Biologic Drug May Prevent Rheumatoid Arthritis

By Pat Anson, PNN Editor

A biologic drug used to treat rheumatoid arthritis and other autoimmune conditions appears to be effective in preventing the disease from developing, according to the results of a mid-stage clinical trial.

Abatacept is a disease modifying antibody that was approved by the FDA in 2005 to treat moderate to severe rheumatoid arthritis (RA). Sold under the brand name Orencia, the drug interferes with the immune activity of T-cells, which helps reduce the inflammation and joint pain caused by RA. Abatacept is also used to treat psoriatic arthritis and juvenile idiopathic arthritis.

In the phase 2b clinical trial, 213 adult patients in the UK and the Netherlands at high risk of RA were randomly divided into two groups. One group was given weekly injections of abatacept for a year, while the other group received a placebo. Their progress was followed for another 12 months.

The study findings, recently published in The Lancet, show that only 6% of participants in the abatacept group were diagnosed with RA during the treatment period, compared to 29% in the placebo group. After 24 months, 25% of patients in the abatacept group progressed to RA, compared to 37% in the placebo group.

Patients on abatacept also reported lower pain scores, better physical function and quality of life, and had less inflammation in their joints.

“This is the largest rheumatoid arthritis prevention trial to date and the first to show that a therapy licensed for use in treating established rheumatoid arthritis is also effective in preventing the onset of disease in people at risk,” lead author Andrew Cope, PhD, head of King’s College London Center for Rheumatic Diseases, said in a news release.

“These initial results could be good news for people at risk of arthritis, as we show that the drug not only prevents disease onset during the treatment phase but can also ease symptoms such as pain and fatigue.”

One of the patients who participated in the trial was Philip Day, a 35-year-old software engineer and soccer player who had to give up the sport due to joint pain. He was considered at high risk of RA.

“The pain was unpredictable, it would show up in my knees one day, my elbows the next, and then my wrists or even my neck. At the time, my wife and I wanted to have children and I realized my future was pretty bleak if the disease progressed,” Day said.

“Enrolling in the trial was a no-brainer; it was a ray of hope at a dark time. Within a few months I had no more aches or pains and five years on I’d say I’ve been cured. Now, I can play football (soccer) with my three-year-old son and have a normal life.”

There are a few caveats about abatacept. A year’s worth of treatment in the U.S. costs about $37,500, depending on insurance. Most insurers consider abatacept a second or third-line therapy, and won’t pay for it unless other medications are tried first.

Like other biologic drugs that suppress the immune system, abatacept can have adverse side effects such as respiratory tract infections, pneumonia, flu, dizziness, nausea and diarrhea. Abatacept can also interfere with the effectiveness of vaccines.

Those are risks that many RA patients may be willing to accept, given the progressive nature of the disease, which cannot be cured and often results in disability.

“There are currently no drugs available that prevent this potentially crippling disease. Our next steps are to understand people at risk in more detail so that we can be absolutely sure that those at highest risk of developing rheumatoid arthritis receive the drug,” said Cope.

The abatacept study was funded by Bristol Myers Squibb, the maker of Orencia.

My Story: Riding the Merry-Go-Round of Pain Care

By Christopher Matthews, Guest Columnist

About two and a half years ago, I began to feel a tight painful knot on the side of my neck. Any movement would trigger an intense shock up the back of my skull to the top of my head. Ultrasound, MRI and X-ray scans all came back negative, so we tried anti-inflammatory medications, ice, deep tissue message, chiropractic, and some lifestyle changes.

Over the next few months, the pain began radiating to my cervical spine and intensified. No OTC pain medication was touching this pain.  It felt like a hot steak knife was lodged in my back. The constant, unbearable pain and symptoms of neuropathy seemed to indicate that some minor disc bulging in my spine may be more severe than we thought.

It took 4 months to get an appointment with a specialist in neurosurgery at a prominent hospital in Massachusetts. The surgeon looked at me for 5 minutes and ordered more tests. They found some abnormalities in my arms and legs, but the imaging didn’t warrant surgery. They recommended that I see a neurologist, which meant waiting another 5 months for an appointment.

