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TNF Inhibitors Linked to Increased Multiple Sclerosis Risk

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Anti-tumor necrosis factor alpha (TNF-alpha) inhibitors are associated with an increased risk for multiple sclerosis (MS), especially among patients with rheumatic disease (RD), new research shows.

When investigators combed medical databases in four Canadian provinces for information on patients with RD and irritable bowel disease (IBD) taking anti-TNF-alpha agents alongside matched controls in a prospective cohort study, they found an increased risk for MS in the RD patients.



Dr Antonio Aviña-Zubieta

Physicians shouldn’t hesitate to prescribe anti-TNF-alpha therapy for patients if they believe their patients can benefit from it, study investigator Antonio Aviña-Zubieta, MD, PhD, senior scientist at Arthritis Research Canada in Vancouver, British Columbia, told Medscape Medical News.

“To better provide a context of the magnitude of the risk, we would need to treat 2268 individuals with anti-TNF-alpha therapy in order to get one additional case of MS. This is considered a rare side effect [of anti-TNF therapy],” he said, adding that MS still occurred even in people who did not receive anti-TNF therapy.

“Nevertheless, we do not recommend anti-TNF in patients with MS or those with a family history of MS. The decision to take anti-TNF is best taken together by patient and health care provider,” said Aviña-Zubieta.

The study was published online October 28 in the journal Neurology.

Potential MS Link Investigated

Anti-TNF-alpha agents are often prescribed to stop inflammation for chronic immune disorders such as rheumatoid arthritis, inflammatory bowel disease (IBD), psoriasis, and ankylosing spondylitis. Prior research has raised suspicions of an increased risk of MS with use of anti-TNF-alpha agents in small samples.

Investigators accessed population-linked databases in the Canadian provinces of British Columbia, Alberta, Saskatchewan, and Manitoba, which contain information about physician visits, hospitalizations, demographic data, and medication in those provinces.

They mined the databases for information about patients diagnosed with RD and IBD between January 2000 and March 2018 and then determined new incident cases of MS in the two disease cohorts with at least three outpatient records related to MS, hospitalizations, or prescription claims for MS. Investigators could only obtain information about RD from databases in BC and Manitoba.

The anti-TNF-alpha drugs were dispensed in the 2 years prior to MS onset, and included adalimumab, certolizumab, etanercept, infliximab, and golimumab.

Each case of MS was matched with up to five control subjects of similar ages who did not receive anti-TNF-alpha agents, had similar RD or IBD illness duration, and the same approximate place of residence.

Investigators identified nearly 300,000 patients with RD. During follow-up, 462 of them developed MS (80% female, mean age 47) and were matched with 2300 controls with RD (60% female, mean age 47). They found that 18 people with RD and MS took an anti-TNF-alpha, vs 42 of the 2296 patients who had RD but not MS.

After adjusting for variables that could influence the risk of developing MS, the investigators discovered that people with RD who took an anti-TNF-alpha agent had a 105% increased risk of developing MS compared to people with RD who didn’t take an anti-TNF-alpha agent.

Aviña-Zubieta said it would be ill-advised for people with RD who have a family history of MS to use the anti-TNF agents, as there are other medications that could also be helpful.

Investigators noted a smaller increased risk for MS in the group with IBD, but the findings did not reach statistical significance.

There are several theories about how anti-TNF therapy might risk MS in certain patients. Aviña-Zubieta speculated that the therapy may increase reactivity from immune cells to myelin leading to a loss and malfunction of the affected areas. Additionally, “TNF blockage by this therapy may affect myelin repair. The possibility of higher risk of infections that could be linked to MS is possible too, but not proven,” he noted.

Study limitations included smaller sample sizes from Saskatchewan and Manitoba. Investigators also noted that MS prodrome periods can occur as much as 5 years before onset, so patients exhibiting early MS symptoms or MS prodrome who have not yet been diagnosed might be misdiagnosed as controls.

