FDA Approves Generic Gilenya for Treatment of MS

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration has approved the first generic versions of Gilenya (fingolimod) for the treatment of relapsing forms of multiple sclerosis (MS). That’s welcome news for patients who have long struggled with the exorbitant cost of many MS medications.

A 30-day supply of Gilenya 0.5mg capsules currently costs about $8,130, according to Healthcare Bluebook, or about $97,560 a year.

“Approving safe and effective generics so patients have more treatment options continues to be a priority for the FDA,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a statement. “Having access to affordable treatments is important for patients with conditions that require ongoing care. The FDA has a longstanding commitment to increasing patient access to lower-cost, high-quality generic medicines.”

The FDA approved generic fingolimod applications from HEC Pharm Co. Limited, Biocon Limited and Sun Pharmaceutical Industries Limited.

Until now, Novartis held the exclusive patent rights to fingolimod, which is sold under the brand name Gilenya. Nearly 300,000 people worldwide have taken Gilenya since it was approved by the FDA in 2010, according to Novartis.

MS is a chronic and progressive disease that attacks the body’s central nervous system, causing numbness in the limbs, difficulty walking, paralysis, loss of vision, fatigue and pain. For most people with MS, there are periods of remission followed by relapses or flareups as the disease progresses. Gilenya is a widely used treatment for relapsing MS.

Generic formulations are often significantly cheaper than brand name drugs. In July, the FDA approved the first generic forms of Lyrica. Today a two-month supply of Lyrica costs about $472, while the same amount of generic pregabalin costs just $21.

Maximizing Profit

Criticism about the high cost of branded MS drugs is growing. Last month when the FDA approved a new MS medication called Vumerity, drug maker Biogen set its wholesale price at $88,000 a year. That brought a rare rebuke from the National Multiple Sclerosis Society, which released a statement that accused Biogen of price gouging.

It can take years for a new drug to get FDA approval and the pharmaceutical industry has long claimed that it needs to set prices high to recover the cost of research, clinical studies and drug development.

That claim is discounted in a recent article published in the journal Neurology, in which researchers asked four drug industry executives about the high cost of MS drugs. The executives were given anonymity to encourage them to speak freely.  

"I would say the rationales for the price increases are purely what can maximize profit," one executive said. "There's no other rationale for it.”

In setting the price for a new drug, executives said they primarily look at what their competitors are charging for similar medications. Companies fear that undercutting competitors with a lower price would undermine the attractiveness of their product.

"We can't come in at less," one of the executives said. "That would mean we're less effective, we think less of our product, so we have to go more."

The problem is unique to the United States, the only developed country that doesn’t have a universal healthcare system that regulates prices.

"And it is only in the United States, really, that you can take price increases. You can't do it in the rest of the world. In the rest of the world, prices decline with duration in the marketplace," another executive said.

Researchers say their study provides new insight into the economics behind pharmaceutical pricing.

"The frank information provided by these executives pulls back the curtain of secrecy on how drug price decisions are made," said co-author Dennis Bourdette, MD, chair of neurology at the Oregon Health & Science University School of Medicine. "We see that it is indeed the race to make more money that is driving up drug prices and nothing more."

In the meantime, MS patients like Jennifer Hochgesang struggle to make their co-payments and deductibles. She gets injections of glatiramer acetate, a generic version of Copaxone.

“It costs over $5,500 a month. When you add my migraine medication and other medications, it adds up to over $13,000 a month. I reach catastrophic level by March in my insurance and that’s the only way I can pay for it,” Hochgesang said. “It doesn’t cost that much in Europe though and it shouldn’t cost that much here.

“It seems sick to me that companies use a drug like this to profit highly from, when people can’t reasonably afford five thousand dollars a month. I believe an MS drug should be accessible to anyone. Otherwise we are only creating medicine for the rich and those able to get insurance or be on disability, leaving the rest out in the cold. That just isn’t right.” 

Biogen Accused of Price Gouging for New MS Drug

By Pat Anson, PNN Editor

FDA approval of a new multiple sclerosis (MS) drug has resulted in a big payoff for one company and sharp criticism from a patient advocacy group.

Last month the FDA approved Vumerity (diroximel fumarate) for the treatment of relapsing-remitting and secondary-progressive MS, as well as management of clinically isolated syndrome (CIS), neurologic symptoms that can be an early sign of MS — a chronic and progressive disease that attacks the body’s central nervous system.

Vumerity was jointly developed by Biogen and Alkermes. Under the terms of their operating agreement, FDA approval triggered a clause in which Biogen paid Alkermes $150 million for the worldwide commercial rights to Vulmerity, along with a share of future royalties.

Biogen said it would account for the Alkermes payment by amortizing its cost “over the expected useful life of the product.” It then announced the price of Vumerity – at a wholesale acquisition cost (WAC) in the U.S. of $88,000 per year. Biogen claimed that was “the lowest annual WAC price for oral MS disease-modifying therapies.”

MS drugs are notoriously expensive, but the $88,000 price tag for Vumerity brought a rare rebuke from the National Multiple Sclerosis Society, which released a statement that basically accused Biogen of price gouging.

“Vumerity is an efficacious and tolerable treatment option for people with relapsing MS, but being priced only $500 lower than the least expensive oral disease modifying treatment, does not show the commitment to affordable access that we had hoped,” said Bari Talente, executive vice president of advocacy for the National MS Society.

“We know that high wholesale acquisition cost (WAC) prices for MS disease modifying treatments put a heavy burden on people with MS. Too many are forced to take on high out-of-pocket costs, navigate through complex systems, and face varied and unpredictable decisions by public and private payers and pharmacy benefit managers.”

