that repaired the injury.

The new tissue is not as strong as normal cartilage, but researchers think it could be strengthened through physical therapy and exercise.

"There's really no cure for osteoarthritis except for total joint replacement, which is not particularly suitable for younger patients because the artificial joints wear out and need to be replaced multiple times," said James Martin, PhD, a UI assistant professor of orthopedics and rehabilitation who leads the research team.

"Our approach aims to leverage the body's own capacity for repair, and what we've shown is that cartilage does have regenerative potential; you just have to manipulate it just right."

UI Researchers are now looking at different ways to include the growth factor in the hydrogel – possibly by using nano-size plasmids that carry genetic instructions for the growth factor or microspheres loaded with the substance.

Yu and Martin plan to start animal trials within a year and, if the results are promising, begin human trials in about five years.

Injections of platelet rich plasma (PRP) into the knee also show promise in the treatment of osteoarthritis, according to a recent study published in The Journal of the American Osteopathic Association (JAOA).

Only a few small clinical trials have been conducted on the effectiveness of PRP therapy. Researchers at the University of Miami Miller School of Medicine analyzed those trials and found that patients with knee osteoarthritis and other musculoskeletal injuries showed significant improvements as long as two years after PRP injections.

The procedure involves withdrawing blood from the patient and then spinning it to produce a high concentration of platelet cells. The plasma is then injected back into the patient at the injury site, speeding up the healing process. Several top athletes, including Kobe Bryant and Peyton Manning, have used a form of PRP therapy to help them recover from injuries.

Doctor Defends Use of Urine Drug Tests

By Pat Anson, Editor

A prominent pain doctor is disputing reports that a widely used urine drug test often gives faulty results.

“They are reasonably reliable and highly cost effective for use in a pain management practice. I would strongly recommend the practitioners use this,” said Laxmaiah Manchikanti, MD, chairman and CEO of the American Society of Interventional Pain Physicians.

Dr. LAXMAIAH MANCHIKANTI

Dr. Manchikanti, who is medical director of a pain clinic in Paducah, Kentucky, was the lead author of a study published in the journal Pain Physician in 2011, which looked at the reliability of immunoassay “point-of-care” (POC) tests. The urine tests are inexpensive and give immediate results, and doctors often use them to monitor their patients for opioid or illicit drug use.

“The UDT (urine drug test) with immunoassay in an office setting is appropriate, convenient and cost effective. Compared with laboratory testing for opioids and illicit drugs, immunoassay office testing had high specificity and agreement,” Manchikanti's study found.

Pain News Network recently reported on the results of a second study conducted by Millennium Health, a San Diego-based drug testing laboratory, which found that POC tests were wrong about half the time – frequently giving false positive and false negatives results for drugs like marijuana and oxycodone. The Millennium study advocates the use of chromatography-mass-spectrometry – a more complex laboratory test that costs thousands of dollars – to confirm POC test results.

“Following the advice from companies in reference to numerous expensive tests and also income generating avenues will only lead to time in the slammer and will not improve patient care at all,” said Manchikanti.

“(The) Millennium study is performed by the company which makes a living by testing. The more samples that are sent to them, the better off they are. Further, they are not even a practical setting. From our practice we send approximately only 2% of the samples for confirmation testing. Even then, the patients can’t pay their bills.”

Manchikanti’s study found false negative and false positive rates for POC tests that were far below the rates reported by Millennium.

For example, Millennium’s false positive rate for oxycodone was 41.3 percent. For Manchikanti, it was only 7.7 percent.

Millennium’s false positive rate for marijuana was 21.3 percent. For Manchikanti, it was just 2 percent.

There were discrepancies between the two studies for several other drugs, including methadone, cocaine and methamphetamine.

Millennium Sponsored Both Studies

How could two studies come to such different conclusions?

There were some differences in their design. Urine samples in the Millennium study came from nearly 4,300 patients in addiction treatment clinics, while the urine samples in Manchikanti’s study came from 1,000 patients in pain management programs. Millennium maintains the patients in its study were younger and more likely to be drug users.