Context Is Important

Commenting on the study for Medscape Medical News, Amy Kunchok, MD, a staff neurologist at the Cleveland Clinic’s Mellen Center for Multiple Sclerosis, Cleveland, Ohio said context is important when interpreting the findings.



Dr Amy Kunchok

“Anti-TNF therapies are highly effective for many autoimmune disorders, as evidenced by numerous randomized controlled trials in rheumatological disorders and IBD,” said Kunchok, who was not involved in the study.

“As with any therapeutic decision, the physician needs to consider the medical needs of the patient and the risk–benefit scenario. In a patient with a preexisting MS diagnosis, we would generally not recommend these therapies, but instead suggest the treating specialist consider alternatives.

“However, in patients without prior inflammatory neurological disorders, these therapies may be safe and efficacious. There is more work needed to risk- stratify patients in terms of these rare inflammatory CNS events,” she added.

Neurology. Published online October 28, 2022. Abstract

The study was funded by the Canadian Institutes of Health Research. Aviña-Zubieta and Kunchok report no relevant financial relationships.

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Health Canada approves updated Moderna COVID-19 vaccine

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TORONTO – Health Canada has authorized Moderna’s updated COVID-19 vaccine that protects against currently circulating variants of the virus.

The mRNA vaccine, called Spikevax, has been reformulated to target the KP.2 subvariant of Omicron.

It will replace the previous version of the vaccine that was released a year ago, which targeted the XBB.1.5 subvariant of Omicron.

Health Canada recently asked provinces and territories to get rid of their older COVID-19 vaccines to ensure the most current vaccine will be used during this fall’s respiratory virus season.

Health Canada is also reviewing two other updated COVID-19 vaccines but has not yet authorized them.

They are Pfizer’s Comirnaty, which is also an mRNA vaccine, as well as Novavax’s protein-based vaccine.

This report by The Canadian Press was first published Sept. 17, 2024.

Canadian Press health coverage receives support through a partnership with the Canadian Medical Association. CP is solely responsible for this content.

The Canadian Press. All rights reserved.

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These people say they got listeria after drinking recalled plant-based milks

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TORONTO – Sanniah Jabeen holds a sonogram of the unborn baby she lost after contracting listeria last December. Beneath, it says “love at first sight.”

Jabeen says she believes she and her baby were poisoned by a listeria outbreak linked to some plant-based milks and wants answers. An investigation continues into the recall declared July 8 of several Silk and Great Value plant-based beverages.

“I don’t even have the words. I’m still processing that,” Jabeen says of her loss. She was 18 weeks pregnant when she went into preterm labour.

The first infection linked to the recall was traced back to August 2023. One year later on Aug. 12, 2024, the Public Health Agency of Canada said three people had died and 20 were infected.

The number of cases is likely much higher, says Lawrence Goodridge, Canada Research Chair in foodborne pathogen dynamics at the University of Guelph: “For every person known, generally speaking, there’s typically 20 to 25 or maybe 30 people that are unknown.”

The case count has remained unchanged over the last month, but the Public Health Agency of Canada says it won’t declare the outbreak over until early October because of listeria’s 70-day incubation period and the reporting delays that accompany it.

Danone Canada’s head of communications said in an email Wednesday that the company is still investigating the “root cause” of the outbreak, which has been linked to a production line at a Pickering, Ont., packaging facility.

Pregnant people, adults over 60, and those with weakened immune systems are most at risk of becoming sick with severe listeriosis. If the infection spreads to an unborn baby, Health Canada says it can cause miscarriage, stillbirth, premature birth or life-threatening illness in a newborn.

The Canadian Press spoke to 10 people, from the parents of a toddler to an 89-year-old senior, who say they became sick with listeria after drinking from cartons of plant-based milk stamped with the recalled product code. Here’s a look at some of their experiences.

Sanniah Jabeen, 32, Toronto

Jabeen says she regularly drank Silk oat and almond milk in smoothies while pregnant, and began vomiting seven times a day and shivering at night in December 2023. She had “the worst headache of (her) life” when she went to the emergency room on Dec. 15.

