Positive Findings for New Osteoarthritis Drug

By Pat Anson, Editor

Pfizer and Eli Lilly have announced positive findings in treating osteoarthritis pain with an experimental non-opioid drug that has a history of safety concerns.  

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

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In the 16-week clinical study, osteoarthritis patients who were given two injections of tanezumab had significant improvement in their pain, physical function and assessment of their symptoms compared to a placebo. Osteoarthritis is a joint disorder that leads to thinning of cartilage and progressive joint damage.

“There is a substantial need for innovative new treatment options for osteoarthritis, as many patients are unable to find relief with currently available medicines and continue to suffer,” Ken Verburg of Pfizer Global Product Development said in a statement.

“We are encouraged by these results, which speak to the potential of tanezumab as a non-opioid treatment option for pain reduction and improvement in physical function.”

Preliminary safety data showed that tanezumab was generally well tolerated, with about 1% of patients discontinuing treatment due to adverse events. Rapidly progressive osteoarthritis was observed in about 1.5% tanezumab-treated patients, but none in the placebo arm.

The U.S. Food and Drug Administration granted “fast track” designation to tanezumab last year to help speed its development as a new treatment for osteoarthritis and chronic low back pain.

Ironically, it was the FDA that slowed the development of NGF inhibitors in 2010 after Pfizer reported some osteoarthritis patients receiving tanezumab experienced worsening of their disease and 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.

“We look forward to continuing to advance tanezumab in our ongoing global Phase 3 development program, which includes six studies in approximately 7,000 patients with osteoarthritis, chronic low back pain and cancer pain,” said Christi Shaw, senior vice president of Eli Lilly. In studies to date, tanezumab has not demonstrated a risk of addiction, misuse or dependence.

Regeneron recently halted high-dose trials of fasinumab, another NGF inhibitor, 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.

Can a Junk Food Diet Cause Osteoarthritis?

By Steve Weakley

Does what’s in your gut influence the pain in your knees? New research on mice at the University of Rochester Medical School suggests that it might, but the results are far from conclusive.

Researchers fed one group of laboratory mice a high fat diet that included red meat and milkshakes, and another group of mice a healthier low-fat diet. Both groups of mice had their knees surgically damaged to mimic the effects of osteoarthritis -- “wear and tear” arthritis that is often associated with age, obesity or injury.

Twelve weeks of the high fat diet made the mice obese and diabetic and led to more seriously damaged joints. It also created an imbalance of harmful bacteria in their digestive tracts. 

One group of the fat mice were then given a supplement containing the prebiotic fiber oligofructose (also available as an over-the-counter probiotic).  The researchers said the supplement did not cause the mice to lose weight, but it did greatly improve their blood sugar levels and the balance of healthy bacteria in their gut.  More importantly, the study concludes, the mice that were given the supplement also had healthier joints than the control group.

The University of Rochester study concluded that prebiotics and the correction of gut bacteria might help protect against osteoarthritis caused by obesity. And one of the researchers, Dr. Robert Mooney, told Forbes that the study suggests osteoarthritis may be accelerated or even caused by inflammation.

"That reinforces the idea that osteoarthritis is another secondary complication of obesity--just like diabetes, heart disease, and stroke, which all have inflammation as part of their cause," said Mooney. "Perhaps, they all share a similar root, and the microbiome (digestive bacteria) might be that common root."

However a critique by Britain’s National Health Service (NHS) said that conclusion might be premature.

“It's presumptuous to conclude that an imbalance of gut bacteria could be directly linked to risk of osteoarthritis in humans from the results of a study in mice with artificially induced knee damage. As such, there's no compelling evidence that prebiotics would prevent or reverse osteoarthritis,” the NHS said.

“Aiming for a healthy weight through a good diet combined with physical activity is a better strategy for reducing the risk of osteoarthritis (as well as many other long-term conditions) than taking prebiotics to try to combat the effects of a poor diet. “

Osteoarthritis is a joint disorder that leads to progressive joint damage. It can affect any joint in the body but is most commonly felt in weight bearing joints such as the knees and hips. Nearly 40 percent of Americans over the age of 45 have some degree of knee osteoarthritis.

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Previous studies have also found a link between a high fat diet and osteoarthritis.  Australian researchers reported last year that a diet rich in animal fats, butter and palm oil weakens cartilage and produces osteoarthritis-like changes in the knee.

"We also found changes in the bone under the cartilage on a diet rich in saturated fat," said Professor Yin Xiao of Queensland University of Technology’s Institute of Health and Biomedical Innovation. "Our findings suggest that it's not wear and tear but diet that has a lot to do with the onset of osteoarthritis.”

The University of Rochester researchers hope to include humans in future studies on the effects of diet on osteoarthritis.

What the JAMA Opioid Study Didn’t Find

By Roger Chriss, Columnist

A recent opioid study published in the Journal Of the American Medical Association (JAMA)  evaluated pain management in patients with hip and knee osteoarthritis and low back pain.

The study by VA researcher Erin Krebs, MD, and colleagues found that “treatment with opioids was not superior to treatment with nonopioid medications for improving pain-related function over 12 months.”  

That finding was widely and erroneously reported in the news media as meaning that opioids are ineffective for all types of chronic pain.

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But the most fascinating result of the study – the one not being reported -- is what wasn’t found. The 108 people in the study who took opioids for a year did not develop signs of opioid misuse, abuse or addiction, and did not develop opioid-induced hyperalgesia – a heightened sensitivity to pain.

