Use of NSAIDs Risky for Osteoarthritis Patients

By Pat Anson, PNN Editor

It’s long been known that nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen can raise the risk of cardiovascular problems. A large new study in Canada has documented how NSAIDs can significantly raise the risk of heart disease, congestive heart failure and stroke in people with osteoarthritis.

Osteoarthritis (OA) is a joint disorder that leads to thinning of cartilage and progressive joint damage. NSAIDs are frequently used to treat the pain and inflammation caused by OA.

The Canadian study, published in the journal Arthritis & Rheumatology, looked at nearly 7,750 osteoarthritis patients in British Columbia and compared them with a control group of over 23,000 patients without OA. The average age of the participants was 65 and a little over half were women.

The risk of developing cardiovascular disease was found to be about 23% higher among people with OA than the control group. Researchers attributed about 41% of that increased risk to the use of NSAIDs.

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NSAIDs appeared to play a significant role in several cardiovascular problems. The risk of congestive heart failure was 42% higher among people with OA, followed by a 17% greater risk of heart disease and a 14% greater risk of stroke.

"To the best of our knowledge, this is the first longitudinal study to evaluate the mediating role of NSAID use in the relationship between osteoarthritis and cardiovascular disease in a large population-based sample," said senior author Aslam Anis, PhD, of the School of Population and Public Health at the University of British Columbia.

"Our results indicate that osteoarthritis is an independent risk factor for cardiovascular disease and suggest a substantial proportion of the increased risk is due to the use of NSAIDs. This is highly relevant because NSAIDs are some of the most commonly used drugs to manage pain in patients with osteoarthritis."

The association of cardiovascular disease with NSAIDs is consistent with previous research.  A large international study in 2017, for example, found that prescription strength NSAIDs raises the risk of a heart attack as soon as the first week of use.

NSAIDs are used to alleviate pain and reduce inflammation, and are found in a wide variety of over-the-counter products, including cold and flu remedies. They are found in so many products -- such as Advil and Motrin -- that many consumers may not be aware how often they use NSAIDs. 

Canada adopted guidelines in 2017 that recommend NSAIDs as an alternative to opioid pain medication. The guideline makes no mention of the health risks associated with NSAIDs, but focuses on their cost effectiveness.

“NSAID-based treatment may have lower mean costs and higher effectiveness relative to opioids,” the guideline states. “Naproxen-based regimens in particular may be more cost effective compared to opioids and other NSAIDs, such as ibuprofen and celecoxib.”

Opioid guidelines released in 2016 by the U.S. Centers for Disease Control and Prevention also recommend NSAIDs as an alternative to opioids, but acknowledge the medications “do have risks, including gastrointestinal bleeding or perforation as well as renal and cardiovascular risks.”

In 2015, the Food and Drug Administration ordered warning labels for all NSAIDs to indicate they increase the risk of a fatal heart attack or stroke. The FDA warning does not apply to aspirin.

The European Society of Cardiology recommends limited use of NSAIDs by patients who are at risk of heart failure. People already diagnosed with heart failure should refrain from using NSAIDs altogether.

The Hidden Benefits of Glucosamine

By Pat Anson, PNN Editor

Do you take glucosamine supplements to reduce joint pain and stiffness? You’re not alone if you do. According to a 2007 survey, nearly 20 percent of U.S. adults take glucosamine to prevent or treat pain from osteoarthritis, back pain and other conditions.

The evidence to support the use of glucosamine for joint pain is thin, but a large new study in The BMJ suggests regular use of the supplement can reduce the risk of cardiovascular disease.

Researchers at Tulane University analyzed 7 years of extensive health data for almost half a million adults aged 40 to 69 enrolled in the UK Biobank study. Those who regularly took glucosamine were about 15% less likely to develop heart disease or have a stroke.

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Glucosamine occurs naturally in the fluid around joints and plays an importantly role in building cartilage. Glucosamine is extracted from shellfish and is often combined in supplements with chondroitin, a similar substance that is also found in joints.

People who took glucosamine in the BMJ study were more likely to be women, older, more physically active, have healthier diets and take other supplements.