“I just wasn’t functioning like a normal human being,” Jabeen says.

Told she was dehydrated, Jabeen was given fluids and a blood test and sent home. Four days later, she returned to hospital.

“They told me that since you’re 18 weeks, there’s nothing you can do to save your baby,” says Jabeen, who moved to Toronto from Pakistan five years ago.

Jabeen later learned she had listeriosis and an autopsy revealed her baby was infected, too.

“It broke my heart to read that report because I was just imagining my baby drinking poisoned amniotic fluid inside of me. The womb is a place where your baby is supposed to be the safest,” Jabeen said.

Jabeen’s case is likely not included in PHAC’s count. Jabeen says she was called by Health Canada and asked what dairy and fresh produce she ate – foods more commonly associated with listeria – but not asked about plant-based beverages.

She’s pregnant again, and is due in several months. At first, she was scared to eat, not knowing what caused the infection during her last pregnancy.

“Ever since I learned about the almond, oat milk situation, I’ve been feeling a bit better knowing that it wasn’t something that I did. It was something else that caused it. It wasn’t my fault,” Jabeen said.

She’s since joined a proposed class action lawsuit launched by LPC Avocates against the manufacturers and sellers of Silk and Great Value plant-based beverages. The lawsuit has not yet been certified by a judge.

Natalie Grant and her seven year-old daughter, Bowmanville, Ont.

Natalie Grant says she was in a hospital waiting room when she saw a television news report about the recall. She wondered if the dark chocolate almond milk her daughter drank daily was contaminated.

She had brought the girl to hospital because she was vomiting every half hour, constantly on the toilet with diarrhea, and had severe pain in her abdomen.

“I’m definitely thinking that this is a pretty solid chance that she’s got listeria at this point because I knew she had all the symptoms,” Grant says of seeing the news report.

Once her daughter could hold fluids, they went home and Grant cross-checked the recalled product code – 7825 – with the one on her carton. They matched.

“I called the emerg and I said I’m pretty confident she’s been exposed,” Grant said. She was told to return to the hospital if her daughter’s symptoms worsened. An hour and a half later, her fever spiked, the vomiting returned, her face flushed and her energy plummeted.

Grant says they were sent to a hospital in Ajax, Ont. and stayed two weeks while her daughter received antibiotics four times a day until she was discharged July 23.

“Knowing that my little one was just so affected and how it affected us as a family alone, there’s a bitterness left behind,” Grant said. She’s also joined the proposed class action.

Thelma Feldman, 89, Toronto

Thelma Feldman says she regularly taught yoga to friends in her condo building before getting sickened by listeria on July 2. Now, she has a walker and her body aches. She has headaches and digestive problems.

“I’m kind of depressed,” she says.

“It’s caused me a lot of physical and emotional pain.”

Much of the early days of her illness are a blur. She knows she boarded an ambulance with profuse diarrhea on July 2 and spent five days at North York General Hospital. Afterwards, she remembers Health Canada officials entering her apartment and removing Silk almond milk from her fridge, and volunteers from a community organization giving her sponge baths.

“At my age, 89, I’m not a kid anymore and healing takes longer,” Feldman says.

“I don’t even feel like being with people. I just sit at home.”

Jasmine Jiles and three-year-old Max, Kahnawake Mohawk Territory, Que.

Jasmine Jiles says her three-year-old son Max came down with flu-like symptoms and cradled his ears in what she interpreted as a sign of pain, like the one pounding in her own head, around early July.

When Jiles heard about the recall soon after, she called Danone Canada, the plant-based milk manufacturer, to find out if their Silk coconut milk was in the contaminated batch. It was, she says.

“My son is very small, he’s very young, so I asked what we do in terms of overall monitoring and she said someone from the company would get in touch within 24 to 48 hours,” Jiles says from a First Nations reserve near Montreal.

