‘Game Changing’ Study Finds Cause of Long Covid Brain Fog

By Pat Anson, PNN Editor

Inflamed and leaky blood vessels in the human brain appear to be the cause of brain fog and other cognitive issues in patients with Long Covid, according to a groundbreaking study by a team of Irish researchers.

The discovery that a viral infection may cause cognitive decline could help explain why memory loss, confusion and trouble concentrating is common in patients with other chronic illnesses, such as fibromyalgia, multiple sclerosis and chronic fatigue syndrome (ME/CFS).

Scientists at Trinity College Dublin and FutureNeuro used a specialized MRI to compare the brains of Long Covid patients with brain fog to those without brain fog.

The MRI images show how Long Covid can affect the brain’s delicate network of blood vessels. Patients with brain fog (right column) have significantly more inflammation and blood vessel leakage than those without brain fog (left column).

Patients with brain fog also had more elevated levels of glial fibrillary acidic protein (GFAP) in their blood, which is a sign of cerebrovascular damage often found in patients with repetitive head trauma.

The images and findings are published in the journal Nature Neuroscience.

“For the first time, we have been able to show that leaky blood vessels in the human brain, in tandem with a hyperactive immune system, may be the key drivers of brain fog associated with Long COVID,” said lead author Matthew Campbell, PhD, a Professor in Genetics and Head of Genetics at Trinity College, and Principal Investigator at FutureNeuro. 

“The concept that many other viral infections that lead to post-viral syndromes might drive blood vessel leakage in the brain is potentially game changing and is under active investigation by the team.” 

NATURE NEUROSCIENCE

About 10% of the people infected with the SARS-CoV2 virus develop Long Covid, a broad range of conditions that causes fatigue, shortness of breath, and muscle and joint pain. About half of Long Covid patients also report brain fog or some lingering neurological issue. 

“The findings will now likely change the landscape of how we understand and treat post-viral neurological conditions. It also confirms that the neurological symptoms of Long Covid are measurable with real and demonstrable metabolic and vascular changes in the brain,” said co-author Colin Doherty, Professor of Neurology and Head of the School of Medicine at Trinity, and Principal Investigator at FutureNeuro. 

In recent years, research has found that multiple sclerosis, lupus and other autoimmune conditions are triggered by the Epstein-Barr virus. The exact mechanism is unclear and proving there is a direct link between viral infections and brain fog has been challenging – until now.   

“Our findings have now set the stage for further studies examining the molecular events that lead to post-viral fatigue and brain fog. Without doubt, similar mechanisms are at play across many disparate types of viral infection and we are now tantalisingly close to understanding how and why they cause neurological dysfunction in patients,” said first author Chris Greene, PhD, a research fellow in the School of Genetics and Microbiology at Trinity.

The study was funded by Science Foundation Ireland, the European Research Council and FutureNeuro, a research center for chronic and rare neurological diseases.

FDA Approves First Biosimilar for Multiple Sclerosis

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration has approved Tyruko (natalizumab-sztn) as the first biosimilar for adults with relapsing forms of multiple sclerosis (MS), a move that could substantially reduce treatment costs for MS patients. Biosimilars are “highly similar” to brand-name biologic medicines, but about 30% cheaper.

"Approval of the first biosimilar product indicated to treat relapsing forms of multiple sclerosis furthers the FDA's longstanding commitment to support a competitive marketplace for biological products and ultimately empowers patients by helping to increase access to safe, effective and high-quality medications at potentially lower cost," said Sarah Yim, MD, director of the FDA’s Office of Therapeutic Biologics and Biosimilars.

Like Tysabri (natalizumab), the biologic it is modeled after, Tyruko is administered by infusion every four weeks to patients with MS, a chronic disease that attacks the body’s central nervous system, causing numbness, paralysis, loss of vision, fatigue and pain. Many MS patients experience periods of remission, followed by relapses.  

The listed cash price for a single vial of Tysabri is over $17,000, although the discounted price for insured patients is about $8,500 or $102,000 a year. Sandoz, a pharmaceutical company that specializes in biosimilars and generics, has not revealed its pricing plans for Tyruko or said when it will become available. Sandoz is a division of Novartis.

“Of the nearly one million people in the US living with multiple sclerosis, hundreds of thousands experience disease relapse. Tyruko has the potential to extend the reach of natalizumab treatment for these patients, increase healthcare savings and fuel innovation through competition in the market,” Keren Haruvi, President North America, Sandoz Inc., said in a news release.

Like Tysabri, Tyruko may also be used to treat adults with moderate to severe symptoms from Crohn's disease who have not responded well to other treatments. Crohn’s causes chronic inflammation in the digestive tract.

The FDA says patients using natalizumab products (including Tyruko and Tysabri) are at higher risk of developing progressive multifocal leukoencephalopathy (PML), a viral infection of the brain that can lead to death or severe disability. Because of that risk, prescribers must evaluate patients three and six months after their first infusion, every six months thereafter, and even after they discontinue treatment.