And no one died of an overdose.

This is significant because it runs counter to commonly held beliefs in the medical profession about the risks of prescription opioids. Here are a few recent examples:

“Opioids are very addictive and their effectiveness wanes as people habituate to the medication,” Carl Noe, MD, director of a pain clinic at the University of Texas Medical Center wrote in an op/ed in The Texas Tribune.

Don Teater, MD, a family physician in North Carolina, also believes that people on long-term opioid therapy experience dose escalation, which leads to hyperalgesia. “Opioids cause permanent brain changes,” Teater told USA Today.

Krebs herself has made similar comments. "Within a few weeks or months of taking an opioid on a daily basis, your body gets used to that level of opioid, and you need more and more to get the same level of effect,” she told NPR.

But the Krebs study didn’t see any of that happen.

Krebs and colleagues closely monitored the 108 people in the opioid arm of the study, using “multiple approaches to evaluate for potential misuse, including medical record surveillance for evidence of ‘doctor-shopping’ (seeking medication from multiple physicians), diversion, substance use disorder, or death.” They also had participants complete the “Addiction Behavior Checklist” and assessed their alcohol and drug use with surveys and screening tools.

What did Krebs find in the opioid group after 12 months of treatment?

“No deaths, ‘doctor-shopping,’ diversion, or opioid use disorder diagnoses were detected,” she reported. “There were no significant differences in adverse outcomes or potential misuse measures.”

Health-related quality of life and mental health in the opioid group did not significantly differ from the non-opioid group – and their anxiety levels actually improved.  

These are observational findings in the study. They were not a part of what Krebs and colleagues were specifically trying to measure. As the study notes: “This trial did not have sufficient statistical power to estimate rates of death, opioid use disorder, or other serious harms associated with prescribed opioids.”

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But they are valuable observations. They note what didn’t happen in the study. Over 100 people were put on opioid therapy for a year, and none of them showed any signs of dose escalation or opioid-induced hyperalgesia, or any evidence of opioid misuse, abuse or addiction.

Krebs told the Minneapolis Star Tribune that this “could reflect the fact that the study did not enroll patients with addiction histories, and because the VA provided close supervision to all participants during the yearlong study.”

In other words, Krebs and colleagues used an opioid prescribing protocol that achieved an admirable level of patient safety. Their approach is similar to what many pain management practices currently pursue and what the CDC and various state guidelines recommend: Risk assessment before initial prescribing and careful monitoring over time.

The Krebs study provides rare and detailed observations of what happens when people are put on long-term opioid therapy. A lot of what is claimed about dose escalation, opioid-induced hyperalgesia, and misuse or abuse didn't happen at all.

This outcome demonstrates that long-term opioid therapy can be safe and effective, and may be useful in treating other chronic conditions, from intractable neuropathies to painful genetic disorders. That’s worth reporting too, isn’t it?

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Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

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.

Is JAMA Opioid Study Based on Junk Science?

By Pat Anson, Editor

You may have read about a research study published this week in the Journal of the American Medical Association (JAMA), which compared the effectiveness of opioid and non-opioid medications in treating chronic pain. 

The yearlong study of 240 patients found that opioids were not superior to pain relievers like acetaminophen and ibuprofen in treating chronic back pain or hip and knee pain caused by osteoarthritis.  Pain improved for 41% of the patients who took opioids, compared to 54% in the non-opioid group.  

It’s an interesting study – one of the few to look at the effectiveness of any pain relievers long term – but some critics are questioning the study’s methodology and the alleged anti-opioid bias of its lead author, Erin Krebs, MD, a researcher for the Department of Veterans Affairs.

First let’s look at some of the news coverage the study is getting.

“Opioids Don’t Treat Chronic Pain Any Better Than Ibuprofen” reads the headline in Newsweek, an article that never mentions the JAMA study was limited to patients with back pain or osteoarthritis.

“Opioids Don’t Beat Other Medications for Chronic Pain” was the headline in NPR.com, while the Chicago Tribune went with “Opioids no better than common painkillers for treating chronic pain.”

The Tribune article included a quote from one of the co-authors of the CDC opioid guidelines. "The fact that opioids did worse is really pretty astounding," said Roger Chou, MD. "It calls into question our beliefs about the benefits of opioids."

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Notice the news coverage strongly suggests that opioids are ineffective for all types of chronic pain – not just back pain and osteoarthritis.  Patients living with chronic pain from arachnoiditis, trigeminal neuralgia or some other intractable pain condition would probably disagree about that. And they'd find the idea of taking ibuprofen laughable, if not infuriating. But no one asked for their opinion.

Also unmentioned is that opioids are usually not prescribed for osteoarthritis or simple back pain, which are often treated with NSAIDs and over-the-counter pain relievers.

So, what JAMA has published is a government funded study designed to look at a treatment (opioids) that most people with back pain and arthritis never actually get.

“You've been had by anti-opioid advocates disguising their advocacy as science.  Krebs is well known in professional circles for this kind of distorted advocacy junk science,” wrote patient advocate Red Lawhern, PhD, in a comment submitted to the Philadelphia Inquirer after it published a misleading headline of its own, “Prescription opioids fail rigorous new test for chronic pain.”

“I suggest that you retract your article.  In its present form, it is propaganda not fact,” said Lawhern, a co-founder of the Alliance for the Treatment of Intractable Pain (ATIP). “Opioids have never been the first-line medical treatment of choice in lower back pain or arthritis. That role is served by anti-inflammatory meds, some of them in the prescription cortico-steroid family.  NSAIDs have a role to play, recognizing that they are actively dangerous in many patients if taken at high doses for long periods.  Hundreds of people die every year of cardiac arrest or liver toxicity due to high-dose acetaminophen or ibuprofen.” 