Over the course of seven years, 2.2% of those who did not use glucosamine had a heart attack or stroke, compared to 2.0% of people who did use glucosamine. People who used glucosamine were also less likely to die from a heart attack or stroke, 0.5% vs. 0.7% of those who didn’t use the supplement.

The difference doesn’t appear to be significant, but when adjusted for risk and other factors, it means that glucosamine users had a 22% lower risk of dying from a heart attack or stroke.

For smokers, the benefits of regular glucosamine use were even greater. They had 37% less risk of having coronary heart disease compared to smokers who didn’t use the supplements.

Researchers didn’t establish the reason why glucosamine lowers the risk of cardiovascular disease (CVD), but they believe the supplements help reduce inflammation – one of the main factors involved in the development of heart disease, as well as chronic pain.

“Several potential mechanisms could explain the observed protective relation between glucosamine use and CVD diseases. In the National Health and Nutrition Examination Survey (NHANES) study, regular use of glucosamine was associated with a statistically significant reduction in C reactive protein concentrations, which is a marker for systemic inflammation,” researchers reported. “Other mechanisms might also be involved, and future investigations are needed to explore the functional roles of glucosamine in cardiovascular health.”

The UK’s National Health Service (NHS) downplayed the study findings, pointing out the cardiovascular benefits of glucosamine are “quite small.”

“If you want to reduce your risk of having a heart attack or stroke, it would be much better to concentrate on living a healthy lifestyle, rather than paying for glucosamine supplements,” the NHS said.

New Safety Concerns for Osteoarthritis Drug

By Pat Anson, PNN Editor

Disappointing results from a Phase 3 clinical study are raising new safety concerns about an experimental class of pain-relieving drugs once considered a promising alternative to opioids.

Pfizer and Eli Lilly say 6.3% of osteoarthritis patients taking a 5 mg dose of tanezumab experienced rapidly progressive osteoarthritis in their joints. There was significant improvement in their pain and physical function, but the patients’ overall assessment of their condition was no better than those treated with non-steroidal anti-inflammatory drugs (NSAIDs).

Patients taking a lower 2.5 mg dose of tanezumab did not have any significant improvement in their pain, quality of life or overall condition. And 3.2% experienced rapidly progressive osteoarthritis.

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“We are analyzing these findings in the context of the recent Phase 3 results as we assess potential next steps for tanezumab,” Ken Verburg, Pfizer Global Product Development, said in a statement. “We plan to review the totality of data from our clinical development program for tanezumab with regulatory authorities.”

Tanezumab is a humanized monoclonal antibody that targets nerve growth factor (NGF), a protein that increases as a result of injury, inflammation or chronic pain. Tanezumab binds to NGF and inhibits pain signals from reaching the brain.

Tanezumab was considered so promising a therapy that it was given fast track designation from the FDA in 2017, a process that speeds up the development of new therapies to treat serious conditions.

Ironically, it was the FDA that slowed the development of NGF inhibitors in 2010 because of concerns that tanezumab made osteoarthritis worse in some patients. Most clinical studies of tanezumab did not resume until 2015.

The reappearance of the same safety issue and the marginal pain relief provided by tanezumab could be the last straw for the drug, according to one analyst.

“It is hard for us to imagine how these results could have been much worse. Pfizer indicated that they ‘plan to review the totality of data’ with regulatory authorities, which suggests to us that the co-sponsors will try to find a way to resurrect the program for some subset or sub-population of patients, but recognizes that this result puts the drug’s entire future in doubt,” SVB Leerink research analyst Geoffrey Porges said in a note to clients.

A clinical study of fasinumab, another NGF inhibitor being developed by Teva and  Regeneron Pharmaceuticals, was stopped by the FDA in 2016 after a patient showed signs of severe joint disease. Regeneron and Teva are continuing to study fasinumab in patients with chronic low back pain.

Pfizer and Eli Lilly are also studying tanezumab as a treatment for low back pain, and reported promising results from a Phase 3 trial in February. Rapidly progressive osteoarthritis was also reported in a small number of patients involved in that study.

Stem Cells Reduce Pain from Knee Osteoarthritis

By Pat Anson, PNN Editor

A small new study has demonstrated that stem cells collected from a patient’s own bone marrow can significantly reduce pain caused by osteoarthritis of the knee.