The statement points out Biogen has steadily escalated the price of another MS product, Tecfidera, by $40,000 since its launch in 2013. A year’s worth of treatment with Tecfidera now costs nearly $95,000.

“We urge Biogen to publicly commit to keeping price increases lower than the rate of inflation,” Talente said.

A recent study found that prices of several MS drugs have soared over the past decade, to an average of nearly $76,000 per patient annually.

“The pharmaceutical and biotechnology industries claim that the high prices reflect the expense of research and development and need to incentivize continued innovation. These claims are never backed up with transparent data,” said Daniel Hartung, PharmD, and Dennis Bourdette, MD, in an editorial in JAMA Neurology. “These drugs have long since recouped any cost of drug development, yet their prices have continued to rise.

“What is driving this increase is uncertain. However, the simplest explanation is that pharmaceutical and biotechnology companies increase prices because they can, they do it to increase their profit margins, and there are few limits on what they can charge.”

Biogen Involved in Illegal Co-Pay Charity

Biogen is one of three companies accused by federal prosecutors of paying a Florida-based charity to operate an illegal co-pay assistance program that helped Medicare patients buy high-priced MS drugs. The payments are considered kickbacks under a federal law that prohibits companies from subsidizing Medicare patients.

In a settlement announced Wednesday, The Assistance Fund (TAF) agreed to pay $4 million to resolve claims that it acted as a conduit for kickbacks from Biogen, Novartis and Teva Pharmaceuticals.

“Pharmaceutical companies and foundations cannot undermine the Medicare program through the use of kickbacks disguised as routine charitable donations. TAF operated as a vehicle for specific pharmaceutical companies to pay kickbacks at the ultimate expense of the American taxpayers who support the Medicare program,” said U.S. Attorney Andrew Lelling.

The DOJ has been cracking down on co-pay charities and the companies that fund them. Over $840 million in fines and penalties have been collected from eight pharmaceutical companies (United Therapeutics, Pfizer, Actelion, Jazz, Lundbeck, Alexion, Astellas and Amgen) to resolve allegations that they used third-party foundations to funnel kickbacks to patients.

What You Should Know About Neuropathy

By Barby Ingle, PNN Columnist

November is Nerve Pain Awareness Month. Or as we like to call it at iPain, “NERVEmber.”

There are dozens of chronic conditions that involve nerve pain. Neuropathy is a collection of disorders that occur when nerves of the peripheral nervous system are injured or damaged. The peripheral nerves are the ones outside of the brain and spinal cord — in our arms, legs, hands and throughout the body.

There are 3 types of peripheral nerves:  

• Autonomic nerves regulate biological activities that people do not control consciously such as breathing, digesting food and heartbeat. 

• Motor nerves control movements of muscles under conscious control such as walking, grasping things and talking.

• Sensory nerves transmit information about sensory experiences such as feeling a light touch or the pain resulting from a cut.

Some neuropathies affect all three types of nerves, others affect one or two types. Some of the diagnostic terms you might hear are predominately motor neuropathy, predominately sensory neuropathy, sensory-motor neuropathy and autonomic neuropathy.  

Neuropathy often causes pain, tingling or numbness in the hands and feet. Healthcare professionals had a longstanding belief that neuropathy pain is just a symptom of an illness and therefore not a disease. 

We now know that chronic nerve pain is a disease in itself, and the medical community and public are beginning to look at it in this way.

There are approximately 150 known types of neuropathy and the causes of many are not yet known.

Thirty percent of neuropathies are caused by diabetes, 30% are idiopathic or of an unknown cause, and the other 40% are attributed to autoimmune disorders, tumors, genetic, infections, environmental toxins and nutritional imbalances.

A great resource for patients is Dr. Norman Latov’s book, “Peripheral Neuropathy: When the Numbness, Weakness, and Pain Won't Stop.” This book helps us understand the causes of neuropathies in greater detail.

We need to increase awareness, conduct research, provide better clinical training, and better tools for diagnosing and treating neuropathy. Funding for neuropathy research is difficult to obtain because clinical professionals do not fully understand all of the complexities of neuropathy diseases and conditions. Far too often, if a patient does not have a known neuropathic condition, providers will say they could not possibly have a neuropathy.

Nerve Pain Is Not Just a Symptom

But neuropathy is not just a symptom of another disease, it can be a disease in itself.  When medical professionals fail to recognize the disease or causes of neuropathy, it leads to misdiagnosis, failure to diagnose, and delays in getting proper treatment. This can cause further damage to the patient.  

I have had some doctors tell me that neuropathy does not affect the upper body, hands or face, so I could not possibly have neuropathy and it must be something else going on. Know your limitations and your healthcare providers’ limitations. Sometimes it is difficult for them to understand all of our symptoms or the daily problems we face living with neuropathy.

It is important that we increase our communication skills as patients and caregivers. Better communication allows for better care and better answers. Too often our healthcare professionals stop short of proper diagnostic procedures due to assumptions, poor attitudes, and limited treatment options available to them. They also get pressure from insurance companies that limit payments for treatment and testing. Some providers also fail to understand the potential serious impact of these conditions going undiagnosed and undertreated.  

There are times when a doctor might believe that you can do something that you know will increase your symptoms or set off a flare. Communicate these limitations to your doctor and find out their knowledge of your condition.

Here are 5 tips to better access to proper and timely care.  

1. Seek credible information, keep your mind open to new treatments and provide copies of your research to your doctor when necessary. Remember – our providers see many patients day after day and do not always have the time to do research. You may be the first one to bring new information to them.

2. With better treatment options, we will be less frustrated as patients and can make greater progress in our goal to improve daily living.

