MS Minute: Disparities in Multiple Sclerosis: Incorporating Equity Into Clinical Care and Research

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system and presents with a wide spectrum of clinical variability among affected individuals. Although the cause of MS remains unknown, it has been proposed that genetic and environmental factors play significant roles in the incidence and prevalence of MS. Studies have shown genetic profiles associated with increased MS risk, and recent studies have shown exposure to Epstein-Barr virus in adolescent ages to be a potential risk factor for development of MS.¹ Disease modifying therapies (DMTs) can change the long-term outcomes of MS, reducing long-term disability, especially when started early in the disease course.²

MS historically has been thought of as a disease that affects primarily White individuals of northern European ancestry; however, recent studies have shown an increasing rate of MS among underrepresented populations.³ Furthermore, minority populations in the United States are reported to have a higher incidence of MS compared with people in their ancestral countries of origin.⁴ Underrepresented groups also may bear an unequal burden from the disease and may face more barriers to accessing quality care. There is a critical need for more awareness on the effects of MS in underrepresented demographic groups and more studies are needed to investigate differences in clinical outcomes and incidence of MS.

Clinical Outcomes in Diverse Demographic Groups

Studies have shown higher MS disability rates in people from underrepresented populations. Demographic background has emerged as a distinct factor that predicts long-term prognosis.⁴ Compared with White individuals, people with MS from racial or ethnic minorities may have distinct disease characteristics (Table). Studies reveal that Black individuals with MS are more likely to have higher lesion volumes and more rapid brain and retinal tissue loss as measured by MRI and optical coherence tomography compared with White individuals.⁵ Hispanic Americans have a higher frequency of optic neuritis and transverse myelitis than White Americans.^3,4 Hispanic Americans have been reported to develop MS at a younger age compared with White Americans.³ Black individuals with MS have been reported to have more severe disease at baseline with greater occurrence of multifocal presentation at the onset of disease.⁶ Differences in clinical outcomes often are confounded by socioeconomic factors. Hispanic and Black individuals often are overrepresented in groups that are socioeconomically disadvantaged, may face barriers to accessing quality health care, and are more likely to experience health disparities and racism than White individuals.^3,7

More studies are needed to improve understanding of the differences in clinical outcomes of MS within diverse populations. The contribution of factors such as genetics, social determinants of health, and the environment need better characterization in predicting long-term outcomes. In addition, more resources are needed to provide quality care to people with MS from underrepresented groups who are affected by adverse social determinants of health.

Differential Response to DMTs

Some studies have shown potential differential response to DMTs based on an individual’s background. For instance, Black individuals treated with B-cell–depleting DMTs have been reported to have faster B-cell repletion after infusion of anti-CD20 therapy.⁸ Interferon-Β has been shown to be less effective in Black individuals with MS in clinical trials.⁹ Subgroup analyses from clinical trials have shown that higher-efficacy DMTs, such as natalizumab (Tysabri; Biogen, Durham, NC), fingolimod (Gilenya; Novartis, Nuremberg, Germany), and ocrelizumab (Ocrevus; Genentech, Vacaville, CA) may provide more favorable clinical and radiographic outcomes in Black individuals with MS, although this evidence is limited because of low representation of minority populations in clinical trials.⁶

The reasons for possible differential response to DMTs among different demographic groups remain unclear, and more studies with diverse representation are needed to identify and characterize these factors. Treatment with effective DMTs is a critical factor in limiting long-term disability in people with MS; a differential response in specific demographic groups may lead to adverse outcomes if not understood and mitigated.

Prevalence and Incidence of MS in Underrepresented Populations

Recent studies have shown an increased incidence of MS over the past 5 decades. The rate of this increase has been more pronounced in minority populations, with incidence of MS being highest in Black women in some studies.^3,10,11 Recent MS prevalence studies have revealed a north-to-south gradient within the United States, with the highest prevalence rate reported to date.¹¹ Rising MS prevalence and incidence are partly attributable to improved longevity and better diagnostic testing in recent years. However, a higher incidence in women and northern latitudes persists, and significant disparities in clinical presentation, disease course, long-term disability, and prognosis among minority racial and ethnic populations have been reported.¹¹ Minority populations in the United States also have been reported to have a higher incidence of MS than do people in their ancestral countries of origin.⁴ This variance may be attributable in part to the effect of latitude on MS prevalence.

Despite evidence of rising rates of MS in underrepresented populations, the general perception of MS as a disorder primarily affecting White individuals has been persistent in the medical community and the public. The lack of awareness of MS in underrepresented groups may lead to delays in diagnosis, medical mistrust among members of underrepresented groups, poor allocations of resources to communities where these resources are acutely needed, and lack of research funding to investigate MS outcomes in diverse populations.