In the first clinical trial of its kind in Canada, researchers collected mesenchymal stromal cells (MSCs) from the spines of 12 middle-aged patients with moderate to severe knee osteoarthritis. These “autologous” cells – stem cells derived from a patient’s own fat or bone tissue – were then processed and injected back into the patients’ knees at different doses.

Researchers then followed the patients for the next 12 months, using MRI imaging, biomarkers, molecular fingerprinting and the patient's own assessment of how they felt.

"Our goal was to test for safety as well as to gain a better understanding of MSC dosing, mechanisms of action and donor selection," said lead author Sowmya Viswanathan, PhD, Arthritis Program at the Krembil Research Institute, University Health Network in Toronto.

At the end of the study period, researchers said there were significant improvements in all 12 patients’ pain levels, stiffness and quality of life. The study also showed that the MSCs were safe at all the doses tested and that the higher the dose, the more effective the outcome.

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"We also obtained novel insights into a potential anti-inflammatory mechanism of action of these cells in osteoarthritic knee joints. We noted that donor heterogeneity is an important factor, and our assembled panel of genes helps us identify cells which are potent in osteoarthritis. These are important findings which we hope to translate into a larger, powered clinical trial as part of our next steps," said Viswanathan, who reported the findings in the journal Stem Cells Translational Medicine.

Over 250 million people worldwide suffer from knee osteoarthritis (OA), which causes thinning of cartilage and progressive joint damage. Nearly 40 percent of Americans over the age of 45 have some degree of knee OA.

Knee replacement and arthroscopic knee surgeries are commonly used to treat knee OA, even though many studies show they have limited effectiveness. A 2017 study in The British Medical Journal  of over 7,400 patients who had knee replacement surgery found the procedure often had minimal effects on quality of life and wasn’t worth the cost.

Arthroscopic surgery is less invasive than a total knee replacement, but studies also show it is often not effective. In 2017, an international panel of experts reviewed 25 studies involving nearly two million patients and concluded that arthroscopic surgery does not improve long term pain or function in patients with knee conditions such as osteoarthritis.

Because these conventional treatments often fail, there is growing interest in the use of stem cells to treat knee problems. The FDA, however, takes a dim view of autologous stem cells and released guidance in 2017 that requires the cells to undergo “minimal manipulation.”

The FDA recently sent letters to 20 stem cell manufacturers and clinics warning them they were violating FDA regulations. The agency says the science behind autologous cells is still in its early stages and they have not been proven to be safe and effective.

“There’s a false premise being asserted by some in the field that a product derived from a person’s own body and then manipulated and reinserted for another use different from the one it played in its original location is not subject to FDA regulation just because it originated from the person it was given back to,” then FDA commissioner Scott Gottlieb, MD, and Biologics Center Director Peter Marks, MD, said in a statement.

“We’ve seen too many cases of sponsors claiming that cells aren’t subject to FDA regulation just because the cells originated from the same patient to whom the eventual manufactured product is being given. And we’ve seen too many cases of companies making unsubstantiated claims that these treatments prevent, treat, cure or mitigate disease where the products have sometimes led to serious patient harm.”

Help Us Get Our Lives Back

By Andrea Giles, Guest Columnist

I am a 49-year old disabled nurse living in Wyoming. Since 2010, I have been diagnosed with ankylosing spondylitis, phantom limb pain and severe osteoarthritis with multiple major joint deformities.  My remaining knee is now bone on bone, requiring me to use a wheelchair. 

I lost my right leg and half of my pelvis after a total hip replacement due to the osteoarthritis, after which I developed a severe MRSA bacterial infection that resulted in the total hip disarticulation. I’ve had horrible phantom limb pain since the amputation. I also had 2 failed spinal fusions, leaving me with chronic back pain and nerve damage. Since 2010, I have had a total of 52 surgeries.

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From 2010 to 2016, I was treated with opioid medication by a pain management physician, with a stable, safe, effective and legal regimen. I followed all of the requirements, such as urine drug tests, pill counts, using the same pharmacy, etc.