3. Use a multidisciplinary approach to treatment. Include on your team of providers doctors who specialize in pain management, internal medicine, neuromuscular neurologists, physical therapists and psychologists/psychiatrists. Depending on the type of neuropathy you have, you may want to add doctors of immunology, radiology, oncology, hematology (liver), cardiology, pulmonology, orthopedics, urology, gastroenterology, podiatry, or other medical disciplines. 

4. When you read books by other patients or hear of new treatments in your social circles, be sure to have your own treating provider consult on those ideas. Patients are not one-size-fits-all. What works for someone else may not work for you.

5. Work with a healthcare provider who works with neuropathy patients on a regular basis. They tend to be more familiar with the daily challenges we face as patients.

Until research provides better answers and tools for diagnosing neuropathy, good doctor-patient communication is essential to diagnose and treat neuropathy in a timely manner.

Barby Ingle lives with reflex sympathetic dystrophy (RSD), migralepsy and endometriosis. Barby is a chronic pain educator, patient advocate, and president of the International Pain Foundation. She is also a motivational speaker and best-selling author on pain topics. More information about Barby can be found at her website. 

This column 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.  

Rare Autoimmune Disease Goes Into Remission After Stem Cell Therapy

By A. Rahman Ford, PNN Columnist

New research at Northwestern University and the Mayo Clinic confirms that we can heal ourselves with our own stem cells. A small study published in the journal Neurology found that treating a person with stem cells derived from their own blood or bone marrow can reverse a rare autoimmune disease called neuromyelitis optica (NMO).

Also known as Devic Disease, NMO is a chronic neurological disorder that causes inflammation in the optic nerve and spinal cord. Common symptoms are eye pain that can rapidly lead to blindness, and pain in the spine, legs or arms that can lead to paralysis. Bladder and bowel control may also be affected.

Neuromyelitis optica is often misdiagnosed as multiple sclerosis (MS). The normal course of treatment is high-dose corticosteroids and immunosuppressants.

In the study, 13 patients with NMO were first given drugs to suppress their immune system, followed by an infusion of hematopoietic stem cells (HSCT).

The results were significant and durable. After 57 months, most patients were in remission and were off all immunosuppressive drugs.

A biological marker in the blood that correlates with NMO disease activity also disappeared.

“There is marked difference between a transplant and the drug,” said lead author Dr. Richard Burt, a professor of medicine and chief of immunotherapy and autoimmune disease at Northwestern University Feinberg School of Medicine. “The transplant improved patients’ neurological disability and quality of life. They got better, and the disease maker disappeared for up to five years after transplant.”

Two of the patients relapsed after the HSCT infusion and had to go back on drug therapy.

According to Northwestern Now, Dr. Burt is a pioneer in the field of using autologous stem cells to treat autoimmune disease. Previous research by Burt has shown that HSCT can reverse relapsing-remitting multiple sclerosis, systemic sclerosis and chronic inflammatory demyelinating polyneuropathy.

When interviewed  by The Daily Northwestern about the implications of Burt’s work, Feinberg Associate Neurology Professor Dr. Roumen Balabanov predicted that chronic autoimmune diseases would be treated through “a single, radical approach” that would allow patients to live normal lives without being dependent on medications to control their symptoms.

“The point of this treatment being radical is that the patients will actually have normal lives,” Balabanov said. “They don’t have to take those lifelong medications.”

Those lifelong drugs can cost up to $500,000 per year. Conversely, the HSCT transplant costs about $100,000.

Dr. Burt is currently on sabbatical to teach his HSCT protocol at stem cell clinics around the country and to write a book. Actress Selma Blair recently had her multiple sclerosis treated by Burt’s clinic. She has been very public about her experience on social media and in interviews.

Recently the Scottish Health Technologies Group recommended HSCT be approved in Scotland to treat relapsing-remitting multiple sclerosis.

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.

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 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 MS Drugs Soars Despite Competition

By Pat Anson, PNN Editor

The cost of multiple sclerosis drugs has soared over the past decade for Medicare patients to nearly $76,000 per patient annually, according to a new study published in JAMA Neurology.

"We're not talking about patients without health insurance here," said senior author Inmaculada Hernandez, PharmD, assistant professor of pharmacy at the University of Pittsburgh. "We're talking about insured patients, under Medicare. Still, they are paying much more for multiple sclerosis drugs than they were 10 years ago."

Hernandez and her colleagues looked at Medicare Part D claims data from 2006 to 2016 for disease modifying therapies (DMTs) that reduce the frequency and severity of multiple sclerosis (MS) flare-ups. MS is a chronic and progressive disease that attacks the body’s central nervous system, causing pain, numbness, difficulty walking, paralysis, loss of vision, and fatigue.

Some of the most widely used DMTs for treating MS are Copaxone, Tecfidera and Avonex. Although there’s a fair amount of competition between the drugs -- the FDA has approved 19 DMTs for MS – prices have risen in tandem for nearly all of them.

The annual list prices of the drugs more than quadrupled over the 2006-2016 study period, far outpacing inflation.

Not only did the researchers find steep increases in list prices -- the starting point before rebates, coupons or insurance kicks in -- but also in the ultimate costs to both Medicare and its beneficiaries.

"We wanted to see how increases in list prices translated to increases in out-of-pocket spending, and we discovered that actual price increases do get passed down to patients, and that can negatively affect access," said Hernandez.

Alvaro San-Juan-Rodriguez

When it was first introduced by Biogen in 1996, Avonex had an annual list price of about $8,700. Two decades later, Avonex costs nearly $76,000 per patient per year.