Who is Erin Krebs?  

Dr. Krebs is an associate professor at the University of Minnesota Medical School and a prolific researcher at the VA Medical Center in Minneapolis.

She was also an original member of the “Core Expert Group” – an advisory panel that secretly drafted the CDC’s controversial opioid guidelines while getting a good deal of input from the anti-opioid activist group Physicians for Responsible Opioid Prescribing (PROP). The guidelines recommend that opioids not be prescribed for chronic pain.

Krebs also appeared in a lecture series on opioid prescribing that was funded by the Steve Rummler Hope Foundation, which coincidentally is the fiscal sponsor of PROP. 

Some of her previous opioid research has been controversial. In a study published last year in the Annals of Internal Medicine, Krebs reviewed 67 studies on the safety and effectiveness of opioid tapering. Most of the studies were of poor quality, but nevertheless Krebs came to the conclusion that pain levels and the quality of life of patients “may improve during and after opioid dose reduction.”

 ERIN KREBS, MD

ERIN KREBS, MD

“This review found insufficient evidence on adverse events related to opioid tapering, such as accidental overdose if patients resume use of high-dose opioids or switch to illicit opioid sources or onset of suicidality or other mental health symptoms,” wrote Krebs.

PROP founder Andrew Kolodny, MD, read the review and liked it, tweeting that “dangerously high doses should be reduced even if patient refuses.”

But forced opioid tapering is never a good idea, according to a top CDC official.

“Neither (Kreb’s) review nor CDC's guideline provides support for involuntary or precipitous tapering. Such practice could be associated with withdrawal symptoms, damage to the clinician–patient relationship, and patients obtaining opioids from other sources,” wrote Deborah Dowell, MD, a CDC Senior Medical Advisor, in an editorial also published in the Annals of Internal Medicine. 

As for Krebs’ contention that there is “insufficient evidence” of adverse events associated with opioid tapering, that notion may be put to rest next month when the VA releases a new study showing that tapering has led to a growing number of suicides by veterans.

In a summary of the findings, which will be presented at the Rx Drug Abuse & Heroin Summit, VA researchers report that “opioid discontinuation was not associated with overdose mortality, but was associated with increased suicide mortality.”  

Who and what should we believe in the neverending debate about opioids? PNN columnist Roger Chriss wrote about Krebs’ opioids vs. non-opioids study last year, when the initial reports of its findings came out. Roger said prescribing decisions are best left to physicians who know their patients’ medical conditions – not researchers, regulators or the news media.

“In reality, there is no ‘versus’ here. Opioids and NSAIDs are both valuable tools for chronic pain management. To pretend that one is inherently better than the other is to miss the essential point: Both work and should be available for use as medically appropriate,” Roger wrote. 

Osteoarthritis Drug Works No Better Than Placebo

By Pat Anson, Editor

Hydroxychloroquine (Plaquenil) is a medication commonly used to treat rheumatoid arthritis, lupus and other autoimmune diseases. It’s also being prescribed off-label to treat inflammation and pain caused by hand osteoarthritis, a joint condition that affects nearly a third of patients over the age of 70.

But in a new study published in the Annals of Internal Medicine, British researchers reported that hydroxychloroquine is no more effective than a placebo in relieving moderate to severe pain caused by hand osteoarthritis.

Researchers at the Leeds Institute of Rheumatic and Musculoskeletal Medicine and the Leeds Biomedical Research Centre randomly assigned 248 patients with radiographic hand osteoarthritis to either hydroxychloroquine (200 to 400 mg) or placebo for a year.

Most of the patients had symptoms of hand osteoarthritis for about 5 years, and their average pain level was 7 out of 10.

After 3, 6 and 12 months, there were no significant differences in treatment outcomes between the hydroxychloroquine and placebo groups.

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“We found that HCQ (hydroxychloroquine) was not a more effective analgesic than placebo when added to usual care in persons with moderate to severe hand osteoarthritis,” researchers reported. “Background analgesic use did not differ between groups, and baseline inflammation and structural damage did not affect response to HCQ. The study therefore presents no evidence that HCQ should be considered within the management plan of patients with hand osteoarthritis.”

Two doctors who reviewed the study say more research is needed to find drugs that can treat the inflammation caused by hand osteoarthritis, a condition for which there are no effective therapies.

“The negative findings in this carefully done trial beg the question of what went awry. Did HCQ fail to reduce inflammation, or did reduced inflammation not translate to pain relief?” wrote Elena Losina, PhD, and Jefferey Katz, MD in an editorial.

“Although HCQ is safe, it is also a weak anti-inflammatory agent seldom used in contemporary practice as a solo disease-modifying therapy for rheumatoid arthritis and other inflammatory conditions. Further therapeutic studies of the effects of anti-inflammatory therapy on nodal hand osteoarthritis will need to use more potent agents or compounds developed to more specifically target the inflammatory pathways documented in this condition.”

Why Does Menopause Worsen Rheumatoid Arthritis?

By Pat Anson, Editor

A large new study is confirming what many women with rheumatoid arthritis (RA) already know – menopause and hormonal changes can significantly worsen their pain and other symptoms. But it's not clear why that happens.