Growing Market for Biosimilars

Patients have long complained about the high price of MS drugs in the US, which cost two to three times more than the same drugs in Canada, Australia or the UK. One reason biologics are so expensive is that they derived from living organisms such as animal cells or bacteria, making them costly to develop.

Drug patents also last a long time – usually five years – before a “copycat” version can be introduced. Patent holders often take their competitors to court to further delay the introduction of generics or biosimilars, as was the case with AbbVie’s Humira, a biologic widely used to treat rheumatoid arthritis and other chronic inflammatory diseases. At least 9 new Humira biosimilars are finally entering the U.S. market this year.

Last week, CVS Health announced that it was launching a wholly owned subsidiary called Cordavis, which will work with drug manufacturers to commercialize biosimilars. The first biosimilar CVS plans to market in early 2024 is Hyrimoz (adalimumab-adaz), a biosimilar for Humira produced by Sandoz. CVS says the list price of the Hyrimoz will be over 80% lower than the current list price of Humira.

"Biosimilars are crucial to creating competition and reducing costs for specialty pharmaceuticals where drug prices are rising the fastest," said Prem Shah, PharmD, Executive Vice President and Chief Pharmacy Officer for CVS. "Through our direct involvement, we will expand the supply chain and ensure biosimilar availability in the market.”

As more patents expire, the biosimilars market in the U.S. is projected to grow from $6.7 billion in 2021 to more than $100 billion in 2029, according to one market forecast..

Experimental Vaccines Target Epstein-Barr Virus

By Liz Szabo, Kaiser Health News

Maybe you’ve never heard of the Epstein-Barr virus. But it knows all about you.

Chances are, it’s living inside you right now. About 95% of American adults are infected sometime in their lives. And once infected, the virus stays with you.

Most viruses, such as influenza, just come and go. A healthy immune system attacks them, kills them, and prevents them from sickening you again. Epstein-Barr and its cousins, including the viruses that cause chickenpox and herpes, can hibernate inside your cells for decades.

This viral family has “evolved with us for millions of years,” said Blossom Damania, a virologist at the University of North Carolina-Chapel Hill. “They know all your body’s secrets.”

Although childhood Epstein-Barr infections are typically mild, exposure in teens and young adults can lead to infectious mononucleosis, a weeks-long illness that sickens 125,000 Americans a year, causing sore throats, swollen glands, and extreme fatigue. And while Epstein-Barr spends most of its time sleeping, it can reawaken during times of stress or when the immune system is off its game. Those reactivations are linked to a long list of serious health conditions, including several types of cancer and autoimmune diseases.

Scientists have spent years trying to develop vaccines against Epstein-Barr, or EBV. But recently several leaps in medical research have provided more urgency to the quest — and more hope for success. In just the past year, two experimental vaccine efforts have made it to human clinical trials.

What’s changed?

First, the Epstein-Barr virus has been shown to present an even greater threat. New research firmly links it to multiple sclerosis, or MS, a potentially disabling chronic disease that afflicts more than 900,000 Americans and 2.8 million people worldwide.

The journal Science in January published results from a landmark 20-year study of 10 million military personnel that offers the strongest evidence yet that Epstein-Barr can trigger MS. The new study found that people infected with Epstein-Barr are 32 times as likely as people not infected to develop MS.

And shedding new light on the mechanisms that could explain that correlation, a separate group of scientists published a study in Nature describing how the virus can cause an autoimmune reaction that leads to MS.

The disease, which usually strikes between ages 20 and 40, disrupts communication between the brain and other parts of the body and is often marked by recurring episodes of extreme fatigue, blurred vision, muscle weakness, and difficulty with balance and coordination. At its worst, MS can lead to impaired speech and paralysis.

“Now that we know that Epstein-Barr is very tightly linked to MS, we could save a lot of lives if we develop the vaccine now.”

— Blossom Damania, Virologist

Amplifying that newfound urgency, several new studies suggest that reactivation of the Epstein-Barr virus also is involved with some cases of long covid, a little-understood condition in which patients experience lingering symptoms that often resemble mononucleosis.

And just as crucial to the momentum: Advances in vaccine science spurred by the pandemic, including the mRNA technology used in some covid vaccines, could accelerate development of other vaccines, including ones against Epstein-Barr, said Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine. Hotez co-created a low-cost, patent-free covid vaccine called Corbevax.

Some researchers question the need for a vaccine that targets a disease like MS that, while debilitating, remains relatively rare.

Eliminating Epstein-Barr would require vaccinating all healthy children even though their risk of developing cancer or multiple sclerosis is small, said Dr. Ralph Horwitz, a professor at the Lewis Katz School of Medicine at Temple University.