“The pharmaceutical and biotechnology industries claim that the high prices reflect the expense of research and development and need to incentivize continued innovation. These claims are never backed up with transparent data,” said Daniel Hartung, PharmD, and Dennis Bourdette, MD, in an editorial in JAMA Neurology. “These drugs have long since recouped any cost of drug development, yet their prices have continued to rise.

“What is driving this increase is uncertain. However, the simplest explanation is that pharmaceutical and biotechnology companies increase prices because they can, they do it to increase their profit margins, and there are few limits on what they can charge.”

Hartung and Bourdette say neurologists who prescribe DMTs should be more aware of their cost. A generic DMT made by Mylan, for example, sells for about $2,000 a month, compared to a branded version that sells for about $6,000.  

Are You Paying Too Much for Pregabalin?

By Pat Anson, PNN Editor

It didn’t take long for cheaper generic versions of pregabalin to take a bite out of Pfizer’s monopoly of Lyrica, a drug widely used to treat fibromyalgia, diabetic neuropathy and other types of chronic pain.

Last month the U.S. Food and Drug Administration gave approval to rival drug makers to begin selling generic pregabalin after Pfizer’s patent on Lyrica expired. According to FiercePharma, Pfizer lost about a third of the market for pregabalin to 16 competitors by the end of July.  

It’s not hard to see why. According to Healthcare Bluebook, a 60-day supply of 75mg Lyrica sells for a “fair price” of $472. That compares to generic versions that sell for about $28.

“The price that most patients pay is set by insurers. The cost difference for patients between brand-name Lyrica and generic pregabalin may vary depending on the patients’ insurance plan, the state in which their prescription is filled, or the pharmacy where they pick up their prescription,” said Steven Danehy, a Pfizer spokesman.

As of August 9, Lyrica still had about 43% of the market for pregabalin, but that’s likely to change as patients, doctors and insurers became more aware of the significant difference in price.

Pregabalin is approved by the FDA for the treatment of pain associated with shingles, spinal cord injury, fibromyalgia, and diabetic peripheral neuropathy. It is also commonly prescribed "off label" for other types of chronic pain.

Pregabalin is a Schedule V controlled substance, which means it has a low potential for abuse. In recent years, however, there is growing concern that pregabalin and its sister drug gabapentin (Neurontin) are being abused and overprescribed.

The drugs, which belong to a class of nerve medication called gabapentinoids, were originally developed to treat epilepsy, not pain. Prescriptions for gabapentinoids have tripled over the past 15 years as more doctors prescribed them as “safer” alternatives to opioids.

Deaths involving gabapentinoids have increased in the UK, Australia and Canada, where some addicts have learned the drugs can heighten the euphoric effect of heroin and other opioids. The drugs were recently classified as controlled substances in the UK.

FDA Approves First Generics for Lyrica

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration has approved the first generic versions of Lyrica (pregabalin), a medication widely prescribed for the treatment of fibromyalgia, diabetic neuropathy and other types of chronic pain.

Lyrica has been a blockbuster drug for Pfizer since its approval in 2004, generating revenue of $4.6 billion annually. The recent expiration of Pfizer’s patent on Lyrica opened the door to much cheaper generic competitors.

A one year supply of Lyrica currently costs about $2,800 in the United States, according to Healthcare Bluebook, while a similar dose of pregabalin under the UK’s National Health Service costs about $74.

“Today’s approval of the first generics for pregabalin, a widely-used medication, is another example of the FDA’s longstanding commitment to advance patient access to lower cost, high-quality generic medicines,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a statement.

“The FDA requires that generic drugs meet rigorous scientific and quality standards. Efficiently bringing safe and effective generics to market so patients have more options to treat their conditions is a top priority for the FDA.”

The FDA granted approvals for generic pregabalin to 9 drug makers: Alembic Pharmaceuticals, Alkem Laboratories, Amneal Pharmaceuticals, Dr. Reddy’s Laboratories, InvaGen Pharmaceuticals, MSN Laboratories, Rising Pharmaceuticals, Sciegen Pharmaceuticals, and Teva Pharmaceuticals.

Pfizer’s patent for Lyrica CR — an extended released version of Lyrica — remains in effect until April, 2021.

Side Effects

The most common side effects for Lyrica are dizziness, somnolence, dry mouth, swelling, blurred vision, weight gain and difficulty concentrating. Lyrica’s warning label also cautions users that the drug may cause suicidal thoughts in about 1 in 500 people.

Pregabalin is classified as Schedule V controlled substance in the U.S., which means it has a low potential for abuse. In recent years, however, there is growing concern that pregabalin and its sister drug gabapentin (Neurontin) are being abused and overprescribed. The drugs were recently classified as controlled substances in the UK.

Pregabalin and gabapentin were originally developed to prevent epileptic seizures, but their use has tripled over the past 15 years as more doctors prescribed them off-label as “safer” alternatives to opioids.

A recent study in the British Medical Journal found the drugs increase the risk of suicide, overdose and traffic accidents in younger people. The risks were strongest for those taking pregabalin and were most pronounced among adolescents and young adults aged 15 to 24. Patients aged 55 and older taking gabapentinoids were not at greater risk.

Drug Maker Payments May Influence Gabapentinoid Prescribing

By Pat Anson, PNN Editor

There is growing attention being paid to doctors who accept money from pharmaceutical companies. A recent study, for example, found that doctors who receive direct payments from opioid manufacturers tend to prescribe more opioid medication than doctors who receive no such payments.

But another new study shows the same is true for doctors who prescribe an expensive class of non-opioid drugs that are widely used “off label” to treat chronic pain.

Researchers at Yale University and the University of Connecticut looked at Medicare Part D prescribing data for gabapentinoids from 2014 to 2016, comparing it with payments made to doctors from gabapentin manufacturers. Over the study period, about 51,000 physicians received $11.5 million from the drug makers, mostly for meals, beverages and gifts.