Researchers at the University of Nebraska Medical Center enrolled over 8,000 women with RA – both young and old -- in their observational study. They found that post-menopausal women with RA had a significant increase in the level and rate of functional physical decline. Menopause was also associated with a worsening progression of the disease.

RA is a chronic and disabling autoimmune disease in which the body’s own defenses attack joint tissues, causing pain, inflammation and joint erosion. Women experience RA at a rate three times greater than men, have more severe symptoms and increased disability.

Previous studies have shown that women with RA experience changes in their disease during reproductive and hormonal changes. During pregnancy, women are less likely to develop RA, yet the disease is more likely to progress and flare during the post-partum period. Similarly, women who experience early menopause are more likely to develop RA compared to those who experience normal or late menopause.

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Hormone levels of estrogen increase during pregnancy and decline during menopause – but the association with RA is not fully understood.

"Further study is needed as to why women with rheumatoid arthritis are suffering a greater decline in function after menopause," said the study's lead author, Elizabeth Mollard, PhD, an assistant professor in the College of Nursing at the University of Nebraska Medical Center.

"Not only is this decline causing suffering for women, it is costly to both individuals and the healthcare system as a whole. Research is specifically needed on the mechanism connecting these variables with the eventual goal of identifying interventions that can maintain or improve function in postmenopausal women with rheumatoid arthritis."

The study is published in the journal Rheumatology.

RA affects about 1.3 million Americans and about one percent of the global population. Until the late 1990s, one in three RA patients were permanently disabled within five years of disease onset.

Although there are still 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. Those treatments are expensive, with some biologic therapies costing $25,000 a year.

Stem Cells: Signs of Progress in a Rigged Game

By A. Rahman Ford, Columnist

The Wall Street Journal recently published an article on the use of stem cell therapies for knee problems, including arthritis.  Overall, the perspective of the piece was positive and it has several laudable aspects.  Physicians from large academic institutions, such as Harvard University and Stanford University, were interviewed to provide their opinions on the use of autologous stem cells derived from a patient’s own fat or bone marrow for certain painful orthopedic indications. 

The article rightly acknowledges the high patient demand for these autologous therapies. It also mentions how the U.S. lags behind other countries in offering them and the disturbing fact that this therapy is not covered by medical insurance.  The doctors who were interviewed also discussed how conventional approaches to osteoarthritis in knees – meniscus surgery, microfracture surgery, etc. – often fail to demonstrate long-term benefit.  These doctors, along with many others around the world, recognize that we need new therapies for orthopedic conditions.

Any positive portrayal of the clinical uses of stem cells should be welcomed. The unfortunate truth is that many potential patients are scared off by publications that focus their reporting on the alleged malfeasance of a few bad-actor stem cell clinics.  These same publications often neglect to cover the countless stem cell success stories from clinics in the U.S. and abroad. 

A focus on these promising results may help allay those fears and convince some of those fearful patients that stem cells are, in fact, a viable medical option for their chronic orthopedic pain. 

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Less fear can lead to self-education and increased awareness of the safety and potential of stem cells.  Patients may even try stem cell therapy and become advocates.  In this sense, the WSJ piece is good public relations for stem cell therapies overall.

However, there is an unsettling undertone in the WSJ piece and media coverage in general of stem cells, which places too much emphasis on the opinions of clinicians from certain large institutions.  That diminishes the value of work being done in smaller stem cell clinics, which have been safely and effectively treating patients with orthopedic conditions for years. 

The unintended implication is that Harvard and Stanford physicians’ assessments are more legitimate because of the perceived prestige of their employers, and because they follow the guidelines that the FDA set forth for pursuing such treatments.  Of course, these institutions have millions of dollars in capital that it takes to conduct clinical studies and comply with these guidelines, while smaller clinics often do not.  We must take care to avoid creating or reinforcing illegitimate hierarchies that give some physicians more scientific authority than others, based solely on money, perceived prestige, or the ability to adhere to an unfair set of rules.

The sad truth is that the stem cell game is rigged.  The FDA’s rules regarding the use of autologous stem cell therapies favor those with more financial resources because they can afford expensive clinical trials.  Medical innovation cannot be strictly the domain of wealthy institutions with the finances to play on a tilted field.  The FDA’s “minimal manipulation” and “homologous use” regulatory standards for using stem cells are unduly burdensome and need to be relaxed for autologous stem cell uses. 

Recently, the FDA issued a warning letter to American Cryostem, a company involved in the manufacture of adipose stem cell products derived from a patient’s body fat.  In addition to manufacturing violations, the company was accused of violating the FDA’s “minimal manipulation” and “homologous use” standards. 

Setting the merits of the case aside, it is emblematic of the FDA’s crackdown on clinics that are much smaller than Harvard and Stanford, but which have been relieving patients’ pain with autologous therapies for years.  Their scientific contributions must not be subordinated or dismissed as illegitimate or inconsequential.

Stories of how stem cells are entering mainstream medicine can help us realize the goal of available, affordable stem cell therapy for all Americans.  However, valorization of those institutions with the means to “play within the rules” must not come at the expense of sounding the alarm that the rules themselves are patently unfair.

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A. Rahman Ford, PhD, is a lawyer and research professional. He is a graduate of Rutgers University and the Howard University School of Law, where he served as Editor-in-Chief of the Howard Law Journal. He earned his PhD at the University of Pennsylvania.

Rahman lives with chronic inflammation in his digestive tract and is unable to eat solid food. He has received stem cell treatment in China.  

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.