Ironically, the laboratory tests for both studies were conducted by Millennium – which collected samples and provided chromatography-mass-spectrometry testing at no cost to Manchikanti. Millennium is identified as the “sponsor” of Manchikanti’s study, but he says the company had “no influence or interference” in his and his three co-authors’ findings.

“We had our agreement in the beginning itself that they will not be involved in any way in writing the manuscript or publishing the results. Consequently, they really did not have much input into the publication. The publication was as it is and without any bias from the industry,” Manchikanti wrote in an email to Pain News Network.

Millennium’s study, which was published last year in the Journal of Opioid Management, had six co-authors. All but one were employees of the company. The lone exception is a pain management doctor who frequently testifies as a legal expert for Millennium in court cases.

A source with broad experience in the drug testing industry told Pain News Network the data in Millennium’s study was “skewed toward exaggeration.”

“It does not surprise me that Millennium would show a high rate of inconsistencies with the POC test. Remember, their business is to sell confirmation testing, so they will skew the way they present data to try to influence the market to do more confirmation testing.  In most cases, that’s how it works in any study conducted or funded by a device or pharmaceutical company,” the source said.

Millennium bristles at the notion that its study was biased.

“Millennium Health strongly disagrees with the characterization… that the study was skewed or biased in any way,” the company said in a statement to Pain News Network.

“The study was accepted and published by a well-respected, peer-reviewed publication. Millennium Research Institute is committed to the highest ethical and research science standards, and we stand by the results of our study. The study was based on random samples from addiction treatment clients. The data clearly indicated that immunoassay, or point-of-care, tests have a high rate of false positives and false negatives when used to screen patients for illicit drug use.

“Millennium is committed to providing data that helps clinicians evaluate the best course of treatment for patients with pain and addiction issues. Millennium Health performs only the tests ordered by clinicians.”

In recent years a growing number of doctors who treat addicts and pain patients have required them to submit to drug tests. The competition between Millennium and other laboratories for this business is intense. According to one estimate, drug testing has grown into a lucrative $4 billion dollar a year industry.

But Manchikanti maintains that a single inexpensive urine test that costs about $20 is often the only one that’s needed.

“If a proper (patient) history is provided which matches with the test, there is no need for further testing,” he said.

Miss Understood: Surgery is a Big Deal

By Arlene Grau, Columnist

A few weeks ago I had my first scheduled surgery, a synovectomy of the right wrist, to repair some of the damage caused by rheumatoid arthritis to my wrist joint.

I've had numerous surgeries in the past, but none before were the result of my auto immune diseases. I was first diagnosed 7 years ago, at the age of 22.  

It wasn't until I met with my orthopedic surgeon that I realized this may be the first of many surgeries I may need. I just didn't expect to need one when I was still in my 20's.

I guess you could say that there are many misconceptions when it comes to what pain sufferers have to endure and what the timeline is for everything because no two people are alike.

When I told people about the procedure I would be having, some of them were compassionate and offered help if I needed it during recovery. Others assumed I would be on my feet and back to normal within the first week. I only knew what I was being told by my surgeon -- and to me it was a big deal.

The type of surgery itself isn't dangerous, but I was more concerned with the fact that I would only have the use of my left arm while I recovered. Not only that, I had a nerve block to help me deal with the pain. This meant that for the first week I wouldn't be able to feel my right arm and I would have no control over it.

ARLENE GRAU

I had asked several friends for help with dinner, since I was unable to cook, and to my surprise the people who were the busiest and I hadn't seen in some time came to my aid.

Still, I felt like most people thought the surgery wasn’t very invasive and I probably had very small incisions, which meant I shouldn't be in much pain. Maybe they thought I was trying to milk my situation and get sympathy, but that was never the case.

I decided to post a picture of my wrist after my first cast was removed, something I regularly do when I have procedures done, because I want people to understand what I go through and get it through their heads that I'm not making up the fact that I'm in pain all the time.

It's easy for others to say, "Don't worry about what they think" or "Turn the other cheek." But it's hard to do when you're constantly being judged. The worst part is that at times it's by the people you love the most.

To say that surgery for someone who has chronic pain is no big deal is far from the truth. My fibromyalgia is a magnet for pain and as soon as I woke up from surgery, I began to scream in agony. Yes, the nerve block numbed the pain in my arm, but the rest of my body went crazy.