“I never got a call back. I never got an email”

At home, her son’s fever broke after three days, but gas pains stuck with him, she says. It took a couple weeks for him to get back to normal.

“In hindsight, I should have taken him (to the hospital) but we just tried to see if we could nurse him at home because wait times are pretty extreme,” Jiles says, “and I don’t have child care at the moment.”

Joseph Desmond, 50, Sydney, N.S.

Joseph Desmond says he suffered a seizure and fell off his sofa on July 9. He went to the emergency room, where they ran an electroencephalogram (EEG) test, and then returned home. Within hours, he had a second seizure and went back to hospital.

His third seizure happened the next morning while walking to the nurse’s station.

In severe cases of listeriosis, bacteria can spread to the central nervous system and cause seizures, according to Health Canada.

“The last two months have really been a nightmare,” says Desmond, who has joined the proposed lawsuit.

When he returned home from the hospital, his daughter took a carton of Silk dark chocolate almond milk out of the fridge and asked if he had heard about the recall. By that point, Desmond says he was on his second two-litre carton after finishing the first in June.

“It was pretty scary. Terrifying. I honestly thought I was going to die.”

Cheryl McCombe, 63, Haliburton, Ont.

The morning after suffering a second episode of vomiting, feverish sweats and diarrhea in the middle of the night in early July, Cheryl McCombe scrolled through the news on her phone and came across the recall.

A few years earlier, McCombe says she started drinking plant-based milks because it seemed like a healthier choice to splash in her morning coffee. On June 30, she bought two cartons of Silk cashew almond milk.

“It was on the (recall) list. I thought, ‘Oh my God, I got listeria,’” McCombe says. She called her doctor’s office and visited an urgent care clinic hoping to get tested and confirm her suspicion, but she says, “I was basically shut down at the door.”

Public Health Ontario does not recommend listeria testing for infected individuals with mild symptoms unless they are at risk of developing severe illness, such as people who are immunocompromised, elderly, pregnant or newborn.

“No wonder they couldn’t connect the dots,” she adds, referencing that it took close to a year for public health officials to find the source of the outbreak.

“I am a woman in my 60s and sometimes these signs are of, you know, when you’re vomiting and things like that, it can be a sign in women of a bigger issue,” McCombe says. She was seeking confirmation that wasn’t the case.

Disappointed, with her stomach still feeling off, she says she decided to boost her gut health with probiotics. After a couple weeks she started to feel like herself.

But since then, McCombe says, “I’m back on Kawartha Dairy cream in my coffee.”

This report by The Canadian Press was first published Sept. 16, 2024.

Canadian Press health coverage receives support through a partnership with the Canadian Medical Association. CP is solely responsible for this content.

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B.C. mayors seek ‘immediate action’ from federal government on mental health crisis

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VANCOUVER – Mayors and other leaders from several British Columbia communities say the provincial and federal governments need to take “immediate action” to tackle mental health and public safety issues that have reached crisis levels.

Vancouver Mayor Ken Sim says it’s become “abundantly clear” that mental health and addiction issues and public safety have caused crises that are “gripping” Vancouver, and he and other politicians, First Nations leaders and law enforcement officials are pleading for federal and provincial help.

In a letter to Prime Minister Justin Trudeau and Premier David Eby, mayors say there are “three critical fronts” that require action including “mandatory care” for people with severe mental health and addiction issues.

The letter says senior governments also need to bring in “meaningful bail reform” for repeat offenders, and the federal government must improve policing at Metro Vancouver ports to stop illicit drugs from coming in and stolen vehicles from being exported.

Sim says the “current system” has failed British Columbians, and the number of people dealing with severe mental health and addiction issues due to lack of proper care has “reached a critical point.”

Vancouver Police Chief Adam Palmer says repeat violent offenders are too often released on bail due to a “revolving door of justice,” and a new approach is needed to deal with mentally ill people who “pose a serious and immediate danger to themselves and others.”

This report by The Canadian Press was first published Sept. 16, 2024

The Canadian Press. All rights reserved.

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