During the interim, my primary care doctor wanted to be proactive. She was the only one taking me seriously. I did physical therapy 3 days a week and about a dozen courses of oral steroids. I was hopped up on cortisone for months. I also had a series of injections into my spine. None of it seemed to help.

I finally saw the neurologist, who ordered another MRI, which showed the bulging discs in my back were getting worse. But I was still not a candidate for surgery.

I’ve now been hospitalized 4 times due to loss of function, pain flares or passing out from pain in public places. The pain is that bad. Some days I can’t even get out bed because my knees won’t work. Some days I have close to no use of my arms, because my elbows are on fire. I’ve been getting more and more bacterial infections.          

My primary care doctor is the only one who believes my pain is real. She showed mercy and set up a pain management contract with me. We started with 5mg hydrocodone/acetaminophen 3 times a day. I had never touched an opiate before in my life. What a relief! I was so happy I could cry, just for a few hours of pain relief.  

I got a second opinion from another neurologist, who ordered more imaging and blood tests. The images came back as they have in the past, but the blood tests also showed there was severe inflammation – a possible sign of autoimmune disease. So off to rheumatology I go. 

After another 5-month wait for an appointment, the rheumatologist orders more blood tests and an in-depth panel for autoimmune disease. Eight of those tests come back elevated and 4 of them are so high they’re alarming. I think to myself, “This may be terrible news or it may be good news. Either way, I’m finally getting a diagnosis.” 

Not even close. I get all these test results sent to me in an app, with a message from the doctor saying everything “looks fine.” He suggests aspirin and ibuprofen, and that I get off the hydrocodone.  

I lost my temper at that point. How dare you insinuate I’m drug seeking! Like I didn’t try every other option first. All those needles driven into my spine, the steroids, and off-label antidepressants. The months of physical therapy, chiropractic and emotional therapy, all before finally resorting to actual pain medication. 

Some of these doctors and pharmacists with their discriminatory attitudes and actions are disgusting. If it was about the drugs, I’d drive 10 minutes into town and buy them at a fraction of the price I pay at the pharmacy.  

This whole ordeal between deductibles and loss of wages has easily cost me over $100,000. I could have done so much with that money. My wife would have her student debt paid off by now. Instead, it all goes into the for-profit healthcare system. We’re not patients, we’re profits.  

Being on opioid medication now for 2 years, I cannot function without them. Without my pain medication, I feel like someone with industrial grade tools is trying to physically remove my head from my neck. 

CVS is a nightmare and the other pharmacies aren’t any better. They give you that look when you walk in or call to check on a prescription: “Oh, it’s you again. We spoke last month. You’re too early. We know why you people do that.” 

Excuse me, but I’m allowed to pick up my medication the day before I am out, so that I have medication available when I wake up the next day. So that I don’t have call you at 9am when you get in and then have to wait until 3 in the afternoon to pick it up. 

For a while, CVS was taking GoodRx coupons, which cut my insurance price in half. Recently, they told me there’s a new state law that prescription coupons were no longer valid for opioids. I checked with the state and no such law exists. The pharmacist does have the right to turn coupons away, but they flat out lied to me and said it was someone else making them do it.   

The number of days I’ve gone into withdrawal with brutal pain I wouldn’t wish on my worst enemy. All because CVS can’t find the prior authorization or they don’t tell me they are out of stock until I’m at the window to pick it up. Or some other excuse they can drum up. Just so they don’t have to give this “junkie” his drugs. It’s sickening.   

Now, all of a sudden, I can’t get hydrocodone of any dosage at any pharmacy within 50 miles of me. And none of them know when it’ll be back in stock. I found one pharmacy that had a three-week supply of hydrocodone, but by the time I got it called in and got there they said they only had two weeks supply for me because another patient needed a week.  