Legal Battles Brew Over High Cost of Arthritis Drugs

By Julie Appleby, Kaiser Health News

Early last winter, Pfizer launched its new rheumatoid arthritis treatment, Inflectra, pricing it 15 percent below the $4,000-a-dose wholesale price of Remicade, the drug for which it is a close copy.

Pfizer figured its lower price would attract cost-conscious insurers.

A year later, though, its drug has barely scratched the market and Pfizer has filed an antitrust suit against its rivals, alleging they are thwarting lower-priced competition through “exclusionary contracts” and rebates.

The outcome of the case — filed in September in U.S. District Court against Johnson & Johnson, the maker of Remicade, and Janssen Biotech — could affect the future of biosimilars, a new class of drugs. Some policy experts say these near-copies of biologics are key to slowing spending on complex and expensive specialty medications like those used to treat rheumatoid arthritis.

At the heart of the case are rebates, which are discounts off the wholesale price of drugs.

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Manufacturers offer them to help keep their products on insurers’ lists of covered drugs. The money mainly goes back to insurers and pharmacy benefit managers, who say the rebates help reduce health care spending.

But Pfizer alleges that those rebates are being used to thwart biosimilars’ entry into the marketplace.

“This is the first antitrust case we’ve seen like this around biosimilars,” said Michael Carrier, a Rutgers Law School professor “Pfizer is claiming that one form of anti-competitive behavior involves withholding rebates from insurers.”

Biosimilars are costly to produce, so they are not likely to trigger the same sharp pricing drop triggered by generics. Still, their manufacturers say they could bring consumers some relief to rival biologics’ high price tags.

Pfizer’s Inflectra is one of the first biosimilars to hit the market since Congress passed legislation in 2010 to pave the way.

According to Pfizer, weeks after Inflectra gained Food and Drug Admininstration approval, J&J moved to stake out its biologic turf.

J&J began requiring insurers and PBMs to sign “exclusionary contracts … designed to block both insurers from reimbursing and hospitals and clinics from purchasing Inflectra or other biosimilars of Remicade despite their lower pricing,” alleges the case filed in federal district court in Philadelphia.

If insurers don’t agree to the J&J contracts, the loss of rebates could “for some insurers, run into the tens of millions of dollars annually,” the Pfizer case alleges.

Even with its lower price, Pfizer faced an uphill battle to win market share.

Remicade is the fifth-biggest-selling drug by revenue in the U.S., reaping more than $4.8 billion in 2016 for makers J&J and Janssen, the suit said. Often, patients are reluctant to switch once they are established on an RA drug that is working for them.

Still, Pfizer thought it would pick up newly diagnosed patients and gain ground that way. But its lawsuit says the drug accounted for only about 4 percent of total sales, with Remicade getting the rest, by early September.

“We stand by our contracts,” said J&J and Janssen Biotech in a written statement. The firms also defend rebates as “competition that is doing what competition is meant to do: driving deeper discounts that will lead to overall lower costs.”

Yet the price of Remicade has not fallen, the Pfizer case says.

Since approval of Inflectra, J&J has raised the list price of Remicade by close to 9 percent, the lawsuit alleges. As of September, Remicade’s average sales price –after discounts and rebates — is more than 10 percent higher than Inflectra.

“This case is a big deal, because it has the potential to bring to light some of the anti-competitive contracting practices at work to keep … prices extremely high,” said Jaime King, a professor at University of California-Hastings College of the Law.

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

Rising Cost of Arthritis Drugs Defies Economics

By Julie Appleby, Kaiser Health News

Renda Bower knows well the cost of drugs to treat rheumatoid arthritis – her husband, son and daughter all have the painful, disabling autoimmune disease. And the family’s finances revolve around paying for them.

Even with insurance, Bower’s family last year faced $600 a month in copayments for the drug, plus additional payments on another $16,000 in medical bills racked up in 2016 when a former insurer refused to cover all the doses her 9-year-old daughter needed.

Bowers, of Warsaw, Ind., said her family tries to keep up with prices by cutting back on her children’s sports and extracurriculars and skipping family vacations. She also works as a part-time teacher.

But financially, it’s hard. “The cost should not be this high,” she said.

Wholesale prices for Humira and Enbrel, the two most commonly used treatments for rheumatoid arthritis, known as RA, increased more than 70 percent in the past three years.

Since the first RA drug came to market a decade ago, nearly a dozen have been added. If basic economics prevailed, RA treatments and patients would have benefited from competition.

But, because of industry price-setting practices, legal challenges and marketing tactics, they haven’t. The first RA drug cost $10,000 a year. It now lists for more than $40,000 — even as alternatives have entered the U.S. market.

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“Competition generally doesn’t work to lower prices in branded specialty drugs,” said Peter Bach, director of Memorial Sloan Kettering’s Center for Health Policy and Outcomes.

Humira is the world’s No. 1 prescription drug by revenue. AbbVie manufactures and markets the drug and is on track to reach revenue from the product of $17 billion this year.

Other RA treatments are also among the top 10 drugs by revenue sold in the U.S. Enbrel, made by Amgen, ranks as No. 3. Remicade, by Janssen Biotech, is fifth. Some RA medications are approved for other conditions, including psoriatic arthritis, Crohn’s disease and psoriasis.

About 1.5 million Americans have rheumatoid arthritis. The Bowers found some relief this year but not because prices dropped. Rather, Renda’s husband left his job at an engineering firm to work as a machinist at a medical device company that has an insurance plan with lower copayments. Her daughter was accepted into a clinical trial at Cincinnati Children’s Hospital. The trial covers the drug’s cost but not the associated expense of weekly travel, among other things.