Before exposing children to the potential risks of a new vaccine, he said, scientists need to answer basic questions about MS. For example, why does a virus that affects nearly everyone cause disease in a small fraction? And what roles do stress and other environmental conditions play in that equation?

The answer appears to be that Epstein-Barr is “necessary but not sufficient” to cause disease, said immunologist Bruce Bebo, executive vice president for research at the National MS Society, adding that the virus “may be the first in a string of dominoes.”

‘We Could Save a Lot of Lives’

Hotez said researchers could continue to probe the mysteries surrounding Epstein-Barr and MS even as the vaccine efforts proceed. Further study is required to understand which populations might benefit most from a vaccine, and once more is known, Hotez said, such a vaccine possibly could be used in patients found to be at highest risk, such as organ transplant recipients, rather than administered universally to all young people.

“Now that we know that Epstein-Barr is very tightly linked to MS, we could save a lot of lives if we develop the vaccine now,” Damania said, “rather than wait 10 years” until every question is answered.

Moderna and the National Institute of Allergy and Infectious Diseases launched separate clinical trials of Epstein-Barr vaccines over the past year. Epstein-Barr vaccines also are in early stages of testing at Opko Health, a Miami-based biotech company; Seattle’s Fred Hutchinson Cancer Center; and California’s City of Hope National Medical Center.

Scientists have sought to develop vaccines against Epstein-Barr for decades only to be thwarted by the complexities of the virus. Epstein-Barr “is a master of evading the immune system,” said Dr. Jessica Durkee-Shock, a clinical immunologist and principal investigator for NIAID’s trial.

Both MS and the cancers linked to Epstein-Barr develop many years after people are infected. So a trial designed to learn whether a vaccine can prevent these diseases would take decades and a lot of money.

Moderna researchers initially are focusing on a goal more easily measured: the prevention of mononucleosis, which doubles the risk of multiple sclerosis. Mono develops only a month or so after people are infected with Epstein-Barr, so scientists won’t have to wait as long for results.

Mono can be incredibly disruptive on its own, keeping students out of class and military recruits out of training for weeks. In about 10% of cases, the crippling fatigue lasts six months or more. In 1% of cases, patients develop complications, including hepatitis and neurological problems.

For now, the clinical trials for Epstein-Barr immunizations are enrolling only adults. “In the future, the perfect vaccine would be given to a small child,” Durkee-Shock said. “And it would protect them their whole life, and prevent them from getting mono or any other complication from the Epstein-Barr virus.”

The NIAID vaccine, being tested for safety in 40 volunteers, is built around ferritin, an iron-storage protein that can be manipulated to display a key viral protein to the immune system. Like a cartoon Transformer, the ferritin nanoparticle self-assembles into what looks like a “little iron soccer ball,” Durkee-Shock said. “This approach, in which many copies of the EBV protein are displayed on a single particle, has proved successful for other vaccines, including the HPV and hepatitis B vaccine.”

Moderna’s experimental vaccine, being tested in about 270 people, works more like the company’s covid shot. Both deliver snippets of a virus’s genetic information in molecules called mRNA inside a lipid nanoparticle, or tiny bubble of fat. Moderna, which has dozens of mRNA vaccines in development, hopes to learn from each and apply those lessons to Epstein-Barr, said Sumana Chandramouli, senior director and research program leader for infectious diseases at Moderna.

“What the covid vaccine has shown us is that the mRNA technology is well tolerated, very safe, and highly efficacious,” Chandramouli said.

But mRNA vaccines have limitations.

Although they have saved millions of lives during the covid pandemic, the antibody levels generated in response to the mRNA vaccines wane after a few months. It’s possible this rapid loss of antibodies is related specifically to the coronavirus and its rapidly evolving new strains, Hotez said. But if waning immunity is inherent in the mRNA technology, that could seriously limit future vaccines.

Designing vaccines against Epstein-Barr is also more complicated than for covid. The Epstein-Barr virus and other herpesviruses are comparatively huge, four to five times as large as SARS-CoV-2, the coronavirus that causes covid. And while the coronavirus uses just one protein to infect human cells, the Epstein-Barr virus uses many, four of which are included in the Moderna vaccine.

Earlier experimental Epstein-Barr vaccines targeting one viral protein lowered the rate of infectious mononucleosis but failed to prevent viral infection. Targeting multiple viral proteins may be more effective at preventing infection, said Damania, the UNC virologist.

“If you close one door, the other door is still open,” Damania said. “You have to block infection in all cell types to have a successful vaccine that prevents future infections.”

Kaiser Health News is a national newsroom that produces in-depth journalism about health issues.

New Treatment Offers Hope for Lupus Patients

By Dr. Eric Morand, Monash University, Australia

When real patients have unprecedented positive outcomes to a new treatment, it’s tempting to talk about it as “breakthrough” for medical science. This describes the excitement around a new report from researchers in Germany of a radical new treatment for lupus.