I’m officially up shirts creek without a paddle and don’t know what to do. I’m in the most pain I’ve ever felt in my life. It is 24/7 and unrelenting. It’s destroying my life, my marriage, my chance at children, my business, and my finances. I get sent from one specialist to another, and at each stop on the merry-go-round they extract $5 to $10 thousand from me in out-of-pocket tests.   

I’m not sure how much longer I can take it.  

Christopher Matthews is a pseudonym for the author, who asked that his full name not be used. He is 35 years old and played 3 years of professional soccer after graduating from college.

Do you have a “My Story” to share? Pain News Network invites other readers to share their experiences about living with pain and treating it.

Send your stories to editor@painnewsnetwork.org.

How Inflammation Can Lead to Chronic Pain

By Drs. Prakash Nagarkatti and Mitzi Nagarkatti, University of South Carolina

When your body fights off an infection, you develop a fever. If you have arthritis, your joints will hurt. If a bee stings your hand, your hand will swell up and become stiff. These are all manifestations of inflammation occurring in the body.

We are two immunologists who study how the immune system reacts during infections, vaccination and autoimmune diseases where the body starts attacking itself.

While inflammation is commonly associated with the pain of an injury or the many diseases it can cause, it is an important part of the normal immune response. The problems arise when this normally helpful function overreacts or overstays its welcome.

Generally speaking, the term inflammation refers to all activities of the immune system that occur where the body is trying to fight off potential or real infections, clear toxic molecules or recover from physical injury. There are five classic physical signs of acute inflammation: heat, pain, redness, swelling and loss of function. Low-grade inflammation might not even produce noticeable symptoms, but the underlying cellular process is the same.

Take a bee sting, for example. The immune system is like a military unit with a wide range of tools in its arsenal. After sensing the toxins, bacteria and physical damage from the sting, the immune system deploys various types of immune cells to the site of the sting. These include T cells, B cells, macrophages and neutrophils, among other cells.

The B cells produce antibodies. Those antibodies can kill any bacteria in the wound and neutralize toxins from the sting. Macrophages and neutrophils engulf bacteria and destroy them. T cells don’t produce antibodies, but kill any virus-infected cell to prevent viral spread.

Collateral Damage

Additionally, these immune cells produce hundreds of types of molecules called cytokines – otherwise known as mediators – that help fight threats and repair harm to the body. But just like in a military attack, inflammation comes with collateral damage.

The mediators that help kill bacteria also kill some healthy cells. Other similar mediating molecules cause blood vessels to leak, leading to accumulation of fluid and influx of more immune cells.

This collateral damage is the reason you develop swelling, redness and pain around a bee sting or after getting a flu shot. Once the immune system clears an infection or foreign invader – whether the toxin in a bee sting or a chemical from the environment – different parts of the inflammatory response take over and help repair the damaged tissue.

After a few days, your body will neutralize the poison from the sting, eliminate any bacteria that got inside and heal any tissue that was harmed.

Inflammation is a double-edged sword. It is critical for fighting infections and repairing damaged tissue, but when inflammation occurs for the wrong reasons or becomes chronic, the damage it causes can be harmful.

Allergies, for example, develop when the immune system mistakenly recognizes innocuous substances – like peanuts or pollen – as dangerous. The harm can be minor, like itchy skin, or dangerous if someone’s throat closes up.

Chronic inflammation damages tissues over time and can lead to many noninfectious clinical disorders, including cardiovascular diseases, neurodegenerative disorders, obesity, diabetes and some types of cancers.

The immune system can sometimes mistake one’s own organs and tissues for invaders, leading to inflammation throughout the body or in specific areas. This self-targeted inflammation is what causes the symptoms of autoimmune diseases such as lupus and arthritis.

Another cause of chronic inflammation that researchers like us are currently studying is defects in the mechanisms that curtail inflammation after the body clears an infection.

While inflammation mostly plays out at a cellular level in the body, it is far from a simple mechanism that happens in isolation. Stress, diet and nutrition, as well as genetic and environmental factors, have all been shown to regulate inflammation in some way.

