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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.



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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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Toronto reports 2 more measles cases. Use our tool to check the spread in Canada – Toronto Star

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Canada has seen a concerning rise in measles cases in the first months of 2024.

By the third week of March, the country had already recorded more than three times the number of cases as all of last year. Canada had just 12 cases of measles in 2023, up from three in 2022.

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Cancer Awareness Month – Métis Nation of Alberta

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Cancer Awareness Month

Posted on: Apr 18, 2024

April is Cancer Awareness Month

As we recognize Cancer Awareness Month, we stand together to raise awareness, support those affected, advocate for prevention, early detection, and continued research towards a cure. Cancer is the leading cause of death for Métis women and the second leading cause of death for Métis men. The Otipemisiwak Métis Government of the Métis Nation Within Alberta is working hard to ensure that available supports for Métis Citizens battling cancer are culturally appropriate, comprehensive, and accessible by Métis Albertans at all stages of their cancer journey.

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Receiving a cancer diagnosis, whether for yourself or a loved one, can feel overwhelming, leaving you unsure of where to turn for support. In June, our government will be launching the Cancer Supports and Navigation Program which will further support Métis Albertans and their families experiencing cancer by connecting them to OMG-specific cancer resources, external resources, and providing navigation support through the health care system. This program will also include Métis-specific peer support groups for those affected by cancer.

With funding from the Canadian Partnership Against Cancer (CPAC) we have also developed the Métis Cancer Care Course to ensure that Métis Albertans have access to culturally safe and appropriate cancer services. This course is available to cancer care professionals across the country and provides an overview of who Métis people are, our culture, our approaches to health and wellbeing, our experiences with cancer care, and our cancer journey.

Together, we can make a difference in the fight against cancer and ensure equitable access to culturally safe and appropriate care for all Métis Albertans. Please click on the links below to learn more about the supports available for Métis Albertans, including our Compassionate Care: Cancer Transportation program.

I wish you all good health and happiness!

Bobbi Paul-Alook
Secretary of Health & Seniors

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Type 2 diabetes is not one-size-fits-all: Subtypes affect complications and treatment options – The Conversation

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You may have heard of Ozempic, the “miracle drug” for weight loss, but did you know that it was actually designed as a new treatment to manage diabetes? In Canada, diabetes affects approximately 10 per cent of the general population. Of those cases, 90 per cent have Type 2 diabetes.

This metabolic disorder is characterized by persistent high blood sugar levels, which can be accompanied by secondary health challenges, including a higher risk of stroke and kidney disease.

Locks and keys

In Type 2 diabetes, the body struggles to maintain blood sugar levels in an acceptable range. Every cell in the body needs sugar as an energy source, but too much sugar can be toxic to cells. This equilibrium needs to be tightly controlled and is regulated by a lock and key system.

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In the body’s attempt to manage blood sugar levels and ensure that cells receive the right amount of energy, the pancreatic hormone, insulin, functions like a key. Cells cover themselves with locks that respond perfectly to insulin keys to facilitate the entry of sugar into cells.

Unfortunately, this lock and key system doesn’t always perform as expected. The body can encounter difficulties producing an adequate number of insulin keys, and/or the locks can become stubborn and unresponsive to insulin.

All forms of diabetes share the challenge of high blood sugar levels; however, diabetes is not a singular condition; it exists as a spectrum. Although diabetes is broadly categorized into two main types, Type 1 and Type 2, each presents a diversity of subtypes, especially Type 2 diabetes.

These subtypes carry their own characteristics and risks, and do not respond uniformly to the same treatments.

To better serve people living with Type 2 diabetes, and to move away from a “one size fits all” approach, it is beneficial to understand which subtype of Type 2 diabetes a person lives with. When someone needs a blood transfusion, the medical team needs to know the patient’s blood type. It should be the same for diabetes so a tailored and effective game plan can be implemented.

This article explores four unique subtypes of Type 2 diabetes, shedding light on their causes, complications and some of their specific treatment avenues.

Severe insulin-deficient diabetes: We’re missing keys!

In severe insulin-deficient diabetes, beta cells limit production of the keys that unlock cells to allow entry of sugar from the blood.
(Lili Grieco-St-Pierre, Jennifer Bruin/Created with BioRender.com)

Insulin is produced by beta cells, which are found in the pancreas. In the severe insulin-deficient diabetes (SIDD) subtype, the key factories — the beta cells — are on strike. Ultimately, there are fewer keys in the body to unlock the cells and allow entry of sugar from the blood.