The patients in the study – five people with severe lupus – went into remission following pioneering CAR T-cell treatment, which uses genetically altered cells.

What is lupus, why is this such big news, and what could it mean for other patients and diseases?

Around 5 million people are affected by some form of lupus worldwide. The most common form of lupus is technically known as systemic lupus erythematosus. Though not widespread, it is more common than multiple sclerosis (MS). Both are “autoimmune” diseases where the immune system attacks its owner instead of the germs it is supposed to fight.

MS is an autoimmune disease where the immune system attacks nerve tissue. In contrast, lupus can affect any organ in the body. Treatments for lupus have been so poor for so long that even wealthy and famous people with the disease – like pop star and actor Selena Gomez – have had organ failure resulting in the need for a kidney transplant. A lot of complicating factors have made it hard to improve outcomes for people with the disease.

Firstly, the variety of tissues lupus can affect means no two patients are exactly alike. Diagnosis is hard and often delayed. This also means we researchers have to deal with a lot of complexity as we try to work out what is causing the disease. This clinical variability makes measuring improvement in response to treatment difficult, and many clinical trials have likely failed due to measurement issues.

Second, there is variation between patients in which part of the immune system goes wrong. This means different patients will need different treatments – and we still do not know with certainty how to get this right. But progress is happening fast.

Innate and Adaptive Immunity

The immune system is in two parts, innate and adaptive.

The “innate” immune system responds fast but non-specifically to viruses and other germs that hit the body with a slug of germ-killing inflammatory proteins. The “adaptive” immune system is slower but more precise. It swings into action after the innate immune system and provides long lasting defense against the invading germ.

When you are vaccinated against a disease (such as COVID), the fever and aches you might get in the first day or two is your innate immune system at work. But the long-lasting protection from antibodies is provided by a part of your adaptive immune system, a key part of which is delivered by cells called “B cells”.

In lupus, both parts of the immune system are involved, and both have been successfully used to develop medicines. Earlier this year, the Therapeutic Goods Administration approved anifrolumab, a drug which blocks “interferon”, a crucial protein made by the innate immune system.

Another drug which works on B cells of the adaptive immune system, called belimumab, was approved a few years ago. Unfortunately, neither drug is on Australia’s Pharmaceutical Benefits Scheme yet, so access is extremely limited.

However, we now know that interferon and B cells are both important, and so very strong treatments that almost completely eradicate either could be useful. That is where this potential new treatment comes in.

Already Used to Treat Cancer

Treatments to destroy B cells are used in cancers like lymphoma. The most powerful of these uses CAR-T cells, which train a type of natural cell to be an assassin of the B cell.

CAR-T medicines are highly complex to make, and extremely expensive – but they work.

T cells are collected from the blood, then re-engineered in a special laboratory.

Now, this new report shows targeting B cells using this approach could be effective in lupus too. Building on a first-ever patient treated in this way by the same group a year ago, doctors in Germany created a “homemade” CAR-T treatment and used it in five patients with severe lupus.

Remarkably, all five patients had near complete eradication of disease, allowing them to stop conventional medicines, like steroids, with potentially harmful side effects.

What This Means for Other Patients

So what does it mean for patients in Australia? Well, most centres aren’t able to make their own CAR-T treatments, so delivering this potential treatment will require a commercial approach.

However, it might be quicker to market than other treatments in development as it takes a proven approach into a new disease, rather than being new from the ground up.

One day we might even be able to extend such treatments to other autoimmune diseases, like MS, where B cell-directed treatments have been helpful, as well as in lupus.

This would need to be balanced against risk. Importantly, short term side effects of CAR-T treatment (which include brain and bone marrow problems) can be severe. For this reason, such a treatment would only be used for the most severe cases in which standard treatments have failed, like the patients in the German trial.

Long-term side effects are also unknown at this time, and of course suppressing the immune system so profoundly in the setting of a pandemic is not without major risks.

Formal trials of a commercial CAR-T medicine for lupus are in the advanced planning stages already, and Australia is likely to be front and centre of these due to our lupus expertise and trial-friendly regulatory environment. With all these advances, we can at last tell our patients, and our friends and family with lupus, that there is light at the end of what has been a very long tunnel.

Eric Morand, MD, is a clinical rheumatologist and Head of the School of Clinical Sciences at Monash Health, Monash University in Australia.  Dr. Morand consults with companies involved in lupus drug development, including Novartis and AstraZeneca. He receives funding from Australia’s National Health and Medical Research Council and Lupus Research Alliance US, and is a Director of Rare Voices Australia.

This article originally appeared in The Conversation and is republished with permission.

Women Losing Access to Arthritis Drugs Due to Abortion Bans

By Pat Anson, PNN Editor

It didn’t take long for last month’s Supreme Court decision overturning Roe v. Wade to have a ripple effect on the U.S. healthcare system – including unintended consequences for women of childbearing age who have painful conditions such as lupus, rheumatoid arthritis, migraine and multiple sclerosis (MS).