There is still a lot to be learned about what leads to harmful forms of inflammation, but a healthy diet and avoiding stress can go a long way toward helping maintain the delicate balance between a strong immune response and harmful chronic inflammation.

Prakash Nagarkatti, PhD, and Mitzi Nagarkatti, PhD, are Professors of Pathology, Microbiology and Immunology at the University of South Carolina. They receive funding from the National Science Foundation and the National Institutes of Health.

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

Newly Discovered Gut Bacteria Linked to Rheumatoid Arthritis

By Meagan Chriswell, University of Colorado Medicine

Rheumatoid arthritis affects 1 in 100 people worldwide. It causes inflamed, painful and swollen joints, often in the hands and wrists, and can lead to loss of joint function as well as chronic pain and joint deformities and damage. What causes this condition has been unknown.

In our recently published study, my colleagues and I found an important clue to a potential culprit behind this disease: the bacteria in your gut.

Rheumatoid arthritis is an autoimmune condition, meaning it develops when the body’s immune system starts to attack itself. Proteins called antibodies, which usually help fight off viruses and bacteria, begin to attack the joints instead.

The origins of the antibodies that cause rheumatoid arthritis have been an area of study for many years. Some research has shown that these antibodies can start forming at sites like the mouth, lung and intestines over 10 years before symptoms arise. But until now, it was unclear why researchers were finding these antibodies in these particular areas.

We wanted to investigate what could trigger the formation of these antibodies. Specifically, we wondered if bacteria in the microbiome, a community of microorganisms that live in the intestines, might be the ones activating the immune response that leads to rheumatoid arthritis.

Since microbes commonly live at the same sites as the antibodies driving rheumatoid arthritis, we hypothesized that these bacteria could be triggering the production of these antibodies. We reasoned that though these antibodies were meant to attack the bacteria, rheumatoid arthritis develops when they spread beyond the intestines to attack the joints.

First, we sought to identify the intestinal bacteria targeted by these antibodies. To do this, we exposed the bacteria in the feces of a subset of people at risk for developing rheumatoid arthritis to these antibodies, allowing us to isolate just the bacterial species that reacted and bound to the antibodies.

We found that one previously unknown species of bacteria was present in the intestines of around 20% of people who were either diagnosed with rheumatoid arthritis or produce the antibodies that cause the disease.

As a member of the Cherokee Nation of Oklahoma, I suggested we name this species Subdoligranulum didolesgii (“didolesgii” means arthritis or rheumatism in Cherokee) as a nod to the contributions that other Indigenous scholars have made to science as well as the fact that rheumatoid arthritis affects Indigenous people at a higher rate than other populations.

Subdoligranulum didolesgii has not been detected in the feces of healthy people before, and it is currently unknown how prevalent this bacteria is in the general population.

We also found that these bacteria can activate specialized immune cells called T cells in people with rheumatoid arthritis. T cells drive inflammatory responses in the body, and have been linked to the development of different autoimmune diseases.

These findings suggest that these gut bacteria may be activating the immune systems of people with rheumatoid arthritis. But instead of attacking the bacteria, their immune system attacks the joints.

Why This Bacteria?

It is still unknown why people with rheumatoid arthritis develop an immune response to Subdoligranulum didolesgii. But we think it may be the culprit when it comes to rheumatoid arthritis because this bacteria is found only in the intestines of people with rheumatoid arthritis, and not in the intestines of healthy people.

While many immune responses happen in the intestines, they are usually self-contained and do not spread to other areas of the body. However, we believe that a particularly strong intestinal immune response against Subdoligranulum didolesgii could allow antibodies to bypass the intestinal “firewall” and spread to the joints.

To confirm our hypothesis, we gave mice an oral dose of Subdoligranulum didolesgii and monitored their reaction. Within 14 days, the mice began to develop joint swelling and antibodies that attacked their joints.

My colleagues and I hope this research can shed light on the origins of rheumatoid arthritis. Our next goal is to discover how common these bacteria are in the general population and test whether the presence of these bacteria in the gut may lead to the development of rheumatoid arthritis in people.