Middlemen Benefit As Wholesale Price Rises

The complicated pharmaceutical supply chain in the United States means middlemen — such as pharmacy benefit managers (PBM) and, in some cases, hospitals and doctors’ offices — can gain financially by choosing more expensive drugs. That’s because PBMs usually get a rebate from the drugmakers on top of whatever profit they get from selling or administering the drug.

Those rebates often are based on a percentage of the list, or wholesale, price. So, the middlemen who get the rebates take in more money when drugmakers raise those sticker prices.

But who pockets the rebates? PBM firms, which oversee drug benefits for millions of Americans, say they share all or part of them with the insurers or employers who hire them. In some cases, the rebates go directly to specialty pharmacies, medical clinics or physicians dispensing the treatments.

The rebates rarely end up directly in patients’ pockets.

Those rebates affect the market in another way: They can make it harder for some companies to offer new treatments or they can thwart less costly rival products.

“We could give [our new drug] away for free and … it would still be more economically advantageous” for insurers and PBMs to send patients to Humira first, said Andreas Kuznik, a senior director at Regeneron Pharmaceuticals, at a conference examining the cost and value of RA treatments.

Thomas Amoroso, medical director for medical policy at Tufts Health Plan, said at the same March conference that he has found drug industry sales representatives to be persistent in tracking how their drugs are positioned on plan formularies.

If insurers decide to add a new, lower-cost drug as the preferred alternative, “our Humira rep would be knocking on our door next week and saying, ‘Hey, that rebate we gave you? We’re taking it back,’” Amoroso said.

The roundtable at which they spoke was part of an assessment of RA drug pricing convened by the Institute for Clinical and Economic Review, a nonprofit that evaluates the value of medical tests and treatments for insurers and other clients.

PBMs won’t disclose the rebates they provide to clients, but studies provide a clue. It’s a huge amount of money.

The Berkeley Research Group, a consulting firm that advises major employers, said that rebates and other discounts paid to insurers, PBMs and the U.S. government for brand-name drugs grew from $67 billion in 2013 to $106 billion in 2015.

Most RA drugs are a complex type of medication, called biologics, which are made in living organisms. Nearly identical copies of biologics are called biosimilars. They hold the promise of lower prices, just as generic drugs did for less complex medications.

While several biosimilar RA treatments have won Food and Drug Administration approval, including replicas of Humira, Enbrel and Remicade, most are tied up in court battles over patents. And those biosimilars that have made it to market are now the subject of new areas of legal challenge.

In mid-September, Pfizer filed what will be a closely watched antitrust lawsuit against Johnson & Johnson. The case alleges that J&J is using exclusionary contracts and the threat of withdrawing rebates to protect Remicade from Pfizer’s lower-priced biosimilar, Inflectra, which hit the market last winter.

J&J defends its contracts, saying they are “driving deeper discounts that will lead to overall lower costs.”

Arguments For And Against Rebates

Rebates are under increasing scrutiny, amid growing alarm about soaring prescription drug prices in the United States. But the Pharmaceutical Care Management Association, the PBM industry’s trade lobby, said that complaints that rebates help fuel higher prices are unfounded.

These rebates, the lobby says, help save the health system millions of dollars by shifting dollars back to insurers or other clients, who can then use them to lower future premium increases. This year, it commissioned a study that found no correlation between rebates and the rising list prices of the top 200 brand-name drugs, suggesting higher rebates didn’t necessarily drive higher prices.

“The rebate system exists because [insurers, employers and other clients] want discounts,” said Steve Miller, chief medical officer for Express Scripts, one of the nation’s three largest PBMs.

Express Scripts offers clients an option to give patients the discount directly, but most choose not to, he said.

“While individual patients would get the benefit, everyone else’s premiums would go up [because the rebate savings would not flow back to the insurer],” Miller said. “Changing where the rebate goes doesn’t lower the price of the drug.”

But rebates play a role in what some patients pay at the pharmacy counter.

It stems from a simple calculation: whether a patient’s insurance copayment is based on a percentage of the drug’s wholesale price or the drug’s price after rebates are given to the middlemen.

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Heidi Barrett , a mother of five from Everett, Wash., faces a 10 percent copay whenever she or one of her four children who have RA, all of whom have been on medication for years, go for their monthly infusion of Remicade.

Although Barrett is shielded from much of the cost because she has good employer-based insurance through her husband’s job, the question of whether her monthly copayments are based on the wholesale price or the after-rebate price rankles her.

“I have asked that question of the insurance company. I’ve asked that of our union,” said Barrett, 47, a paralegal who isn’t working because she spends so much time on her children’s treatments. “I never got any answers back.”

Based on data analyzed by Bach’s group at Sloan Kettering to determine the cost of 100 milligrams of Remicade, it appears she is paying based on the pre-rebate price.

Here’s how that works: Barrett’s 18-year-old son recently received a 600 mg dose that required a copay of $655. That is close to 10 percent of Remicade’s average U.S. wholesale price for that dose of $6,450, the Bach analysis showed.

Barrett is not benefiting from the rebate that middlemen receive.

Rebates and discounts, however, drive down the price for pharmacy benefit managers, hospitals or doctors.

According to the analysis, the average net cost of a 600 mg dose is $4,140, once all discounts are calculated. If Barrett could use that base price as her copay, she would save more than $240. For her entire family — all her children and Barrett take similar doses — that equals a savings of $1,000 a month.