Then, at an appointment in 2016, my physician told me that because of the CDC guidelines, he would no longer prescribe opioid medication to me. I was forced off my high dose (120MME) cold turkey. I was lucky, as I didn’t experience withdrawal symptoms other than the reappearance of severe, intractable pain.

I tried to use NSAIDS for the pain and developed a severe, life threatening reaction to them called Stevens-Johnson Syndrome. I came very close to death and was in intensive care for 6 weeks. Because of that, I will be unable to take NSAIDs for the rest of my life.

Because of the MRSA infection, no physician will perform any further surgeries or steroid injections on me because of the risk of activating another infection.

I have tried acupuncture, massage, chiropractic therapy, mirror therapy, physical therapy, water therapy, many different herbal and nutritional supplements, aromatherapy, music therapy, psychotherapy, hypnotherapy and mindfulness. All without relief of the severe, intractable pain.

When I was forced off opioids, I also lost my career as a very good ER nurse. I went from a functional member of society to a home-bound, miserable person who hurts too badly to keep my house clean like I always prided myself on. Many days I’m in too much pain to even shower or complete daily activities of living.

My husband and children have lost the wife and mother they were able to interact with, go places with, share activities with, everything. I have gained 50 pounds because the pain has left me unable to exercise.

After I stopped taking opioids, I developed hypertension.  Before, my blood pressure had never been higher than 130/80. Now I take medication for high blood pressure and it is still usually around 150/90.

I also developed heart arrhythmia and last year suffered 2 sudden cardiac arrests. I only survived because both times they were witnessed by my husband, who is also an ER nurse, so he immediately started CPR. The cardiologist could find no underlying causes and told me that the arrhythmia and cardiac arrests were probably due to longstanding, untreated severe pain.

There is no physician that I can find that will accept me as a chronic pain patient and my primary care doctor refuses to prescribe opioids anymore. I have literally tried every pain management physician in Wyoming and in Montana, which would have required a 6 to 7-hour drive for each appointment.

I, along with many other intractable pain patients, are working feverishly contacting our congressional representatives, federal government and civil rights groups, begging for help -- for anyone in a position of power to hear our cries of medical abandonment and neglect.

Our pleas mostly fall on deaf ears, as the government has convinced the media and the public that pain patients are all addicts and use opioids only to get high. They site false overdose statistics and refuse to acknowledge that while opioid prescriptions have declined -- causing devastating effects on the pain community -- the overdose rate continues to climb because the clear majority of overdoses are due to heroin, illicit fentanyl or polypharmacy with multiple drugs.

Many intractable pain patients are committing suicide because untreated pain takes away their quality of life and the will to live – something they had with legally prescribed and effective doses of opioid medication.

We are desperate. We don’t want to get high. We just want to make informed decisions with our physicians about our own healthcare, to regain access to opioid medication, and to get our lives back!

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Andrea Giles lives in Wyoming with her family.

Pain News Network invites other readers to share their stories with us. Send them to editor@painnewsnetwork.org.

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.

Positive Results for New Osteoarthritis Drug

By Pat Anson, Editor

Two pharmaceutical companies have announced positive results from a Phase 3 study of an experimental non-opioid pain reliever that has a history of safety concerns.

Teva and Regeneron are jointly developing fasinumab as a treatment for chronic pain from osteoarthritis of the knee and hip. The companies say patients treated for 16 weeks with fasinumab injections had significantly less pain and improved function compared to a placebo.

"We are encouraged by these data and look forward to advancing our pivotal Phase 3 fasinumab program in patients with osteoarthritis of the knee or hip, who currently have very limited therapeutic choices to treat their chronic pain, other than with non-steriodal anti-inflammatory drugs or opioids," said George Yancopoulos, MD, President and Chief Scientific Officer of Regeneron.

Fasinumab is a humanized antibody that targets nerve growth factor (NGF), a protein that increases in the body because of injury, inflammation or chronic pain. Fasinumab binds to NGF and inhibits pain signals from muscles, skin and organs from reaching the brain.

Teva and Regeneron say fasinumab was “generally well tolerated” in the Phase 3 study, with similar adverse events (AEs) as in previous trials. Treatment was discontinued due to AEs in 6 percent of the fasinumab patients, about the same as the placebo group. The companies plan to present further details at an upcoming medical conference.

