Discussion

From our literature review, there is a lack of knowledge regarding the MS experience for Indigenous Peoples in Canada. Most studies to date have been undertaken with administrative data, with minimal data on long-term follow-up. From the few studies published, the trends that have emerged are that the prevalence and incidence of MS in Indigenous Peoples are lower than the general population. However, the historically reported lower prevalence and incidence may at least in part be due to ascertainment bias and undercounting. Regardless, the prevalence has been increasing over time. Increasing prevalence may in part be accounted for by modest improvements in access to specialist care and diagnostic tests (e.g., MRI, biomarkers) over the past decade.

However, it is important to consider sociocultural/political factors that may arise from a history of colonialism and the displacement of Indigenous Peoples in Canada. Pediatric obesity is associated with an increased risk of MS, ^{Reference Gianfrancesco, Acuna and Shen23} and rates of being overweight and obesity are disproportionately higher among Indigenous youth in Canada. ²⁴ Higher rates of obesity among Indigenous youth are attributed to multiple factors, including food insecurity and a lack of access to traditional foods. ^{Reference Bhawra, Cooke, Hanning, Wilk and Gonneville25} Smoking is also associated with increased risk of developing MS as well as with increased disability scores, and rates of cigarette smoking are significantly higher among First Nations, Inuit and Métis populations in Canada. ²⁶ Lastly, increasing urbanization has been associated with rising rates of MS among otherwise genetically stable populations. ^{Reference Kotzamani, Panou and Mastorodemos27} As of 2021, approximately 61% of the Indigenous Peoples of Canada reside in urban communities. Urban migration of Indigenous Peoples in Canada is multifactorial, including sequelae of the residential school system, a lack of employment opportunities and access to healthcare and social services in home communities and disproportionate engagement with the justice system through incarceration and child welfare services, which result from anti-Indigenous racism and colonial practices in Canada. ^{Reference Akoodie28} An understanding of the factors that contribute to rising MS prevalence and severity among Indigenous Peoples in Canada underscores the importance of addressing social determinants of health in a culturally competent manner.

Increasing prevalence and aggressiveness of MS in those who self-identify as Indigenous Peoples in comparison to non-Indigenous White people appears to potentially be more aggressive. One clear limitation of the studies published to date is that four of the studies were published before 2004 when aquaporin-4 was discovered, in relation to NMOSD. Thus, those studies may have inadvertently included NMOSD rather than MS. ^{Reference Robers, Hurtubise, Roberts, Robinson, Schmidt and Amezcua29} There has also been a lack of separation of what the term Indigenous is referring to in most studies: First Nations, Inuit or Métis. Studies delineating the specific classification of Indigenous Peoples have only studied First Nations people with MS; there is no description of Inuit or Métis persons specifically with MS.

The most recent study looking at Indigenous Peoples with MS was published over six years ago, in 2018. Thus, any new changes in MS in the Indigenous population – diagnostically and with respect to clinical trajectory, also in relation to the COVID-19 pandemic – are unknown. Furthermore, when it comes to provincial and territory-specific data, only data from three provinces has been published: BC, Alberta and Manitoba. Given that these are not the regions where most Indigenous Peoples reside in the country, there is a large gap in our understanding of MS in the majority of the Indigenous population. In part, understanding MS in the Yukon, Northwest Territories and Nunavut is hampered by the fact that there are no permanent neurologists in these areas; small teams of neurologists from other places in Canada (e.g., Calgary) visit each of these regions every few months to provide care, some of whom are MS specialists, making continuity of care an issue. Even when neurologists are available, there is no nursing support nor allied health professionals available – critical parts of a multidisciplinary MS Clinic to help optimize care. ^{Reference Petrin, Marrie and Devonshire30} When possible, MS care takes place in capital cities in the territories. Thus, those who live more remotely need to take multiple means of transportation to get to the capital city, to get to the clinic – this can entail a combination of plane and bus travel, which can take several hours. With respect to prescribing disease-modifying therapies (DMTs), neurologists have been educating primary care providers/family physicians on how to prescribe and carry out monitoring lab work (S. Jarvis, personal communication, August 13, 2024). However, wait times to even be seen by a primary care provider are longer for Indigenous Peoples living in remote areas, ^{Reference Yangzom, Masoud and Hahmann31} and First Nations peoples living off reserve, Métis and Inuit have experienced difficulty being referred to a specialist. ³² Marrie and colleagues have created a case definition for MS that can be applied to persons with MS receiving primary care, ^{Reference Marrie, Kosowan, Taylor and Singer33} which could be very applicable in the case of Indigenous Peoples with MS that are mainly being managed by primary care providers. In that study, with application of their case definition, they identified 37 cases out of 13,673 persons, ^{Reference Marrie, Kosowan, Taylor and Singer33} though the percentage of those identifying as Indigenous was unknown. For MS care to become more readily available and streamlined for Indigenous Peoples in the territories, we need to be able to identify the population with MS – how many Indigenous Peoples have MS and the severity of their disease. Ideally, this would be followed by the establishment of a specialty MS Clinic, which would require the support of the local health authority in making neurologic care a priority.