Methotrexate and other drugs used to treat autoimmune and neurological conditions can also be used to induce abortions because they prevent cells from dividing. Although not commonly used for that purpose, methotrexate is officially listed in Texas as an “abortion-inducing drug” – an abortifacient -- putting practitioners at risk of running afoul of the state’s $10,000 bounty on anyone who helps a woman end a pregnancy after six weeks.

Even in states where abortion is legal, physicians, pharmacists and other healthcare providers have become cautious about prescribing or dispensing methotrexate.

“I received an email from my rheumatologist today that they are stopping all refills of methotrexate because it is considered an abortifacient,” a Virginia woman with lupus posted on Twitter just days after Roe was overturned. “If this is happening in a blue state with no trigger law, think of those in red states where abortion isn’t even legal. And those states that have trigger laws causing extreme and immediate loss of access.”

On the same day Roe was overturned, another poster on Twitter said his wife’s rheumatologist took all his female patients off medications that might cause a miscarriage

“So those patients are going to have to go off the drugs that were helping to control their condition and have worse health outcomes. People are going to die because of this,” he said.

The Lupus Foundation of America and Arthritis Foundation said they were aware of the situation and encouraged affected patients to contact them directly.

In an op/ed published in JAMA Neurology, neurologists at UC San Francisco School of Medicine warn the new abortion limits could have life-changing and life-threatening consequences for women with migraine, MS and epilepsy.

"Even if prescribed for a neurological condition, there are reports from patients across the country stating they are now unable to access methotrexate because it can also be used to induce abortion," wrote lead author Sara LaHue, MD, of the UCSF Department of Neurology. "This could increase risk of morbidity, mortality and irreversible disability accumulation for women with neurologic diseases."

Ironically, some treatments for neurological conditions also increase the likelihood of an unplanned pregnancy because they reduce the effectiveness of hormonal contraceptives. Physicians may become reluctant to prescribe those drugs to women of childbearing age.

Some neurologists may also rule out the use of monoclonal antibodies for women — not because they are used in abortions, but because they may harm a fetus.

"In many settings, women with MS are treated with less effective therapies, because these medications are perceived to be safer in pregnancy," said co-author Riley Bove, MD, of the UCSF Department of Neurology. "Often, neurologists are not familiar with how to time or optimize certain medications, or of their updated safety profile. The reversal of Roe v. Wade may reinforce decisions to stick with the less effective therapies, which may result in irreversible disability for some women with MS."

This week the Health and Human Services Department (HHS) warned retail pharmacies they are at risk of violating federal civil rights law if they deny women access to medications used in abortions. The warning specifically mentions methotrexate when its prescribed to someone with rheumatoid arthritis or some other disabling condition.

“If the pharmacy refuses to fill the individual’s prescription or does not stock methotrexate because of its alternate uses, it may be discriminating on the basis of disability,” HHS said..

If I Have MS or an Autoimmune Condition, Should I Get the Covid Vaccine?

By Judith Graham, Kaiser Health News

As public demand grows for limited supplies of covid-19 vaccines, questions remain about the vaccines’ appropriateness for older adults with various illnesses, including those with cancer, multiple sclerosis or autoimmune conditions.

Recently, a number of readers have asked me whether older relatives with these conditions should be immunized. This is a matter for medical experts, and I solicited advice from several. All strongly suggested that people with questions contact their doctors and discuss their individual medical circumstances.

Experts’ advice may be helpful since states are beginning to offer vaccines to adults over age 65, 70 or 75, including those with serious underlying medical conditions. Twenty-eight states are doing so, according to the latest survey by The New York Times.

Q: My 80-year-old mother has chronic lymphocytic leukemia. Should she get vaccinated?

First, some basics. Older adults, in general, have responded extremely well to the two covid-19 vaccines that have received special authorization from the Food and Drug Administration. In large clinical trials sponsored by drug makers Pfizer and Moderna, the vaccines achieved substantial protection against significant illness, with efficacy for older adults ranging from 87% to 94%.

But people 65 and older undergoing cancer treatment were not included in these studies. As a result, it’s not known what degree of protection they might derive.

Dr. Tobias Hohl, chief of the infectious diseases service at Memorial Sloan Kettering Cancer Center in New York City, suggested that three factors should influence patients’ decisions: Are vaccines safe, will they be effective, and what is my risk of becoming severely ill from covid-19?

Regarding risk, he noted that older adults are the people most likely to become severely ill and perish from covid, accounting for about 80% of deaths to date — a compelling argument for vaccination.

Regarding safety, there is no evidence at this time that cancer patients are more likely to experience side effects from the Pfizer-BioNTech and Moderna vaccines than other people. “We are confident that these vaccines are safe for [cancer] patients,” including older patients, said Dr. Armin Shahrokni, a Memorial Sloan Kettering geriatrician and oncologist.