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Regeneron recently halted high-dose trials of fasinumab because the risk of harm outweighed the benefits of the drug. There is some concern that NGF antibodies work too well and encourage osteoarthritis patients to become more active, which accelerates joint deterioration. No cases of joint damage were observed in the current study.

Regeneron and Teva are currently enrolling osteoarthritis patients in three additional Phase 3 clinical trials, including one assessing the long-term safety of fasinumab and two trials comparing fasinumab to standard pain therapies.

There is intense competition about drug companies to develop non-opioid pain relievers that don’t have the risk of addiction and overdose. Pfizer and Eli Lilly are jointly developing a similar NGF inhibitor called tanezumab, which was given fast track designation by the FDA in 2017 to speed its development.

Like fasinumab, there are safety concerns about tanezumab. The FDA ordered a partial halt to clinical studies of tanezumab in 2010 after Pfizer said a small number of osteoarthritis patients taking the drug needed joint replacements. Another safety issue arose in 2012 because the drug caused “adverse changes in the sympathetic nervous system of mature animals.”  Most clinical studies of tanezumab did not resume until 2015.

Grieving a Former Life

By Pamela Jessen, Guest Columnist

Once upon a time, there was a woman named Pamela. She was a strong, vibrant woman who worked as an operations administrative assistant for a company called FGL Sports, which operated a chain of sporting goods stores in Canada. Pamela took care of the administrative needs of the director and senior management team. 

Unknown to these people, Pamela lived with fibromyalgia and osteoarthritis. She did her job so well that she was able to keep these illnesses hidden for a long time, but they gradually started to get in the way of her work. Pamela eventually had to leave her job and go on permanent disability.

That was really devastating for Pamela because work was her life! She loved everything she did, from organizing training meetings and corporate functions to keeping her boss’s life on track. 

Once she was no longer working, a lot of negative feelings started to dwell up inside Pamela. She started feeling depressed, angry, sad and lonely. These were natural responses to having a chronic illness, but it was also frustrating to have to deal with them on top of not actually having a job to go to.

Pamela felt herself getting more depressed and sometimes it was easier to just stay in bed and sleep rather than get up and face life. She knew this wasn't good, but there really wasn't any reason to get up anymore.

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Well, of course, that woman was me. It was a difficult phase of my life, as work had always been my passion. I was an administrative specialist in retail support for most of my career and I loved what I did. Every day was a treat. Unfortunately, my body just couldn’t keep up with me. The pain and exhaustion that goes along with fibromyalgia and osteoarthritis took over my body and I had to surrender to it. There simply was no other choice. 

After some time, I took a chronic pain management course and started feeling better mentally. This course explored the various stages of grief we go through when you experience a job loss because of illness and disability, and I realized that was exactly what had happened to me. I had been grieving. 

There are five stages of grief: denial, anger, bargaining, depression and acceptance. The instructor asked us what we had to give up in our lives because of chronic illness. He had us make a list and to really think about what was on that list. Mine, of course, was my job and the volunteering that I loved to do. 

I knew going back to work wasn't going to happen again, but I was sure there must be a way I could use my volunteer skills on my terms. Then one day I noticed an advertisement in my local paper for an organization called Patient Voices Network in British Columbia and it looked perfect for me. The group was looking for volunteers who could be the voice of the patient when health care providers needed that voice in their engagements. I attended an orientation session and before I knew it, was attending my first assignment! I loved it from the start and have been an active participant ever since. 

Currently, I am the co-chair of the Oversight & Advisory Committee for Patient Voices Network. I also sit on the Clinical Resources Committee for the BC Emergency Physicians Network. 

It’s amazing how getting involved again in something you love can bring the grieving process full circle to acceptance. I realized that I had given up a lot because of fibromyalgia and osteoarthritis. But by accepting my new limitations, I actually gained a whole lot more.

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Pamela Jessen lives in Langford, British Columbia. She has a blog called There Is Always Hope, where she writes about living with invisible illness.

Pain News Network invites other readers to share their stories with us. Send them to editor@painnewsnetwork.org.

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.