It’s important to note that antibiotics are unlikely to be helpful treatment for the microbiomes of patients with rheumatoid arthritis. Although Subdoligranulum didolesgii may be triggering an autoimmune response for some people with rheumatoid arthritis, antibiotics eliminate both helpful and harmful bacteria in the gut. Additionally, removing the bacteria won’t necessarily stop the immune system from attacking the joints once it has started.

Nevertheless, we believe that these bacteria can be used as tools to develop treatments for rheumatoid arthritis and hopefully ways to prevent disease from happening in the first place.

Meagan Chriswell is a MD/PhD Candidate in Immunology at the University of Colorado Anschutz Medical Campus. She does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article.

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

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.

Pharmacies Turning Away Patients Seeking 4th Covid Shot

By Liz Szabo, Kaiser Health News

Patients with weakened immune systems — who are at high risk from covid-19 — say pharmacies are turning them away when they seek additional vaccine doses recommended by federal health officials.

Alyson Smith became eligible this month for a fourth vaccine dose because her medications leave her immunocompromised.

Although the Centers for Disease Control and Prevention encourages most adults to receive a total of three mRNA vaccines — two “primary” vaccinations and a booster — the agency now advises people with weak immune systems to receive three primary shots plus a booster, for a total of four doses.

Many people are confused about the difference between a primary vaccine series and a booster. A primary vaccine series helps people build antibodies to a new pathogen, while a booster combats waning immunity.

As Smith learned, many pharmacists are unaware that the CDC’s vaccine guidance has changed.

Smith booked her vaccine appointment online. But when she showed up at a Chicago-area Walgreens for the appointment Jan. 19, an employee told her the pharmacy chain wasn’t administering fourth doses to anyone.

Smith said she’s frustrated that vulnerable people are being forced to make multiple visits to crowded pharmacies and supermarkets, where many customers are unmasked.

“I feel for the pharmacists, because they’re overwhelmed like everyone else,” said Smith, 52. “But two years into the pandemic, there is a corporate responsibility to take action when the guidance comes down.”

In a written statement, Walgreens said it has administered thousands of fourth doses to immunocompromised people. “As vaccination guidelines continue to evolve, we make every effort to continuously update our pharmacy teams.”

(Update: In a conference call on January 26, the CDC told pharmacists that people with moderate to severe immune suppression are eligible for a 4th covid shot. About 7 million Americans can get the extra shot.)

Confusing Vaccine Guidance

The confusion stems from recent updates in vaccine advice for immunocompromised people, as well as a change in the interval between the end of a primary vaccine series and a booster.

• In August, the CDC began allowing immunocompromised people to receive a third dose of mRNA vaccine as part of their primary vaccination.

• In October, the CDC quietly updated its website to allow people with suppressed immune systems to receive a fourth shot as a booster.

• In January, the agency shortened the time that anyone must wait for a booster from six months to five.

People who received the one-dose Johnson & Johnson vaccine are eligible for a single booster, for a total of two shots, according to the CDC.

Given how often vaccine guidelines have been revised in recent months, some pharmacists have had a hard time keeping pace, said Mitchel Rothholz, chief of governance and state affiliates at the American Pharmacists Association. Pharmacy employees have coped with an ever-expanding workload but a deepening shortage of employees during the pandemic, he said.

“I don’t know any provider who wants to turn away a patient,” Rothholz said. “The CDC continues to make updates, and it’s becoming very difficult for providers at the grassroots level to keep up. I can understand why a pharmacist would say, ‘Corporate hasn’t given us the green light.’”

Confusion about who is eligible for a fourth shot “was inevitable, although I’m not saying it’s right or wrong,” he said.

Yet many patients and their doctors are frustrated.

If patients keep up with the latest guidelines, they ask, why can’t their pharmacy?

“It’s ridiculous,” said Dr. Dorry Segev, a transplant surgeon and researcher at Johns Hopkins University. “CDC makes it very clear that it’s allowed, and even people who print out the CDC guidance and take it to their pharmacies are being turned away.”