With her current insurance, Barrett quickly meets a yearly $12,900 deductible. She considers herself lucky that her insurer then picks up the drug’s full cost. But the experience has changed her motherly advice to her children, who are 10, 18, 19 and 25, about what to hope for in life.

“I tell them, you can be anything you want when you go grow up. But you need to go to a company with good health insurance, even before you look at the salary or whether you’ll be happy there, your first priority is health insurance,” Barrett said. “It’s an insane world we live in.”

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

9 Holistic Approaches to Relieve Joint Pain

By Nicole Noel, Guest Columnist

Whatever your ailment may be, holistic medicine has an answer.

A therapeutic method that dates back to early civilizations, holistic medicine takes into account the mind, body, emotions and spirit -- with the aim of helping patients achieve or restore proper balance in life and prevent or heal a range of conditions, including musculoskeletal pain. Holistic treatments offer a ray of hope for many patients suffering from arthritis, osteoporosis, fibromyalgia and other conditions that cause joint pain.

Not all alternative medicine is created equal, and some natural healing methods will produce better and quicker results. If you want to treat arthritis and other joint aches with holistic treatments, here are a few natural pain relievers you can try.

1. Tai Chi

A low-impact activity that can increase range of motion and strengthen joints and surrounding muscle tissue, tai chi is an ancient physical and spiritual practice that can help arthritis patients soldier through their pain.

According to a 2013 study, tai chi can relieve pain, stiffness, and other side-effects of osteoarthritis. In addition to pain relief, tai chi can help improve range of motion and alleviate joint pain for people living with fibromyalgia and rheumatoid arthritis.

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2. Yoga

Another ancient technique which promotes natural healing, yoga is perfect for individuals suffering from lower back and joint pain. Gentle stretches and poses opening the joints can help prevent and alleviate chronic soreness in the shoulders, hips, and knees.

A form of yoga called mudras utilizes a series of hand gestures to increase energy, and improve mood and concentration.

3. Massage

An invigorating massage with warm essential oil can help many conditions, and joint pain is one of them.

By enhancing blood flow, relaxing the muscle tissue and soothing inflammation, a well-timed massage can ease joint stiffness and increase range of motion in individuals suffering from arthritis, fibromyalgia, and osteoporosis.

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4. Acupuncture

A 2013 review of medical studies has shown that acupuncture can help relieve musculoskeletal pain caused by fibromyalgia. By activating the body’s natural pain relief system and stimulating the nerves, muscles and connective tissue, acupuncture can relieve joint aches for people who are resistant to other holistic pain relief techniques.

A 2010 study found that acupuncture can also be a beneficial for peripheral joint osteoarthritis.

5. Diet Changes

An apple a day may or may not keep the doctor away, but a custom-tailored diet can help you with joint pain. Nutritional tweaks can begin with increased intake of chondroitin sulfate, glucosamine, and Omega 3 fatty acids, which can reduce joint pain in arthritis and osteoporosis patients.

To ease joint problems, your pantry should be stocked with foods that promote healing and reduce inflammation, such as onions, carrots, and flaxseed. Herbs and spices such as turmeric (curcumin) and cayenne pepper can also help with pain relief.

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6. Aromatherapy

If you think pain relief can’t smell good, you’re mistaken. Studies have shown that peppermint and eucalyptus oil can reduce swelling, pain and discomfort in patients with inflamed joints. For joint soreness and stiffness caused by arthritis, aromatherapy experts recommend regular application of myrrh, turmeric, orange, or frankincense oil to ease inflammation and pain, and to increase range of motion.

You can also combine aromatherapy with heat and cold treatments.  Be sure to keep the tender joints elevated during treatment to reduce swelling.

7. Spa Treatments

Few things can beat the appeal of a full-scale spa experience. If you’re suffering from knee, hip, shoulder or elbow pain and other holistic methods haven’t helped, try balneotherapy, which combines aqua massage with deep soaks in heated mineral water and medicinal mud baths.

One study found that balneotherapy significantly reduced knee and back pain in older adults.

8. Aquatic Sports

If you don’t want to immerse yourself in mud, you can supplement your holistic pain therapy with water aerobics, swimming, aqua jogging or aqua spinning. According to a 2014 study, water exercises can ease pain and improve joint function for osteoarthritis patients.

Additionally, a 2015 study found that aquatic circuit training can help relieve knee pain in cases of progressed osteoarthritis.

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9. Capsaicin cream

Another natural treatment for joint pain and stiffness is homemade capsaicin cream, which can help reduce swelling and increase range of motion. To stay on the safe side, you should be careful when handling hot peppers when preparing the cream, and avoid using it on sensitive and damaged skin.

As our bodies age, joint pain can become a chronic. If you don’t want to take your chances with conventional pharmaceuticals, you can always turn to holistic medicine for answers and help. When musculoskeletal pain hits home, one or more of these holistic treatments can help.

Nicole Noel is a lifestyle blogger who is passionate about yoga and healthy living. She enjoys sharing her experiences and ideas on how to lead a happy and healthy life. If you want to read more from Nicole, you can find her on Twitter and Facebook.

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.

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Study Finds Rain Not Linked to Joint Pain

By Pat Anson, Editor

The debate over weather’s influence on pain is heating up again, with the release of a new study that showed warmer temperatures -- not rainy conditions -- are associated with an increase in online searches about joint pain.