For the data currently available, there are several unanswered questions in the areas of DMT use, biomarkers (serum, cerebrospinal fluid, MRI), long-term clinical trajectories and access to care, among others, for Indigenous Peoples living with MS. Knowledge of DMT use is particularly important given the known benefits of contemporary DMTs on the relapsing aspect of the disease. The status of DMT access in Indigenous Peoples living with MS is unknown. DMTs are prohibitively expensive for most patients, and the cost is typically covered by a combination of provincial drug plans and patient support programs through the pharmaceutical company creating the DMT. Enrolling patients in patient support programs and obtaining coverage for these medications require significant administrative support that is rarely available in rural or remote healthcare settings. As an attempt to mitigate access issues, First Nations and Inuit patients enrolled in the Non-insured Health Benefits program can access DMTs in all provinces under “Limited Use” codes rather than “Special Authorization,” as is required under all provincial drug plans. Determining the level of DMT use and subsequently improving DMT use is increasingly important with the advent of oral DMTs and high efficacy subcutaneous DMTs, as these may be easier to access, and infusion-based medications, which can be completed every 6 months in the cases of ocrelizumab, rituximab and ublituximab, are highly effective at reducing the chance of clinical relapse and/or new MRI activity.

Given the lack of data on Indigenous Peoples in Canada, one can look to Indigenous populations in other parts of the world including the USA, Australia, New Zealand and northern Europe. A systematic review of Indigenous persons with MS in the Americas ^{Reference Robers, Hurtubise, Roberts, Robinson, Schmidt and Amezcua29} described one administrative data-based study, finding the age-adjusted prevalence of MS in US Indigenous persons as 50.1 per 100,000, with a reported prevalence rate ratio of MS in Indigenous persons compared to White Americans as 0.39, ^{Reference Roberts and Erdei34} aligning with Canadian studies showing a lower prevalence of MS in Indigenous persons. In a contemporary study looking at the Indigenous populations of Australia and New Zealand, the New Zealand Māori population MS prevalence fell between that of Southeast Asian and European ancestry, while MS was found to be uncommon in the Australian Indigenous and Torres Strait Islander populations. ^{Reference Bukhari, Khalilidehkordi and Mason35} A study from 2014 looking specifically at the New Zealand/Aotearoa Māori population compared to the general New Zealand population did not find any differences between the groups regarding the percentage of persons with relapsing MS, EDSS or MS severity score. ^{Reference Pearson, Alla and Clarke36} Among the northern European Indigenous Sámi population in Norway, there is a much lower prevalence of MS compared to the rest of the Norwegian population, which was felt to be in part due to the reduced frequency of the HLA-DRB1*15-DQB1*06 haplotype in the Sámi population. ^{Reference Harbo, Utsi and Lorentzen37} Interestingly, Marrie and colleagues found that Indigenous Peoples in Manitoba were less likely to be HLA-DRB1*1501 positive. ^{Reference Marrie, Hall and Sadovnick17} Taken together, studies from across the world report a lower prevalence of MS among diverse Indigenous populations, which may partly relate to the lower frequency of MS genetic risk variants in these populations. However, clinical disease, biomarkers and long-term outcomes are very understudied in the Indigenous populations worldwide.

Research with Indigenous Peoples living with MS across Canada needs to be approached thoughtfully and with training in handling data sensitively and following principles of data sovereignty. One excellent resource is the First Nations Information Governance Centre (https://fnigc.ca/), with courses on ownership, control, access and possession (OCAP), a set of principles that should be applied when conducting research using First Nations’ data. At present, the First Nations Information Governance Centre does not cover the Inuit or Métis populations, but there is work ongoing by these groups. Upon developing an understanding of OCAP principles and data sovereignty, trust must be built with the diverse Indigenous communities, which can only occur with recognition of past and ongoing injustices. To this effect, the Canadian Medical Association delivered a public apology to Indigenous Peoples in September 2024 and published a formal apology document stating that they had systematically embedded and upheld anti-Indigenous racism in healthcare, creating an unsafe environment for Indigenous patients and communities. ³⁸ Ideally, apologies from other healthcare establishments are forthcoming that will be backed up with accountability and relationship building.

There is a pressing need for reconciliation and advocacy to improve Indigenous health and research. A dedicated MS advocacy and research group for Indigenous Peoples in Canada should include Indigenous Elders, health representatives, neurologists, primary care providers, researchers and policy experts to address disparities in diagnosis, treatment and access to culturally safe care. Despite the lower prevalence of MS, the group would focus on disease severity, social determinants of health and Indigenous-led research to improve health outcomes and equitable healthcare solutions. Such a group would collaborate directly with Indigenous communities, not only to foster meaningful inclusion in research but also to offer healthcare professionals diverse perspectives on wellness. It would provide education on Indigenous health within the medical profession, addressing the overreliance on Western frameworks of medicine and embracing alternative approaches to health and wellness. This knowledge translation would flow from healthcare professionals to Indigenous communities, and vice versa – needing to be reciprocal, with openness – to provide true translation and to make room for diverse interpretations. There is a need to consider knowledge and research in terms of the phenomena being studied but also to consider other elements surrounding this, thinking from a collective rather than individual perspective. ^{Reference Kovach39,Reference Wilson40} Lastly, to enhance care for Indigenous Peoples living with MS across Canada, clinics should adopt a multidisciplinary approach tailored to the unique needs of Indigenous Peoples. This includes integrating nurses, social workers and language interpreters trained in cultural safety, creating a supportive and controlled environment that fosters trust and ensures culturally responsive care for Indigenous patients.