Charis Hill, 34, joined a chorus of immune-suppressed people venting their concerns on social media in recent days. When Hill tweeted Jan. 21 that Rite Aid should better educate its staff, the retailer tweeted back that day, saying, “We’re very sorry you didn’t have a great experience, Charis. Please check back with us early next month for more information regarding the fourth dose.”

In a written statement, Rite Aid said it continually educates its staff as CDC advice changes, and “is looking into the response that was provided to the customer on social media.”

Dr. Shikha Jain, an assistant professor of medicine at the University of Illinois Cancer Center in Chicago, said patients in rural areas often drive long distances to look for vaccines. One of her patients was “almost in tears” after being turned away. Jain tried to help by calling the pharmacy but was on hold so long that she had to hang up to see patients.

Jain said the CDC needs to do a better job educating doctors, pharmacists, and patients.

The CDC did not respond to a request for comment before publication.

Teresa Strahlman, 61, said she’s immunocompromised due to medications she takes for lupus, an autoimmune disease. But the Maryland woman said she didn’t realize she was eligible for a fourth dose until reading a KHN post on Facebook. “I had no idea, and I have a million doctors,” Strahlman said. “No one has said anything to me.”

The CDC estimates that 2.7% of adults — or 7 million people — are immunocompromised, a group that includes people with medical conditions that dampen their immune response, as well as those taking immune-suppressing drugs because of organ transplants, cancer, or autoimmune diseases.

Some immunocompromised people say that being turned away from a pharmacy is especially frustrating, given all that they have sacrificed during the pandemic.

Linda Rushing, 74, has given up attending church services in person, although she’s deeply religious, because of a weakened immune system that leaves her prone to a variety of infections.

Rushing made three visits to local pharmacies before finding someone to administer her fourth shot.

“It’s a tragedy to need help and not be able to get it,” said Rushing, of Rowlett, Texas, whose daughter and granddaughter are also immunocompromised. “I don’t want covid. I don’t want to give it to anybody, and I’m trying to do everything I can not to die from it.”

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

Surprise Discovery Could Lead to Vaccine for Rheumatoid Arthritis

By Pat Anson, Editor

A surprise discovery at a university laboratory could lead to a vaccine that can prevent rheumatoid arthritis, a chronic and incurable disease in which the body’s own immune system attacks joint tissues.

Researchers at The University of Toledo years were studying a protein called 14-3-3 zeta and its role in immune system pathologies. Previous studies have suggested the protein could be a possible trigger for rheumatoid arthritis (RA) and other autoimmune conditions that cause pain, inflammation and bone erosion.

But researchers found just the opposite. The team discovered that 14-3-3 zeta proteins may actually help prevent arthritis. When they removed the proteins through gene-editing technology, it caused severe early onset arthritis in laboratory animals.

Realizing that the proteins may be beneficial, the team developed an experimental vaccine using purified 14-3-3 zeta protein grown in a bacterial cell. They found the vaccine promoted a strong, immediate and long-lasting response in rodents that protected them from RA.

"Much to our happy surprise, the rheumatoid arthritis totally disappeared in animals that received a vaccine," said Ritu Chakravarti, PhD, an assistant professor at UToledo College of Medicine and lead author of research published in the journal Proceedings of the National Academy of Sciences. "Sometimes there is no better way than serendipity. We happened to hit a wrong result, but it turned out to be the best result. Those kinds of scientific discoveries are very important in this field."

In addition to suppressing the immune system response, the vaccine also significantly improved collagen content and bone quality — findings that suggests there could be long-term benefits following immunization.

Currently, rheumatoid arthritis is treated with steroids or medications that suppress the immune system, such as biologics and biosimilar drugs. While those therapies can alleviate pain and reduce inflammation, they can also make patients more vulnerable to infection and, in the case of biologics, are expensive. Biologic drugs can cost $25,000 a year.

“We have not made any really big discoveries toward treating or preventing rheumatoid arthritis in many years,” Chakravarti said. “Our approach is completely different. This is a vaccine-based strategy based on a novel target that we hope can treat or prevent rheumatoid arthritis. The potential here is huge.”