The researchers found that doctors who received the payments were more likely to prescribe a brand name gabapentinoid such as Lyrica (Pfizer), Gralise (Assertio) or Horizant (Arbor). These brand name drugs cost several hundred dollars for a one-month supply, compared to less than $20 for a one-month supply of a generic version. 

“Among physicians who prescribed gabapentinoids, receipt of payments from industry was associated with a higher likelihood of prescribing brand-name products than generic gabapentin,” researchers reported in JAMA Internal Medicine.

“Our findings raise concerns about the reasons some physicians prescribe brand-name gabapentinoids and not less-expensive generic alternatives.”

Generic drugs are generally just as effective as brand name drugs, but the differences in cost can be significant. For a Medicare beneficiary in 2016, about $2,500 a year was spent on a brand name gabapentin vs. just $89 for a generic version of the same drug.

“All of these studies have essentially the same finding -- that marketing to physicians is associated with increased sales of a company’s product and increased Medicare expenditures,” Robert Steinbrook, MD, UC San Francisco School of Medicine, wrote in a JAMA editorial.

“Association studies do not establish cause and effect, they do not account for other influences on prescribing, such as direct-to-consumer advertising, and they do not assess the appropriateness of prescriptions for individual patients. Nonetheless, the pattern is indisputable.”

Does your doctor accept industry payments? You can see for yourself on Medicare’s Open Payments database.

In addition to the costs involved, there is growing awareness that gabapentinoids are over-prescribed and not as effective for some chronic pain conditions.

The drugs were originally developed to prevent epileptic seizures, but their use has tripled over the past 15 years as more doctors prescribed them off label for a wide variety of pain conditions.

“Our findings raise concerns about the reasons some physicians prescribe brand-name gabapentinoids and not less-expensive generic alternatives.”

— JAMA Internal Medicine study

“Gabapentinoids have become frequent first-line alternatives in patients with chronic pain from whom opioids are being withheld or withdrawn, as well as in patients with acute pain who traditionally received short courses of low-dose opioid,” wrote Christopher Goodman, MD, and Allan Brett, MD, University of South Carolina School of Medicine, in a recent clinical review in JAMA Internal Medicine.

“The evidence to support off-label gabapentinoid use for most painful clinical conditions is limited. For some conditions, no well-performed controlled trials exist.”

Goodman and Brett said the 2016 CDC opioid guideline reinforces “an inflated view of gabapentinoid effectiveness” by asserting they are “first-line drugs” for neuropathic pain. Many patients who take gabapetinoids have side-effects such as dizziness or drowsiness, and there are increasing reports that the drugs are being abused and sold on the street.   

Gabapentinoids Raise Risk of Suicide and Overdose in Younger People

By Pat Anson, PNN Editor

Gabapentinoids – a class of nerve medication widely prescribed to treat chronic pain – increase the risk of suicide, overdose, traffic accidents and head or body injuries in younger people, according to a large new study published in The British Medical Journal.

Sales of the two main gabapentinoids, pregabalin (Lyrica) and gabapentin (Neurontin), have tripled in recent years in the United States, where they are often promoted in prescribing guidelines as safer alternatives to opioids.

A team of researchers followed nearly 192,000 people enrolled in the Swedish Prescribed Drug Register who filled prescriptions for gabapentinoids on at least two consecutive occasions from 2006 to 2013. That information was compared to data in the Swedish Patient Register, which collects information on hospital admissions and outpatient care, as well as the Swedish Cause of Death Register.

Over the study period, researchers found that patients taking gabapentinoids had higher rates of suicide or suicidal behavior (5.2%), unintentional overdose (8.9%), traffic accidents (6.3%) and head or body injuries (36.7%) than the general population.

The risks were strongest for people who were prescribed pregabalin and were most pronounced among adolescents and young adults aged 15 to 24.  Patients aged 55 and older taking gabapentinoids were not at greater risk.

Researchers believe the drugs may have more impact on younger people because they have faster metabolisms, which could lead to withdrawal problems that affect their impulsivity and emotions.

“Overall, gabapentinoids seem to be safe for a range of outcomes in older people. However, the increased risks found in adolescents and young adults prescribed gabapentinoids, particularly for suicidal behaviour and unintentional overdoses, warrant further research,” said lead author Seena Fazel, MD, of the University of Oxford in England.

“If our findings are triangulated with other forms of evidence, clinical guidelines may need review regarding prescriptions for young people, and those with substance use disorders. Further restrictions for off-label prescription may need consideration.”

Pregabalin is approved by the FDA to treat diabetic nerve pain, fibromyalgia, post-herpetic neuralgia caused by shingles and spinal cord injuries; while gabapentin is approved for epilepsy and post-herpetic neuralgia. Both drugs are also widely prescribed off-label to treat back pain, depression, migraine and other chronic conditions.

Gabapentinoids are increasingly being used recreationally by addicts who have found the medications enhance the effects of heroin and other opioids. The drugs were recently classified as controlled substances in the UK.

Gabapentin is not currently scheduled as a controlled substance by the DEA, while Lyrica is classified as a Schedule V controlled substance, meaning it has low potential for addiction and abuse.  

A recent clinical review found little evidence the drugs should be used off-label to treat pain and that prescribing guidelines often exaggerate their effectiveness. The CDC’s controversial opioid guideline, for example, calls gabapentin and pregabalin “first-line drugs” for neuropathic pain.

“Despite documentation that these drugs were promoted improperly for off-label treatment of pain, the recent rapid increase in prescribing of gabapentinoids suggests a persisting sense among clinicians that gabapentinoids are highly effective pain medications,” wrote Christopher Goodman, MD, and Allan Brett, MD, of the University of South Carolina School of Medicine.