The exception, which applies to everyone, not just cancer patients: people who are allergic to covid-19 vaccine components or who experience severe allergic responses after getting a first shot shouldn’t get covid-19 vaccines.

In new guidelines published late last week, the National Comprehensive Cancer Network, an alliance of cancer centers, urged that patients undergoing active treatment be prioritized for vaccines as soon as possible. A notable exception:  Patients who’ve received stem cell transplants or bone marrow transplants should wait at least three months before getting vaccines, the group recommended.

The American Cancer Society’s chief medical and scientific officer, Dr. William Cance, said his organization is “strongly in favor of cancer patients and cancer survivors getting vaccinated, particularly older adults.”

Q: Should my 97-year-old mom, in a nursing home with dementia, get the covid vaccine?

The federal government and all 50 states recommend covid vaccines for long-term care residents, most of whom have Alzheimer’s disease or other types of cognitive impairment. This is an effort to stem the tide of covid-related illness and death that has swept through nursing homes and assisted living facilities — 37% of all covid deaths as of mid-January.

The Alzheimer’s Association also strongly encourages immunization against covid-19, “both for people [with dementia] living in long-term care and those living in the community, said Beth Kallmyer, vice president of care and support.

Minimizing suffering is a key consideration, said Dr. Michael Rafii, associate professor of clinical neurology at the University of Southern California’s Keck School of Medicine.

“Even if a person has end-stage dementia, you want to do anything you can to reduce the risk of suffering. And this vaccine provides individuals with a good deal of protection from suffering severe covid,” he said. “My advice is that everyone should get vaccinated, regardless of what stage of dementia they’re in.”

Q: I’m 80 and I have Type 2 diabetes and an autoimmune disease. Should I get the vaccine?

There are two parts to this question. The first has to do with “comorbidities” — having more than one medical condition. Should older adults with comorbidities get covid vaccines?

Absolutely, because they’re at higher risk of becoming seriously ill from covid, said Dr. Abinash Virk, an infectious diseases specialist and co-chair of the Mayo Clinic’s covid-19 vaccine rollout.

“Pfizer’s and Moderna’s studies specifically looked at people who were older and had comorbidities, and they showed that vaccine response was similar to [that of] people who were younger,” she noted.

The second part has to do with autoimmune illnesses such as lupus or rheumatoid arthritis, which also put people at higher risk. The concern here is that a vaccine might trigger inflammatory responses that could exacerbate these conditions.

Philippa Marrack, chair of the department of immunology and genomic medicine at National Jewish Health in Denver, said there’s no scientifically rigorous data on how patients with autoimmune conditions respond to the Pfizer and Moderna vaccines.

So far, reasons for concern haven’t surfaced. “More than 100,000 people have gotten these vaccines now, including some who probably had autoimmune disease, and there’s been no systematic reporting of problems,” Marrack said. If patients with autoimmune disorders are really worried, they should talk with their physicians about delaying immunization until other covid vaccines with different formulations become available, she suggested.

Last week, the National Multiple Sclerosis Society recommended that most patients with multiple sclerosis — another serious autoimmune condition — get the Pfizer or Moderna covid vaccines.

“The vaccines are not likely to trigger an MS relapse or to worsen your chronic MS symptoms. The risk of getting COVID-19 far outweighs any risk of having an MS relapse from the vaccine,” it said in a statement.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente.

Survey Finds Over Half of MS Patients Abused by Caregivers

By Pat Anson, PNN Editor

People with multiple sclerosis already have enough problems living with a progressive disease and sky-high medical bills. But now there’s word that many of them are being abused by their own caregivers.   

Researchers at the University of California, Riverside surveyed 206 patients with advanced MS and found that over half of them were being abused in some way by an unpaid caregiver who was often a member of their own family. The mistreatment ranged from psychological (44%) and financial abuse (25%) to neglect (16.5%) and physical abuse (11%). Over 8 percent of patients said they were abused sexually.   

"We knew we would find some level of abuse and neglect, but we were surprised by how prevalent it is," said Elizabeth Morrison-Banks, MD, a health sciences clinical professor at the UC Riverside School of Medicine, who led the study. "The findings of this study represent a collective cry for help from so many families affected by multiple sclerosis across the United States."

MS is a chronic and disabling autoimmune disease that attacks the body’s central nervous system, causing pain, numbness, difficulty walking, paralysis, loss of vision and fatigue.

"Some people live with MS for many years but with milder symptoms, and they may remain completely self-sufficient and never require a caregiver,” Morrison-Banks explained. “Others are less fortunate and develop neurological disability that can make them vulnerable to abuse and neglect if they are unable to move around independently, take care of their own finances, or get away from the situation when family conflict escalates. These problems are compounded if the person with MS and family lack financial resources."