RA affects about 1.5 million Americans and about one percent of the global population. Women experience RA at a rate three times greater than men, have more severe symptoms and increased disability.

“In spite of its high prevalence, there is no cure and we don’t entirely know what brings it on. This is true of nearly all autoimmune diseases, which makes treating or preventing them so difficult,” said Chakravarti. “If we can successfully get this vaccine into the clinic, it would be revolutionary.”

Chakravarti and her colleagues have filed for a patent on their discovery and are seeking pharmaceutical industry partners to fund more research and preclinical trials.

How Long Haul Covid Alters the Immune System

By Liz Szabo, Kaiser Health News

There’s a reason soldiers go through basic training before heading into combat: Without careful instruction, green recruits armed with powerful weapons could be as dangerous to one another as to the enemy.

The immune system works much the same way. Immune cells, which protect the body from infections, need to be “educated” to recognize bad guys — and to hold their fire around civilians.

In some Covid-19 patients, this education may be cut short. Scientists say unprepared immune cells appear to be responding to the coronavirus with a devastating release of chemicals, inflicting damage that may endure long after the threat has been eliminated.

“If you have a brand-new virus and the virus is winning, the immune system may go into an ‘all hands on deck’ response,” said Dr. Nina Luning Prak, co-author of a January study on Covid and the immune system. “Things that are normally kept in close check are relaxed. The body may say, ‘Who cares? Give me all you’ve got.’”

While all viruses find ways to evade the body’s defenses, a growing field of research suggests that the coronavirus unhinges the immune system more profoundly than previously realized.

Some Covid survivors have developed serious autoimmune diseases, which occur when an overactive immune system attacks the patient, rather than the virus. Doctors in Italy first noticed a pattern in March 2020, when several Covid patients developed Guillain-Barré syndrome, in which the immune systems attacks nerves throughout the body, causing muscle weakness or paralysis.

As the pandemic has surged around the world, doctors have diagnosed patients with rare, immune-related bleeding disorders. Other patients have developed the opposite problem, suffering blood clots that can lead to stroke.

All these conditions can be triggered by “autoantibodies” — rogue antibodies that target the patient’s own proteins and cells. In a report published in October, researchers even labeled the coronavirus “the autoimmune virus.”

Although doctors are researching ways to overcome immune disorders in Covid patients, new treatments will take time to develop. Scientists are still trying to understand why some immune cells become hyperactive — and why some refuse to stand down when the battle is over.

Key immune players called “helper T cells” typically help antibodies mature. If the body is invaded by a pathogen, however, these T cells can switch jobs to hunt down viruses, acting more like “killer T cells,” which destroy infected cells. When an infection is over, helper T cells usually go back to their old jobs.

In some people with severe Covid, however, helper T cells don’t stand down when the infection is over, said James Heath, a professor and president of Seattle’s Institute for Systems Biology.

About 10% to 15% of hospitalized Covid patients Heath studied had high levels of these helper T cells, which were still looking for the enemy long after it had been eliminated. He’s now studying whether these overzealous T cells might inflict damage that leads to chronic illness or symptoms of autoimmune disease.

“These T cells are still there months later and they’re aggressive,” Heath said. “They’re on the hunt.”

Friendly Fire

Covid appears to confuse multiple parts of the immune system. In some patients, Covid triggers autoantibodies that target the immune system itself, leaving patients without a key defense against the coronavirus.

In October, a study published in Science led by Rockefeller University’s Jean-Laurent Casanova showed that about 10% of Covid patients become severely ill because they have antibodies against an immune system protein called interferon.

Disabling interferon is like knocking down a castle’s gate. Without these essential proteins, invading viruses can overwhelm the body and multiply wildly.

New research shows that the coronavirus may activate preexisting autoantibodies, as well as prompt the body to make new ones. In the January study, half of the hospitalized Covid patients had autoantibodies, compared with fewer than 15% of healthy people.