“Guidelines and review articles have contributed to this perception by often uncritical extrapolation from FDA-approved indications to off-label use.”

Out-of-Pocket Costs for Neurology Drugs Rise Sharply

By Pat Anson, PNN Editor

Out-of-pockets costs for medications to treat multiple sclerosis, peripheral neuropathy and other neurologic conditions rose sharply over 12 years, according to a new study that found the average monthly cost to patients for MS drugs rose nearly 2,000 percent.

One in six people lives with a neurologic disease or disorder, according to the American Academy of Neurology. The annual cost of treating neurologic disorders in the United States is more than $500 billion.

“With many new, high-priced neurologic drugs coming to market and a recent rise in use of high-deductible insurance plans, which shift costs to patients, it is likely out-of-pocket costs will continue to increase,” said lead author Brian Callaghan, MD, of the University of Michigan in Ann Arbor.

The study was published online in the journal Neurology.

Callaghan and his colleagues examined out-of-pocket costs for over 912,000 people with MS, neuropathy, epilepsy, dementia or Parkinson’s disease who were privately insured from 2004 to 2016.

Researchers found that out-of-pocket costs for MS drugs showed the steepest monthly increase. Patients paid an average of $309 a month in 2016, compared to just $15 in 2004. Costs for MS patients in high-deductible health plans were even higher, averaging $661 per month or nearly $8,000 a year.

Co-pays and deductibles for brand name medications for neuropathy, dementia and Parkinson’s disease also rose considerably.

“Everyone deserves affordable access to the medications that will be most beneficial, but if the drugs are too expensive, people may simply not take them, possibly leading to medical complications and higher costs later,” said Ralph Sacco, MD, President of the American Academy of Neurology.

Researchers said neurologists and other physicians usually do not know the cost of drugs they prescribe, so they don’t discuss alternative medications based on a patient’s disease, insurance plan, pharmacy and deductible.

“Out-of-pocket costs have risen to the point where neurologists should be able to consider the potential financial burden for the patient when prescribing medication, but they do not have this information available to them,” Callaghan said. “Neurologists need access to precise cost information for these drugs in the clinic so when they meet with patients to make treatment decisions, they can help minimize the financial burden.”

Even when a generic version of a drug becomes available, it can take years for out-of-pocket costs to drop substantially. It took five years for out-of-pocket costs for gabapentin, for example, to drop to those of other tricyclic anti-depressants after gabapentin went generic in 2004.

A 2015 study found an “alarming” increase in costs for MS drugs and suggested the price increases were coordinated by drug companies.

A Pained Life: Fearful Fortunes

By Carol Levy, PNN Columnist

I love fortune cookies, but have no faith in the fortunes themselves. I opened a cookie recently and out came this message: “Listen to what you know instead of what you fear.”

I am going through a bad time recently. For 19 years I have had a spontaneous remission of the worst of my trigeminal neuralgia pain.

The trigeminal nerve now seems to be regenerating and it worries me. I get sporadic tingling sensations in the numbed areas of my face, the result of a procedure done in 1979. Within the last few months, the spontaneous pain has also started coming back, not in the same way, and only one or two flares were horrific.

I am very fearful all the pain will return.

My new neurologist specializes in headaches. My situation is an unknown to him. He is very nice but is essentially throwing drugs at me, a new one each time the one he just prescribed doesn't help or gives me terrible side effects. He is throwing things at the wall and hoping something will stick. I fear nothing will.

I finally found someone who specializes in trigeminal neuralgia and facial neuropathy, my disorders. She asked for a copy of my medical records so she can decide if she will accept me as a patient.  I fear she will refuse. Or if she agrees to see me will be unable to help — like almost all the others.

A woman I know has fibromyalgia and Complex Regional Pain Syndrome (CRPS). For years she has been on high dosages of Dilaudid and another strong opioid. Her doctor decided he would halve her dosages of both. She was appropriately fearful of being tapered. But to her astonishment she found she could tolerate the reductions. She is happily doing just as well on the lower dosages as she had been on the higher amounts.

A lot of what we go through is often based on fear. It is legitimate. We know what the pain is like, we know what the medications do, we know what we can and cannot do. A lot of our choices are fear based: It hurts when I do this, so therefore I will never do it again.

I am able to do so much more, feel so much better when I am on this particular medication and this particular dosage, so I will refuse any changes. I am used to this doctor/physical therapist/specialist being involved in my treatment, even though I am not always happy with them, so I will stay anyway.

It is hard to give up the fear. Pain is not like painting a room a new color and then deciding you don’t like it. You can always just repaint. But change what I am used to doing to deal with the pain? That is not so simple. My pain may increase and be even more unbearable, more daunting.

But what if I take the chance and find I am okay?

Our minds and bodies have been programmed to do all we can to avoid pain. Fear is one of the ways we deal with it. As a kid you touch a hot stove and feel the excruciating pain of a burn. You very quickly learn to fear a hot stove, the fear keeping you from hurting yourself in the same way again.

It is almost counter intuitive to heed the fortune: “Listen to what you know instead of what you fear.”

What we know is why we fear. Maybe, at least for us, the fortune should read: “'Listen to what you know, but take the chance of fear anyway.”

Carol Jay Levy has lived with trigeminal neuralgia, a chronic facial pain disorder, for over 30 years. She is the author of “A Pained Life, A Chronic Pain Journey.”  Carol is the moderator of the Facebook support group “Women in Pain Awareness.” Her blog “The Pained Life” can be found here.

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.