I felt like I had been in a terrible accident. Any type of procedure or even a regular checkup is painful when it involves another person pressing on the areas where you feel the most amount of pain.

To assume everyone heals the same way is ignorant. Some people would rather believe that though, because it excuses them from having to show compassion towards those of us who suffer on a day-to-day basis.

Arlene Grau lives in southern California with her family. She suffers from rheumatoid arthritis, fibromyalgia, lupus, migraine, vasculitis, and Sjogren’s disease.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represent the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Cost of RA Drugs a 'Significant Financial Burden'

By Pat Anson, Editor

Over the last decade great strides have been made in the treatment of rheumatoid arthritis (RA), but the cost of treating the disease with new biologic drugs has become a “significant financial burden” for many patients.

According to a new study published in Arthritis & Rheumatology, RA patients enrolled in Medicare Part D plans paid an average out-of-pocket cost of $835 a month for a biologic disease modifying drug (DMARD) in 2013. Costs varied widely depending on the drug – from $269 a month for the biologic infliximab to $2,993 a month for anakinra.

Costs remained high because the vast majority of Part D plans required RA patients to pay about a third of the cost of DMARD drugs, rather than a fixed dollar co-pay amount. In addition, catastrophic coverage under Part D didn’t kick in until out-of-pocket costs reached $4,450, after which patients paid 5% of the cost of DMARD drugs.

The financial burden is too much for many patients. According to a previous study, 1 in 6 adults with RA decreased their medication because of cost.

"While specialty DMARDs have improved the lives of those with chronic diseases like RA, many patients face a growing and unacceptable financial burden for access to treatment," said lead author Jinoos Yazdany, MD, with the Division of Rheumatology at the University of California, San Francisco (UCSF).

"Rather than determining which drug is best for the patient, we find ourselves making treatment decisions based on whether patients can afford drugs.”  

Rheumatoid arthritis is a chronic and incurable autoimmune disease that causes pain and stiffness in joints. Until the late 1990s, one in three RA patients were permanently disabled within five years of disease onset. In recent years there has been significant improvement in RA treatment, with disease control now possible for many patients who receive DMARD therapy.

Treatment with DMARDs is now a standard component of care with costs for some of the newer drugs topping $20,000 annually. A recent report by GBI Research estimates that the U.S. market for RA treatment will increase from $6.4 billion in 2013 to $9.3 billion by 2020, driven in part by an increase in the number of patients with RA – which is expected to grow from 1.3 million Americans to 1.68 million by 2020.

The UCSF study analyzed Medicare Part D coverage of nine biologic medications (abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab, tocilizumab) and nine non-biologic DMARDs (azathioprine, cuprimine, cyclophosphamide, cyclosporine, hydroxychloroquine, leflunomide, methotrexate, minocycline, and sulfasalazine).

Although nearly all Part D plans covered at least 1 biologic DMARD, access was tightly controlled, with 95% of plans requiring prior authorization.

Researchers said implementation of the Affordable Care Act (Obamacare) will not significantly lessen the cost of biologic drugs.

"Many patients are strapped with a substantial financial burden," said Yazdany. “Clinicians caring for individuals with RA should be aware of this and be prepared to discuss long-term affordability as well as relative efficacy of biologic DMARDs with their patients to help them make informed decisions about treatment. Currently, cost discussions occur in only one-third of RA office visits where changes are made to RA drug treatment.”

One alternative is the use of non-biologic DMARDs, such as methotrexate, which were once the standard treatment for RA. Both Medicare Advantage plans and PDP plans cover nearly all non-biologic DMARDs, with most charging fixed dollar co-pays that averaged $4 to $34 a month.

Researchers in Belgium recently found that a combination of older generic drugs (methotrexate, sulfasalazine and leflunomide) treated RA in its early stages just as effectively as biologics, but with less medication, fewer side effects, and at a significantly lower cost.

A similar study published in the New England Journal of Medicine found that RA patients who took three oral generic drugs (methotrexate, sulfasalazine and hydroxychloroquine) saw just as much improvement in their symptoms as those who used methotrexate and Enbrel, an injectable biologic sold by Amgen.

