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.

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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.  

The Future of CBD

By Roger Chriss, PNN Columnist

Is CBD a medical miracle or just another over-hyped health fad? The cannabinoid known as cannabidiol (CBD) is appearing in hundreds of foods, drinks and health products – even though we know little about its potential harms and benefits. Recent research runs the gamut, suggesting that CBD can fight superbug infections or cause liver damage.

A review of 35 clinical studies found CBD effective in treating anxiety and epilepsy, but there was no evidence it works for diabetes, Crohn's disease, ocular hypertension, fatty liver disease or chronic pain.

But there may be some untapped possibilities. Ingenious bench science and clinical research is improving our understanding of how CBD acts in the body, which is leading to new drugs with impressive potential for treating serious illnesses.

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How Does CBD Work?

In simple terms, no one knows. CBD doesn’t seem to act directly on the cannabinoid receptors CB1 and CB2, although it does have some activity in serotonin 5HT1A, GRP55, and TRPV1 receptors that regulate anxiety, inflammation and pain sensation.  

Although none of these receptors is directly involved in seizures, CBD is being used successfully to treat epilepsy and other seizure disorders. CBD in the highly-purified form Epidiolex is FDA-approved as “add-on therapy” for Dravet syndrome and Lennox-Gastaut syndrome, two rare childhood seizure disorders.

New pharmacological research suggests that CBD may reduce seizure frequency through a “drug-drug interaction” rather than as an anti-seizure medication in and of itself.

In other words, whatever CBD is doing probably involves a host of small nudges often described as endocannabinoid activity. This makes for a complex set of interactions and contraindications, many still not well understood.  

New Drugs Derived from CBD

CBD acts on too many receptors in too many ways to make for predictable clinical effects. And at high doses CBD is potentially toxic to both the liver and nerves over the long term. But understanding this activity is helping guide research.

A potent CBD-derived compound called KLS-13019 has a more targeted effect on receptors and is being studied as a treatment for some neurological conditions.

Even more promising is EHP-101, an oral formulation of a synthetic CBD molecule that helped repair myelin around damaged nerve fibers in mice. This is an exciting if preliminary finding that may have potential for treating multiple sclerosis (MS). Emerald Health Therapeutics is planning to launch a Phase II clinical trial of EHP-101 in MS patients by the end of the year.

“Restoring the myelin sheath around nerves, or remyelination, would be considered a ‘Holy Grail’ outcome in the treatment of MS,” Jim DeMesa, MD, CEO of Emerald Health Pharmaceuticals, said in a statement. “These preclinical data provide the first evidence of remyelination with our lead clinical-stage drug product candidate and provide promising evidence for the possibility to treat, and potentially reverse, several forms of MS in the future.”

CBD itself may have uses as a wellness product for otherwise healthy people. It is certainly an appealing indulgence. But CBD-derived products that avoid the complications of CBD while taking advantage of specific activity learned from studying CBD are showing great promise.

New drugs replace old drugs all the time. Aspirin was outclassed by ibuprofen and naproxen, barbiturates by benzodiazepines, and MAO inhibitors by TCAs and more recently SSRIs. CBD may fade as a pharmaceutical, but its descendants could be the wonder drugs that CBD is often touted as.

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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.

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.

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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.

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.

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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.

How Sodas and Smoking Worsen Disability

By Pat Anson, PNN Editor

Most doctors will tell you that smoking and drinking sweetened beverages like soda every day will lead to poor health. They can also worsen your risk of disability if you have rheumatoid arthritis or multiple sclerosis, according to new studies.

Researchers in Germany wanted to know how diet can affect the progression of multiple sclerosis (MS), a chronic disease that attacks the body’s central nervous system, causing numbness, difficulty walking, paralysis, loss of vision, fatigue and pain.  

They surveyed 135 MS patients to see how close their diet was to the Dietary Approaches to Stop Hypertension (DASH) diet – which limits foods that are high in saturated fat and sugar – and recommends whole grains, fruits and vegetables, low-fat dairy products, lean meats, poultry and fish, nuts and legumes.

Researchers did not find a link between what the participants ate and their level of disability, but there was a strong association with what they drank.

"While we did not find a link with overall diet, interestingly, we did find a link with those who drank sodas, flavored juices and sweetened teas and coffees," said study author Elisa Meier-Gerdingh, MD, of St. Josef Hospital in Bochum, Germany.

MS patients who consumed the largest amounts of sugar-sweetened beverages – averaging about 290 additional calories per day -- were five times more likely to have severe disability than people who rarely drank sweetened beverages.

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"While these results need to be confirmed by larger studies that follow people over a long period of time, and the results do not show that soda and sugar-sweetened beverages cause more severe disability, we do know that sodas have no nutritional value and people with MS may want to consider reducing or eliminating them from their diet," said Meier-Gerdingh, who will present her findings at the American Academy of Neurology's annual meeting in Philadelphia in May.

Smoking Worsens Risk of Rheumatoid Arthritis

Previous studies have also found that smoking increases your chances of having MS and several other chronic pain conditions.

A new study by researchers at Brigham and Women's Hospital in Boston demonstrated for the first time that women who stop smoking can reduce their risk of developing the most severe form of rheumatoid arthritis (RA). But it takes time to have a beneficial effect.

"Ours is the first study to show that a behavior change can reduce risk for seropositive RA. Risk isn't just about genes and bad luck--there's a modifiable environmental component to the onset of this disease and a chance for some people to reduce their risk or even prevent RA," said corresponding author Jeffrey Sparks, MD, of the Division of Rheumatology, Immunology and Allergy at the Brigham.

Sparks and colleagues analyzed data from the Nurses' Health Study, which tracked the long-term health of registered nurses from across the U.S.  Brigham researchers identified over 1,500 nurses who developed RA, but they were most interested in those with "seropositive" RA as opposed to "seronegative" RA. Patients with seropositive RA generally have more severe joint deformities and disability.