1 in 5 Multiple Sclerosis Patients Misdiagnosed

By Pat Anson, PNN Editor

Nearly one in five patients who are told they have multiple sclerosis are misdiagnosed with the autoimmune disease, according to a new study of patients referred to two MS treatment centers in Los Angeles. The patients spent an average of four years being treated for MS before receiving a correct diagnosis.

MS is a chronic disease that attacks the body’s central nervous system, causing pain, numbness, difficulty walking, paralysis, loss of vision, and fatigue. The symptoms are similar to those of several other chronic conditions – including neuropathy, migraine and fibromyalgia – which often leads to a misdiagnosis.

Researchers at the Cedars-Sinai Multiple Sclerosis and Neuroimmunology Center analyzed the cases of 241 patients who had been diagnosed by other physicians and then referred to the Cedars-Sinai or UCLA MS clinics.

Their findings, published in the journal Multiple Sclerosis and Related Disorders, indicate that 43 of the 241 patients (18%) with a previous diagnosis of MS did not meet the criteria for the disease.

"The diagnosis of MS is tricky. Both the symptoms and MRI testing results can look like other conditions, such as stroke, migraines and vitamin B12 deficiency," said lead author Marwa Kaisey, MD. "You have to rule out any other diagnoses, and it's not a perfect science."

The most common correct diagnoses was migraine (16%), radiologically isolated syndrome (RIS) (9%), spondylopathy (7%), and neuropathy (7%). RIS is a condition in which patients do not experience symptoms of MS even though their imaging tests look similar to those of MS patients.

The misdiagnosed patients received approximately 110 patient-years of unnecessary MS disease modifying drugs. Nearly half received medications that carry a known risk of developing progressive multifocal leukoencephalopathy, a potentially fatal brain infection.

"I've seen patients suffering side effects from the medication they were taking for a disease they didn't have," Kaisey said. "Meanwhile, they weren't getting treatment for what they did have. The cost to the patient is huge — medically, psychologically, financially."

The cost of disease modifying medications for an MS patient in the U.S. exceeds $50,000 a year. Investigators estimated that the unnecessary treatments identified in this study alone cost almost $10 million. 

Researchers hope the results of the study will lead to new biomarkers and improved imaging techniques to help prevent future MS misdiagnoses.

A similar study in 2016 also found that MS patients were often misdiagnosed. One third of the patients were misdiagnosed for a decade or longer, most took unnecessary and potentially harmful medication to treat a disease they didn't have, and some even participated in clinical trials for experimental MS therapies. About a third suffered from morbid thoughts of death.

Ambroxol: A Potential New Treatment for Chronic Pain

By A Rahman Ford, PNN Columnist

Researchers say a drug long used in cough syrup and cold medicines shows potential for treating some types of neuropathic pain.

A small study recently published in the journal Headache found that topical administration of ambroxol in a cream could significantly decrease pain in patients with trigeminal neuralgia, a chronic facial condition that can make even routine tasks such as brushing one’s teeth excruciatingly painful. 

In their review of the medical records of five trigeminal neuralgia patients, German researchers reported that all five patients experienced pain reduction with ambroxol 20% cream being applied within 30 minutes of a pain flare, with pain relief lasting from 4 to 6 hours.  In one case, pain was eliminated completely in one week.  

The results were similar to those of previous German studies and were so significant that researchers recommended that ambroxol “should be investigated further as a matter of urgency.”

Similarly, a recent study in the journal Pain Management found that application of topical ambroxol reduced spontaneous pain in several patients with complex regional pain syndrome (CRPS), a little understood nerve condition that causes chronic pain after a significant injury or surgery.  Notably, ambroxol therapy improved several other neuropathy-related conditions in CRPS patients, including edema, allodynia, hyperalgesia, skin reddening, motor dysfunction and skin temperature.

An Old Drug with a New Purpose

With a pharmacological history that can be traced back to Indian ayurvedic medicine, ambroxol was initially approved in 1978 as a medication to break down mucus and make it easier to eliminate by coughing.  It is generally administered in tablet or syrup form. 

Ambroxol is also used to treat a sore throat associated with pharyngitis, thus its potential role as a potent local anesthetic.  The drug’s anesthetic properties stem from its ability to block sodium and calcium channels that transmit pain signals.

Although the idea that ambroxol can treat a sore throat is widely accepted, its application to other forms of pain is more recent.  

Previous studies using animal models of neuropathic pain have been promising.  In a 2005 study, researchers effectively reduced – and in some cases eliminated – chronic neuropathic and inflammatory pain in rats. Indian researchers also found ambroxol effective in treating neuropathic pain in rats, attributing its success to its antioxidative and anti-inflammatory properties.  Unfortunately, human studies are few at this point.

Ambroxol and Fibromyalgia

A 2017 Clinical Rheumatology study showed that ambroxol can play a key role in treating chronic pain associated with fibromyalgia.  As reported by Fibromyalgia News Today, researchers from Mexico added ambroxol to the treatment regimens of 25 fibromyalgia patients, three times a day for one month.  At the end of the study, pain scores decreased significantly and there was also noticeable improvement in sleep disturbances, stiffness and autonomic nervous system dysfunction.  No major adverse events were reported. 

Another 2017 study supported these findings, with the authors concluding that “fibromyalgia treatment with ambroxol should be systematically investigated” because the drug “is the only treatment option used thus far that has the potential to address not just individual but all of the aforementioned aspects of pain.”

Although data on its effectiveness in humans are limited, ambroxol shows great potential in treating painful conditions for which there are currently few safe and effective options.  It is particularly attractive because it has few significant side effects, is not addictive and can be administered topically in some instances.

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.

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.