SIDD primarily affects younger, leaner individuals, and unfortunately, increases the risk of eye disease and blindness, among other complications. Why the beta cells go on strike remains largely unknown, but since there is an insulin deficiency, treatment often involves insulin injections.

Severe insulin-resistant diabetes: But it’s always locked!

A diagram of three closed locks and lots of keys

In severe insulin-resistant diabetes, the locks start ignoring the keys, triggering the beta cells to produce even more keys to compensate.
(Lili Grieco-St-Pierre, Jennifer Bruin/Created with BioRender.com)

In the severe insulin-resistant diabetes (SIRD) subtype, the locks are overstimulated and start ignoring the keys. As a result, the beta cells produce even more keys to compensate. This can be measured as high levels of insulin in the blood, also known as hyperinsulinemia.

This resistance to insulin is particularly prominent in individuals with higher body weight. Patients with SIRD have an increased risk of complications such as fatty liver disease. There are many treatment avenues for these patients but no consensus about the optimal approach; patients often require high doses of insulin.

Mild obesity-related diabetes: The locks are sticky!

Illustration of a lock and key

In mild obesity-related diabetes, the locks are ‘sticky,’ making it difficult for the keys to open the locks.
(Lili Grieco-St-Pierre, Jennifer Bruin/Created with BioRender.com)

Mild obesity-related (MOD) diabetes represents a nuanced aspect of Type 2 diabetes, often observed in individuals with higher body weight. Unlike more severe subtypes, MOD is characterized by a more measured response to insulin. The locks are “sticky,” so it is challenging for the key to click in place and open the lock. While MOD is connected to body weight, the comparatively less severe nature of MOD distinguishes it from other diabetes subtypes.

To minimize complications, treatment should include maintaining a healthy diet, managing body weight, and incorporating as much aerobic exercise as possible. This is where drugs like Ozempic can be prescribed to control the evolution of the disease, in part by managing body weight.

Mild age-related diabetes: I’m tired of controlling blood sugar!

Illustration of a lock and a beta cell

In people with mild age-related diabetes, both the locks and the beta cells that produce keys are tired, resulting in fewer keys and stubborn locks.
(Lili Grieco-St-Pierre, Jennifer Bruin/Created with BioRender.com)

Mild age-related diabetes (MARD) happens more often in older people and typically starts later in life. With time, the key factory is not as productive, and the locks become stubborn. People with MARD find it tricky to manage their blood sugar, but it usually doesn’t lead to severe complications.

Among the different subtypes of diabetes, MARD is the most common.

Unique locks, varied keys

While efforts have been made to classify diabetes subtypes, new subtypes are still being identified, making proper clinical assessment and treatment plans challenging.

In Canada, unique cases of Type 2 diabetes were identified in Indigenous children from Northern Manitoba and Northwestern Ontario by Dr. Heather Dean and colleagues in the 1980s and 90s. Despite initial skepticism from the scientific community, which typically associated Type 2 diabetes with adults rather than children, clinical teams persisted in identifying this as a distinct subtype of Type 2 diabetes, called childhood-onset Type 2 diabetes.




Read more:
Indigenous community research partnerships can help address health inequities


Childhood-onset Type 2 diabetes is on the rise across Canada, but disproportionately affects Indigenous youth. It is undoubtedly linked to the intergenerational trauma associated with colonization in these communities. While many factors are likely involved, recent studies have discovered that exposure of a fetus to Type 2 diabetes during pregnancy increases the risk that the baby will develop diabetes later in life.

Acknowledging this distinct subtype of Type 2 diabetes in First Nations communities has led to the implementation of a community-based health action plan aimed at addressing the unique challenges faced by Indigenous Peoples. It is hoped that partnered research between communities and researchers will continue to help us understand childhood-onset Type 2 diabetes and how to effectively prevent and treat it.

A mosaic of conditions

Illustration of different subtypes of Type 2 diabetes

Type 2 diabetes is a mosaic of conditions, each with its own characteristics.
(Lili Grieco-St-Pierre, Jennifer Bruin/Created with BioRender.com)

Type 2 diabetes is not uniform; it’s a mosaic of conditions, each with its own characteristics. Since diabetes presents so uniquely in every patient, even categorizing into subtypes does not guarantee how the disease will evolve. However, understanding these subtypes is a good starting point to help doctors create personalized plans for people living with the condition.

While Indigenous communities, lower-income households and individuals living with obesity already face a higher risk of developing Type 2 diabetes than the general population, tailored solutions may offer hope for better management. This emphasizes the urgent need for more precise assessments of diabetes subtypes to help customize therapeutic strategies and management strategies. This will improve care for all patients, including those from vulnerable and understudied populations.

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