For seropositive RA, the risk of disability began to go down about five years after women quit smoking and continued to decrease the longer they stayed non-smokers. Participants who quit for good reduced their risk of seropositive RA by 37 percent after 30 years. The team did not find any association between seronegative RA and smoking.

"One of the lessons here is that it takes sustained smoking cessation to reap the full benefit," said Sparks, who published his findings in the journal Arthritis Care & Research.

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"Whereas for other diseases, such as cardiovascular disease, quitting smoking can provide a more immediate effect, here we're seeing benefits decades later for those who quit smoking permanently."

RA is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing pain, inflammation and bone erosion. While the biological mechanisms that link smoking and the development of RA are unclear, Sparks believes that smoking may contribute to the formation of RA-related antibodies that increase inflammation.

In future studies, Brigham researchers want to extend their investigations to include men and to see if smoking cessation can prevent the formation of RA-related antibodies and stop progression of the disease.

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.

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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.

Puppy Medicine

By Jennifer Hochgesang, Guest Columnist  

I was miserable. My trigeminal neuralgia pain from multiple sclerosis was still uncontrolled, leaving me mostly housebound. I had also just been diagnosed with vestibular migraines, which cause vertigo. Sometimes the vertigo was so extreme I was unable to walk, the world moving like a drunken carnival ride that never stopped even when my eyes were closed.  

And while the trigeminal neuralgia (TN) was on the right side of my mouth, I had just gotten ulcers out of nowhere on the left side. Anytime I drank something I felt a blind searing pain that took minutes to subside.

I was just barely pushing through, not sure how much more I could take. But I had an appointment to see a puppy at a nearby animal shelter.

I have had dogs all my life. Each one has been a part of the family and amazing creatures: loving, smart, playful and giving. My last dog, Aequoris, passed away two years ago and her sister Zola a little before that. I needed time before getting another dog. But as I went through this year in the worst pain of my life, I started to slowly think about getting a dog again.

But I had many questions to ask myself: Was I well enough to care for a dog? Could I afford a vet? Would the dog get enough exercise? Did I have help for the times I was too sick to care for it? Were there walking services in my area or boarding services if I had to go to the hospital? Would pet insurance cover those situations? Would my family members want a dog and be willing to help?

Even as I answered all those questions on the way to the shelter, I almost cancelled. I just felt so physically awful and it was hard to think of enjoying a puppy.   

When we got there, they put us in a small room so we could meet the puppy and get to know her a little. She was an 11-week old rescue from a litter of five. They said she was a Spaniel mix, but really they had no idea what breed she was.

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When they brought her in, my first thought was that she was pretty funny looking. Then she actually ran up to me and kissed me right on the left side of my mouth, the one that doesn’t have my TN. It was like she knew! I couldn’t believe it!

I held her and smelled that sweet puppy smell. She wasn’t funny looking after all. She was beautiful. She had dots of brown over her eyes, silky black fur down her back, and fawn-like legs with spots everywhere.

We played and I fell in love within seconds. I watched her play, moving like a little infant excited with the world. I laughed as she tried to catch a ball and fell, and was so moved when she came to me for comfort.

Suddenly I realized I wasn’t in as much pain! Holding her, rubbing her soft fur and watching her jump around just did something for me – like it was medicinal. She was helping me. I knew at that moment she would bring that gift to me and in return I would do whatever I could to make sure she was cared for: vet visits, exercise, training and love. I named her Sasha: helper of womankind.

Sasha is now almost six months old. She is crazy smart and learned sit, down, and up in the air the first day. I have also started working with a trainer so she doesn’t touch the right side of my face and set off a TN attack.

I can have Sasha off leash in the backyard and throw the ball for her to catch with my 7-year-old daughter, who thankfully runs like crazy with her.

But she still rings the bell to go outside seven times an hour and tries to eat my socks no matter how many times I say no. She grabs tissues and runs so fast, dodging furniture and ducking under and over until you want to pull your hair out.

But then you leave the room for one second and come back to find her butt wiggling, tail thumping on the floor, and plaintively whinnying, “I’m so happy to see you. I missed you so much.”

Sasha has the sweetest face and when she lays next to you with her head curled in your lap letting you pet her, looking up at you -- it’s just pure love.

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Is it a coincidence that in the past five weeks I’ve finally found the food triggers for my trigeminal neuralgia? I’ve stopped eating dairy, citrus, chocolate, caffeine and sugar. My pain has gone down so much. It’s like night and day since I got Sasha. I still need to work with a nutritionist to make sure I’m eating the right foods, but for now this is working for me.

Sasha is still a baby so I haven’t expected her to do much more than be a cute furball. But one day while I was working on my iPad, she came and positioned herself right in my lap. I had to move her over a little so I could work. She still stuck like glue to the left side of my body with her head on my leg or arm throughout the day. I thought she was just tired.

Then slowly my TN pain began to increase, until I had a really awful volley of attacks every few minutes. Sasha moved closer and closer to my face as the pain got worse. During one brutal attack she kissed me on the left side and I was so thankful. She actually understood I was in pain and where it was. She knew when it was getting worse. And all she wanted was to heal and comfort me.  

As I write this, Sasha is sitting right here next to me chewing on a rawhide pretzel. She brought seven toys up on the couch in case she gets bored with the pretzel and wants me to throw something. I take a break from writing to pet her and sometimes she will turn over and give me her belly to rub. Soon she’s going to get up and ring that bell to go outside in the light snow.

She is just the most beautiful thing.

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Jennifer Hochgesang lives in Illinois. Jennifer has multiple sclerosis, trigeminal neuralgia and vestibular migraines.

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.