The average annual cost of the three drug therapy was about $1,000, compared to about $25,000 per year for Enbrel.

When Your Body Betrays You

By Jennifer Martin, Columnist

I remember very vividly the day I first began thinking about how much my body has betrayed me. It wasn’t too long after I got home from spending nearly six weeks in the hospital.  I was recovering from my first j-pouch surgery. 

I was sitting on the couch at my mother and stepfather’s house, feeling depressed, weak and hopeless.  I couldn’t see the light at the end of the tunnel.  These were emotions I had not experienced to this extent before; even after the years of ups and downs I had had living with rheumatoid arthritis and ulcerative colitis.

I remember my mom telling me, “You need to work through these feelings of depression.  We need to get you out of the house.  Staying inside all day isn’t going to help.  Let’s go to the harbor so you can at least sit outside and be around people.”

My husband told me, “You need to fight.  I can’t fight for you if you are going to give up.”

My stepdad said to me, “You are strong.  I know you can get through this.  We are all here for you.”

While I appreciated all of these sentiments, all I wanted to do was scream at them, “You have no idea what I need!  I am not strong!  I don’t want to do this anymore!” 

And I wanted to scream at my body, “How could you do this to me? Why are you doing this to me?” 

I had never felt so lost and confused.  And I had never felt so betrayed by my own body, which at the time struck me as odd, seeing as I had been living with chronic illness and pain my whole life.

What I eventually learned from that horrible day was that my family was right.  The only way you can begin to resolve these feelings of body betrayal is to do something about it;  to learn to cope with your chronic pain or chronic illness, even if you don’t want to. 

Trust me, the last thing I wanted to do that day was to go out in public looking as sick as I did and feeling like I was about to collapse.  I had no idea how I was even supposed to make it from the car to the nearest bench to sit down.  But I did, and while I’m not going to claim that it fixed everything, it did help my mood somewhat. 

At that time I was angry at my husband because I felt like he was putting a lot of pressure on me.  I felt like in order to fight I had to put on a happy face all of the time and that I was not allowed to experience my pain or sorrow in front of him.  

After giving what he said some thought however, I realized what he meant.  He didn’t mean that I was never allowed to feel sorry for myself and he didn’t mean that I was never allowed to complain or cry. 

What he meant was that I was the only one who had control over how I dealt with my situation and the upcoming struggles I was still to have.  I could either  give in and give up or I could find a way to work through what I was going through.  He couldn’t do that for me.

I remember wanting to tell my stepdad that I felt the complete opposite of strong.  I also remember feeling guilty for the support my family was giving me.  I felt like a burden and I didn’t want them to give up so much just for me.  It didn’t feel fair and it didn’t feel right that just because I was going through something so terrible they had to go through it with me. 

Looking back on my experience, I realize how lucky I was and still am to have that kind of support.  It is so important for those experiencing chronic pain or chronic illness to have a support system, whether it is one friend, a support group or a whole clan of people.

I have learned that all you can do in those moments when you feel your body has betrayed you is do what you can.  We don’t have control over the chronicity of our conditions.  However, as much as it doesn’t seem like it at times, we do have control over how we choose to approach our condition. 

We can learn to cope by:

• participating in enjoyable activities when we feel well
• advocating for our health
• taking our medications
• getting help when we feel depressed or anxious
• exercising when we have the energy and aren’t in too much pain
• making sure we aren’t isolating ourselves from friends and family
• resting when we do not feel well
• focusing on the positive things in our lives
• learning to manage the guilt we may feel

We can give in to all of the negative thoughts, or we can learn how to combat negative thinking.

We can let our pain or illness define us or we can learn how not to let that happen.

We can give in and give up, or we can fight. 

Jennifer Martin, PsyD, is a licensed psychologist in Newport Beach, California who suffers from rheumatoid arthritis and ulcerative colitis. In her blog “Your Color Looks Good” Jennifer writes about the psychological aspects of dealing with chronic pain and illness. 

Jennifer is a professional member of the Crohn’s and Colitis Foundation of America and has a Facebook page dedicated to providing support and information to people with Crohn’s, Colitis and Digestive Diseases, as well as other types of chronic pain.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.