Experimental Stem Cell Therapy Reverses MS

By Steve Weakley

A small but promising study has shown that an experimental stem cell therapy can dramatically slow the progression of multiple sclerosis. Some MS patients treated with their own stem cells even experienced a reversal of their symptoms that has lasted for years.

MS is a chronic, incurable and progressive disease that attacks the body’s central nervous system, causing numbness in the limbs, difficulty walking, paralysis, loss of vision, fatigue and pain. The disease affects over 2 million people around the world.

An international team of researchers enrolled 110 patients in the study with relapsing-remitting MS, a version of the disease where symptoms appear for a few days or weeks, followed by periods of remission.

Half of the patients were treated with standard MS medications as a control group, while the other half went through a four-step experimental procedure.

The experimental group was given chemotherapy to stimulate the production of hematopoietic stem cells that recharge the immune system. Those stem cells were then removed from the patients’ blood and frozen.  After that, a more powerful round of chemotherapy was used to wipe out the patients’ damaged immune systems, and the thawed stem cells were put back into their bodies by transfusion.

Over half of the 55 patients in the control group continued to see their disease progress, while only three patients got worse in the experimental stem cell group. The other 52 had fewer symptoms and a better quality of life. The findings were reported in the journal JAMA.

“It’s the best evidence comparing stem cell transplants to standard therapy,” Harry Atkins, MD, a stem cell scientist at Ottawa Hospital in Canada told Vox . “This is one of the first pieces of proof that, yes, patients who have aggressive MS do better after a transplant than with the standard therapy.”

“The stem cell therapy gets patients off lifelong treatments and gives them results that have never been seen before with this disease,” said lead author Richard Burt, MD, a stem cell researcher and physician at Northwestern University.

One of Burt’s patients who benefited from the stem cell transplant is 28-year old Amanda Loy, who told Vox that prior to treatment she needed a cane to walk and was unable to work.  Within a year of treatment her symptoms had disappeared.

“It sounds so dramatic, but (the treatment) gave me my life back,” said Loy, who now works as a full-time teacher, runs half marathons and plays soccer with her 10-year-old son. She no longer takes MS medication.

Researchers still don’t know if the stem cell therapy will work with other forms of MS or how long the benefits will last. But it’s the first treatment that has shown the potential to actually reverse the disease.

“I do think it’s going to change the natural history of MS,” says Burt. “When you use it in the right group of patients with MS, you get these really gratifying results.”

A recent study by Australian researchers found that another experimental stem cell therapy shows promise in treating patients with progressive multiple MS, the most difficult-to-treat form of the disease.

Scientists at the University of Queensland extracted immune cells from patients who had either primary or secondary progressive MS. The cells – known as T-cells – were then “trained” in a laboratory to target and kill cells infected with the Epstein Barr virus, which has long been associated with MS.

When the altered T-cells were injected back into the bloodstream of 10 patients, seven said their symptoms improved. They had more energy, improved concentration, slept better, and had improved vision and balance. There were no serious side effects.

Scrambler Therapy Helped My Daughter Walk Again

By Reggie Greening, Guest Columnist

Beginning in August 2017, my daughter Amanda began having severe pain in her left foot after spraining her ankle. She was 20 years old at the time and described the pain as feeling as though her bones were being crushed by a red-hot anvil.

Over the next few months, Amanda started having more and more symptoms. It began with sharp pain, then discoloration, and severe swelling set in. This was about the time when she stopped being able to walk and had to be put on opioid medication in an attempt to manage the pain.

The bone crushing sensation began around the end of September, followed closely by burning pain. Amanda was still unable to walk and was taking opioids every four to six hours like clockwork. No one could figure out what was wrong or how to manage the pain other than with opioids.

While attempting to get a diagnosis, Amanda went through many rounds of testing. She had multiple x-rays, two MRIs (one with contrast dye injected intravenously), a three-phase bone scan, a nerve conductivity test, and two phases of bloodwork examined. She also went to a plethora of doctors, including a podiatrist, orthopedist, rheumatologist, dermatologist, physical therapists, homeopathic physician, chiropractor, pain management doctor, and a general medicine doctor.

The podiatrist and one of her physical therapists suspected Complex Regional Pain Syndrome (CRPS), and her podiatrist was the one who eventually determined the diagnosis of CRPS on February 16, 2018.

This spurred my research to find a more sustainable treatment option for Amanda. I spent hours searching online before discovering Scrambler Therapy.

I found a physician in New Jersey who posted videos on YouTube about Scrambler Therapy (also known as Calmare Pain Relief Therapy) and its benefits for those suffering with CRPS and other chronic nerve conditions.

We live in Louisiana, so I looked for a doctor who had a Scrambler Therapy machine closer to our home state. I eventually found a doctor in Dallas who has a machine in his office.

Amanda’s first round of treatment was administered by an osteopathic doctor in March 2018. After the fourth consecutive day of treatment, she was able to walk with the aid of crutches for the first time in seven months. The next day, after her fifth treatment, Amanda was able to walk independently. By the end of her initial round of treatment, she was entirely off opioids and NSAID pain relievers.

Our local TV station did a story about Amanda’s recovery.

Right now, the Scrambler treatment is not covered by insurance and payment for it adds up rather quickly. I am trying to get this therapy more widely acknowledged and known about so that it may become an option for others suffering with chronic neuropathic pain.

I have seen the benefits of Scrambler Therapy firsthand in my daughter. At the time of this writing, Amanda has been off opioids for two months and has been able to maintain the benefits of the initial treatment through booster treatments as needed.

Scrambler Therapy has the potential to help not just those suffering from CRPS (for whom pain relief often seems distant and hopeless), but also for those suffering from other neuropathic pain conditions.

The Greening family lives in Shreveport, Louisiana.

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.