The apparent increase in knee and hip pain may be due to increased outdoor physical activity, according to researchers who reported their findings in PLOS ONE.

Investigators used Google Trends to analyze how often people used Google’s search engine to look up words and phrases associated with hip pain, knee pain and arthritis. Then they compared the results with local weather conditions at 45 U.S. cities. The weather data included temperature, precipitation, relative humidity and barometric pressure - conditions previously associated with increases in musculoskeletal pain.

Researchers found that as temperatures rose, Google searches about knee and hip pain rose steadily, too. But knee-pain searches peaked at 73 degrees Fahrenheit and became less frequent at higher temperatures. And searches for hip-pain peaked at 83 degrees and then tailed off.

Surprisingly, rain actually dampened search volumes for both knee and hip pain.

"We were surprised by how consistent the results were throughout the range of temperatures in cities across the country," said Scott Telfer, a researcher in orthopedics and sports medicine at the University of Washington School of Medicine.

Searches about arthritis, which was the study's main impetus, had no correlation with weather conditions.

"You hear people with arthritis say they can tell when the weather is changing," he said. "But with past studies there's only been vague associations, nothing very concrete, and our findings align with those."

What do the findings mean?

Because knee and hip-pain searches increased until it grew warm, and rainy days tended to slightly reduce searches for hip and knee pain, the researchers speculate that changes in outdoor physical activity may be primarily responsible for those searches.

"What we think is much more likely explanation is the fact that people are more active on nice days, so more prone to have overuse and acute injuries from that and to search online for relevant information,” Telfer said, adding that web searches are often the first response people have to health symptoms.

Researchers in Australia recently reported that cold, rainy weather has no impact on symptoms associated with back pain or osteoarthritis. Warmer temperatures did slightly increase the chances of lower back pain, but the amount of the increase was not considered clinically important. 

A previous study on back pain and weather by The George Institute for Global Health had similar findings, but received widespread criticism from the public, a sign of just how certain many people are that weather affects how much pain they feel.

“I know it is going to rain or have a thunderstorm before the weather person announces it on the news,” says Denee Hand, who suffers back pain from arachnoiditis, a chronic inflammation of the spinal membrane. She says the pain spreads down to her toes when the weather changes. 

“It is like my nervous system and muscles react to the coming weather and finally I get pain that feels like the tops of both my feet are being crushed,” she said in an email to PNN. “I have compression of the spinal cord with nerve damage to my nerves from the scar tissue and when the weather changes the scar tissue presses down against the damaged nerves.”

Researchers at the University of Manchester recently ended a study involving thousands of people who used smartphone apps to report their pain levels, giving investigators the ability to compare the pain data with real-time local weather. Researchers are now analyzing the database compiled over the last 15 months and will release their results next spring.

Insurance Claims Climb for Lyme Disease

By Pat Anson, Editor

Private insurance claims with a diagnosis of Lyme disease have soared in the U.S. over the past decade, according to a new report by FAIR Health, a nonprofit that tracks healthcare costs and insurance trends.

Lyme disease is a bacterial illness spread by ticks. It can also lead to other chronic pain conditions such as joint and back pain, chronic fatigue, fibromyalgia and neuropathy.

Fair Health analyzed a database of 23 billion private insurance claims from 2007 to 2016, and found that claims with a diagnosis of Lyme disease increased by 185 percent in rural areas and 40 percent in urban areas.

A recent CDC study also found the number of Lyme disease cases increasing, with nearly 40,000 confirmed and probable cases in 2015.

"Lyme disease is growing as a public health concern,” said FAIR Health President Robin Gelburd

Although Lyme disease historically has been concentrated in the Northeast and upper Midwest, the FAIR Health study suggests that it is spreading geographically. In 2007, insurance claims with diagnoses of Lyme disease were highest in New Jersey, Rhode Island, Connecticut, Massachusetts and New York.

By 2016, the top states were Rhode Island, New Jersey, Connecticut, North Carolina and New York -- with the emergence of North Carolina suggesting significant expansion to a new region.

Summer is the peak season for Lyme disease, with insurance claims more common in rural than in urban settings, according to the FAIR Health report. In the winter and early spring (December through April), claims involving Lyme disease were reported more often in urban than rural settings.

Age is also a differing factor in rural and urban environments. In rural settings, claims with Lyme disease diagnoses were more common for middle-aged and older people. Patients aged 41 years and older accounted for nearly two-thirds of the rural diagnoses. In urban populations, younger individuals with Lyme disease accounted for a higher percentage of claims.

Lyme disease is usually treated with antibiotics, but some patients experience complications that lead to Lyme disease syndrome (PTLDS), with long-term symptoms such as fatigue, muscle and joint pain and cognitive issues. Autoimmune diseases have also been associated with chronic Lyme disease.

Left untreated, Lyme disease can lead to serious chronic conditions, as Sarah Elizabeth Hirschle shared with us recently.

For patients with a Lyme disease diagnosis, FAIR Health reported the most common subsequent diagnoses were:

  • Joint pain (dorsalgia, low back pain, hip and knee pain)
  • Chronic fatigue  
  • Soft tissue disorders (myalgia, neuralgia, fibromyalgia)
  • Hypothyroidism
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Early symptoms of Lyme disease include fever, chills, headaches, fatigue, muscle and joint aches, and swollen lymph nodes. A delayed rash often appears at the site of the tick bite. The rash grows in size and sometimes resembles a bulls-eye.

To see some tips from the CDC on how to avoid tick bites, click here.