Gender Disparities: Are Men With Multiple Sclerosis Underserved?

With the current female to male preponderance in MS estimated to be 3:1, men with MS can be considered a minority in this context. Men with MS are susceptible to worse disability progression, often face unique clinical presentation (Table) and diagnostic challenges, and require specific treatment approaches.^13,14 Men are more likely to have progressive MS than relapsing forms of MS. In relapsing MS phenotypes, the initial presentation of MS in men has been reported to be more often pyramidal symptoms as opposed to optic neuritis, which is seen more commonly in women.¹⁴ Pyramidal symptom onset in MS is a potential risk factor for worsened disability and faster transition to secondary progressive MS. Imaging studies have reported higher gray matter atrophy in men, which could lead to worse disease progression.^15,16 Greater axonal loss, as suggested by higher number of T1 hypointense lesions (black holes), fewer gadolinium contrast-enhancing lesions, and greater thalamic atrophy and cortical thinning, also has been described in men.^15,16 These features generally are associated with adverse clinical outcomes and higher disability levels.

Further studies are needed to better understand the unique clinical features of MS in men, and contributors to poor outcomes need better characterization. From a clinical standpoint, proper monitoring and surveillance for progression are needed to optimize quality of life and limit long-term disability.

Socioeconomic Status and Social
Determinants of Health

Social determinants of health include economic stability, educational status, health literacy, access and utilization of health care, illness perceptions, and social and community context. These factors disproportionately affect individuals from minority groups, including the Black and Hispanic populations in the United States. Poor socioeconomic status and inadequate access to health care are factors that contribute to high clinical burden and adverse outcomes in underrepresented populations. Studies suggest that Black and Hispanic individuals with MS experience increased morbidity and are more likely affected by lower income and educational status, lower health literacy, and negative illness perceptions.¹²

Black and Hispanic individuals in the United States experience systemic and structural racism. They often encounter barriers to access of health care and in turn may have unequal well-being, negative illness perceptions, and distrust of the medical community.^12,17 A study that investigated perceptions of MS in Hispanic Americans found that among Hispanic individuals born outside the United States, men with lower income and lower educational status were more likely to perceive MS as a disease caused by strong emotions. Perceptions about MS having a supernatural component were more common in the Black compared with the White population.^12,18,19 Lack of insurance and accessibility to specialty services has been identified as a cause for delayed diagnosis. Reduced timely access to effective treatment options may exacerbate disparities in outcomes and prognosis in underrepresented populations.¹⁷

The COVID-19 pandemic has shed light on the effects of social determinants of health across all races and ethnicities. Factors such as loss of employment, reduced access to health care, limited proficiency in use of technology or online resources, lack of social support, mental health challenges, and reduced wellbeing were shown to affect people from underrepresented populations disproportionately.^17,20

Clinical Trials and Clinical Research

The factors contributing to demographic differences in the clinical presentation and outcomes of MS are not clearly understood and further clinical and epidemiologic research is needed to better understand these trends. The degree to which demographic clinical differences are attributable to genetic, environmental, or social factors is not clearly understood and needs further investigation. Better representation of all demographic groups in clinical trials is necessary in elucidating factors driving disparities in clinical outcomes. Studies that specifically investigate disease outcomes in minority groups also are needed because these populations will have smaller samples in most clinical studies and will be underpowered because of their minority status.

There is a paucity of clinical research in underrepresented demographic groups with MS. Individuals from minority populations are consistently underrepresented in clinical trials in the United States.^4,9 The reasons for low clinical research participation in minority subgroups are multifactorial, with contributary factors such as cultural beliefs, medical distrust, religious beliefs, illness perception, and socioeconomic factors.^4,12 Studies have shown that Black and Hispanic individuals are more likely to distrust the medical community and less likely to use preventative services compared with White individuals.^12,21 Infamous historic events such as the Tuskegee Syphilis Study have contributed to distrust within the Black community for participation in clinical research. More education and awareness about the benefits of clinical research is needed in underrepresented communities, along with provision of good-quality clinical care, social support, and community outreach.

Conclusion

MS is a complex disease that affects different demographic populations with great variability in clinical presentation, clinical course, and long-term prognosis. Biological, genetic, and social factors play important roles in the course and prognosis of MS. Greater awareness of the effect of MS in underrepresented communities and men is needed. More clinical and epidemiologic research is required to better understand the etiologic factors of and contributors to poor outcomes in different demographic groups.