A recent study found over 75% of American adults with MS face financial hardship that has forced them to cut spending on food, clothing and housing. Many have gone into debt or filed for bankruptcy, and over a third have delayed or stopped filling prescriptions because they can’t afford them. The average cost of disease-modifying MS drugs is about $76,000 a year.

For MS patients who are struggling financially, hiring a professional caregiver is not an option, so many have to rely on family caregivers.

"Some family caregivers are also working full time, caring for children or other family members, and sometimes dealing with health issues of their own," explained Morrison-Banks. "I want to emphasize that the majority of family caregivers do not mistreat those they care for, even in situations that can be very challenging. Nonetheless, it is important to recognize the risk factors for mistreatment of people with disabilities, and do what we can to identify, mitigate, and prevent abuse and neglect."

Other risk factors for mistreatment include MS patients with higher levels of cognitive impairment, caregivers having a mental health problem, alcohol use by the caregiver or patient, and low levels of social support within the family.

"Being a full-time family caregiver for someone with substantial neurological disability often presents significant challenges," Morrison-Banks said. "Many families take these challenges in stride, but others end up in situations of abuse and/or neglect."

The survey findings have been published in the journal Multiple Sclerosis and Related Disorders. The research paper is believed to be the first to document the nature and extent of caregiver mistreatment of MS patients in the United States.

The survey did not include patients who had paid caregivers or trained clinicians. A study of paid caregivers is an important next step for the research team. The National Multiple Sclerosis Society funded the UC Riverside study.

Over 75% of MS Patients Face Financial Hardship

By Pat Anson, PNN Editor

Over 75% of American adults with multiple sclerosis face financial toxicity or hardship that has forced them to cut spending on food, clothing and housing. Many have gone into debt or filed for bankruptcy, and over a third have delayed or stopped filling prescriptions because they can’t afford them.

The findings come from a survey of 243 multiple sclerosis (MS) patients conducted by the Harvey L. Neiman Health Policy Institute. The study is the first of its kind to evaluate how financial hardship is forcing MS patients to forego treatment and make drastic changes in their lifestyles and spending.

In recent years, the cost of prescriptions for many disease-modifying MS drugs has nearly tripled to about $76,000 a year. While insurance pays for most of it, many patients are overwhelmed by deductibles and other out-of-pocket expenses. The lifetime cost of treating MS in the United States is estimated at over $4 million per patient.

“Over the last 20 years, higher out-of-pocket costs for advanced imaging tests and increased cost sharing have caused the financial burdens on MS patients to escalate. Among medically bankrupt families, MS is associated with the highest total out of-pocket expenditures exceeding those of cancer patients,” said lead author Gelareh Sadigh, MD, an assistant radiology professor at Emory University School of Medicine.

“Our study results demonstrate the high prevalence of financial toxicity for MS patients and the resulting decisions patients make that impact their health care and lifestyle.”

More Debt, Less Spending

The findings, published in the Multiple Sclerosis Journal, show that over half of MS patients (56%) reported decreases in their income due to disability, unemployment or retirement. To make ends meet, many cut spending on food and clothing (35%) and leisure activities (50%) or withdrew money from their savings (40%) and retirement accounts (15%). Others went into debt by borrowing money (19%) or charging their credit cards (30%).

Over a third of MS patients decided to forego some type of medical care or treatment, such as not filling a prescription (16%), skipping doses (13.5%) or stopped taking medication (13%).

“These data underscore the need for shared decision-making and an awareness of patient financial strain when planning treatment strategies,” said co-author and Neiman Institute researcher Richard Duszak, MD, a professor and vice chair for health policy at Emory University. “In addition to the impact on adherence, financial toxicity was associated with significantly lower physical health-related quality of life, demonstrating the broad consequences of treatment costs for many MS patients.”

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. Disease modifying therapy (DMT) reduces the frequency and severity of MS flare-ups, but many patients can’t afford the drugs.

A 2019 survey by the National Multiple Sclerosis Society found that 40% of MS patients who take a DMT drug altered or stopped taking their medication due to the high cost. According to Healthcare Bluebook, a 30-day supply of a brand name DMT like Gilenya costs about $8,845, or over $106,000 a year.

Criticism of the high cost of MS drugs is growing. Last year 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 rebuke from the National MS Society, which released a statement that accused Biogen of price gouging.

Cost of MS Drugs Nearly Tripled

By Pat Anson, PNN Editor

The cost of prescriptions for disease-modifying multiple sclerosis (MS) drugs nearly tripled in the last decade, even with the introduction of cheaper generic versions, according to a new study funded by the National Multiple Sclerosis Society.

Researchers found spending on 15 MS drugs in the Medicaid program increased from $453 million in 2011 to $1.32 billion in 2017.

“Most of these drugs cost more than $70,000 per year on average and costs for these drugs are among the highest drug cost areas for private insurers as well as Medicare and Medicaid,” said Daniel Hartung, PharmD, of Oregon State University in Portland. “Unfortunately for people with MS, the introduction of a generic drug had a minimal effect on prices overall.”