Other research has produced similar findings. In a study out in December, researchers found that hospitalized Covid patients harbored a diverse array of autoantibodies.

While some patients studied had antibodies against virus-fighting interferons, others had antibodies that targeted the brain, thyroid, blood vessels, central nervous system, platelets, kidneys, heart and liver, said Dr. Aaron Ring, assistant professor of immunology at Yale School of Medicine.

Similarities With Lupus

Some patients had antibodies associated with lupus, a chronic autoimmune disorder that can cause pain and inflammation in any part of the body. Covid patients rife with autoantibodies tended to have the severest disease, said Ring, who was surprised at the level of autoantibodies in some patients.

“They were comparable or even worse than lupus,” Ring said.

Researchers would like to know if lingering autoantibodies contribute to the symptoms of “long Covid,” which afflicts one-third of covid survivors up to nine months after infection, according to a new study in JAMA Network Open.

“Long haulers” suffer from a wide range of symptoms, including debilitating fatigue, shortness of breath, cough, chest pain and joint pain. Other patients experience depression, muscle pain, headaches, intermittent fevers, heart palpitations and problems with concentration and memory, known as brain fog.

Less commonly, some patients develop an inflammation of the heart muscle, abnormalities in their lung function, kidney issues, rashes, hair loss, smell and taste problems, sleep issues and anxiety.

The National Institutes of Health has announced a four-year initiative to better understand long Covid, using $1.15 billion allocated by Congress.

Ring said he’d like to study patients over time to see if specific symptoms might be explained by lingering autoantibodies.

“We need to look at the same patients a half-year later and see which antibodies they do or don’t have,” he said. If autoantibodies are to blame for long Covid, they could “represent an unfortunate legacy after the virus is gone.”

Kaiser Health News is a nonprofit news service covering health issues. It is not affiliated with Kaiser Permanente.

Latina and Asian Women at Significantly Higher Risk from Lupus

By Pat Anson, PNN Editor

Asians and Latinos diagnosed with systemic lupus erythematosus (SLE) are significantly more likely to die from the disease than other racial groups, according to a new analysis by the Centers for Disease Control and Prevention. The CDC set up half dozen state registries over a decade ago to help track the illness.

SLE is the most common form of lupus, a condition in which the body's immune system attacks its own healthy tissues, especially joints and skin, causing flare-ups of pain and fatigue that keep nearly half of adult patients from working.

In an effort to better understand why the disease disproportionately affects women and people of color, CDC researchers analyzed a database of over 800 SLE patients in San Francisco from 2007 to 2017. About 90 percent of them were female. Mortality rates were highest in racial and ethnic minorities who died during the study period,

“Asian females with SLE were four times more likely to die than were Asian females without SLE in the general San Francisco County population, and Hispanic/Latina females with SLE were six times more likely to die than were persons in the corresponding general populations,” researchers reported. “Higher mortality within these populations might be the result of more severe outcomes and manifestations of SLE, as previously demonstrated, or possibly less access to care.”

The mean age at death for people with SLE was 62 years. On average, Black persons died 6.8 years earlier than White people with SLE, while people of Hispanic/Latino ethnicity died 9.5 years earlier.

A recent study published in the journal Arthritis and Rheumatology estimated that over 200,000 Americans suffer from SLE, a number that comes statistically close to officially reclassifying the illness as a rare disease. The Rare Diseases Act of 2002 classifies conditions as rare when they affect 200,000 or fewer Americans. Until now, SLE disease estimates were larger but unverified.

“Our study potentially redefines systemic lupus erythematosus as a rare disease in the United States and lays the groundwork for where we need to focus our efforts to reduce the burden of this disease on Americans,” said lead investigator and rheumatologist Peter Izmirly, MD, an associate professor in the Department of Medicine at NYU Langone Health.

Rare-disease classification could, according to Izmirly, significantly improve efforts to study and treat SLE by reducing the number of participants needed for clinical trials.

Current treatments for lupus include steroids or other anti-inflammatory and immunosuppressing medications, including newer biologic drugs made from living cells.

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.