Hartung and his colleagues found that when a generic version of the drug glatiramer acetate (Copaxone) was introduced in 2015, it was only 15 percent cheaper than the brand name drug made by Teva Pharmaceuticals.

Teva also worked to maintain its market share by encouraging doctors and patients to switch from a 20 mg dose of Copaxone to a 40 mg dose, which was not interchangeable with the new generic.

A second company introduced a generic version of glatiramer acetate in October 2017. Only then did the cost start to come down and generic versions started to get a greater share of the MS market.  

“After our study was complete, the company that introduced the second generic drug dropped its costs significantly, making it the lowest cost disease-modifying drug for MS on the market,” Hartung said. “Despite this, there is an urgent need for more robust competition from generics within these MS drugs.”

A similar study published last year found that Medicare paid nearly $76,000 annually per patient for disease modifying therapy (DMT), which reduces the frequency and severity of 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.

Many Patients Can’t Afford DMT Meds

A recent survey by the National Multiple Sclerosis Society found that 40% of MS patients who take a DMT drug altered or stopped taking their medication due to the high cost. Only 11% said they could afford the medication without financial assistance.

“People with MS are paying the price, not only financially, but also physically and emotionally,” Bari Talente, executive vice president of advocacy for the National MS Society said in a statement.

“When someone alters or stops the use of their DMT, it can lead to increased symptoms, relapses, stress and anxiety. We need to make these medications affordable and accessible so people already facing a chronic illness don’t have to deal with deciding between buying groceries for their families or paying for their medication.”

The FDA recently approved the first generic versions of Gilenya (fingolimod) for the treatment of relapsing forms of multiple sclerosis (MS). A 30-day supply of brand name Gilenya 0.5mg capsules currently costs about $8,482, according to Healthcare Bluebook, or nearly $102,000 a year.

Few people actually pay the full amount for a DMT drug. About 45% of MS patients do not pay anything out-of-pocket for their DMT. The average annual cost among those who do pay is about $2,300.

Research Explores Cannabis as Treatment for MS, Alzheimer’s and Huntington’s Disease

By Pat Anson, PNN Editor

The University of Alberta is partnering with a Canadian cannabis company in three research projects exploring the use of medical cannabis for the treatment of multiple sclerosis, Alzheimer’s and Huntington’s diseases. 

Atlas Biotechnologies is investing nearly $300,000 over the next two years to fund the studies. Atlas operates a 38,000 square foot cannabis production facility near Edmonton and will supply customized blends of cannabis products to U of A researchers.

“People are touting (cannabis) for all kinds of things, but without solid scientific evidence,” said Ross Tsuyuki, PharmD, chair of the Department of Pharmacology at U of A. “But there likely are benefits for some conditions.”

The most well-known chemical compounds in cannabis are tetrahydrocannabinol (THC) and cannabidiol (CBD), but the plant has hundreds of other active biological chemicals, each with the potential of having therapeutic benefits. The goal of the research is to identify what specific compounds or combinations of compounds are effective.

“We've got to figure out the best combination of those compounds and how they're actually working in people,” Jeffrey Gossain, Atlas’ chief operating officer, told Folio, the University of Alberta's news site.  “A lot of people will tell you, 'My mom had cancer’ or, ‘My friend had an illness, and they took cannabis and it helped.’ But then for other people they don't have as effective results. 

“Part of the problem is that you don't really know what product they took, how they dosed it or the combinations of chemicals in the product that helped. It's not as simple as just saying, ‘The plant's got THC and CBD.’ You've got to get a lot more detailed than that.”

The research will examine whether CBD and other cannabinoids can relieve pain in patients with multiple sclerosis; if cannabis can reduce neuroinflammation and degeneration of the brain caused by Huntington's disease; and if cannabinoids have neuroprotective activity in models of Alzheimer’s disease.

“Alzheimer's disease, chronic pain, multiple sclerosis and Huntington's disease are all devastating conditions that don't have a lot of effective treatments,” said Tsuyuki. “If we find something, even if it works just a little, that could be an enormous advance for patients. But we have to do our homework first, and that is where we're starting.”

In addition to its partnership with the U of A, Atlas is collaborating with Harvard Medical School in developing cannabis products for pain and other neurological conditions.

A recent study found that medical cannabis is mildly effective in relieving pain and other symptoms in patients with multiple sclerosis (MS). Spanish researchers analyzed 17 clinical trials involving different combinations of THC and CBD, and found cannabis had limited effectiveness in relieving pain, muscle spasticity and bladder dysfunction.

MS is a chronic and incurable disease which attacks the body’s central nervous system, causing numbness in the limbs, difficulty walking, paralysis, loss of vision, fatigue and pain.

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.

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.  

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.

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.

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.