Multiple Sclerosis in the Black Population of the United States

Historically, epidemiologic studies in the US have typically shown that multiple sclerosis (MS) most commonly affects young women, primarily of northern European ancestry. However, recent studies show the incidence of MS among people of self-identified African-American ancestry may equal or exceed that of other groups variously defined by the social constructs of race and ethnicity. These differences appears to be driven by a higher risk of MS for Black women compared with all groups.¹

Although Black people in the US are often underrepresented in clinical research, there are studies comparing manifestations of MS that show differences between Black and White populations with MS in disease severity, response to some disease-modifying therapies (DMTs), and access to specialty care. MS-specific mortality trends show that Black people with MS have the highest mortality rate among people age 55 or less and indicate the presence of distinct health care disparities on the basis of racial and ethnic identities.² Although genetic factors may play a role in these differences of disease presentation and severity, genetic predisposition does not account for the majority of MS risk. There is a continuing need to investigate how outcomes are modified by comorbid conditions and environmental and social determinants of health (eg, access to care and socioeconomic status). The relatively limited number of Black participants in studies contributes to a knowledge gap regarding best practices for care of this population.

Diagnosis and Disease Course

Individuals with African ancestry, particularly the West African diaspora, including the Americas and Caribbean, have relatively higher incidence and prevalence rates of neuromyelitis optica spectrum disorder (NMOSD) than people with primarily European ancestry. MS and NMOSD must be distinguished from each other because NMOSD is characterized by aggressive clinical relapses that may mimic fulminant exacerbations of MS, and some DMTs typically used for MS have been shown to worsen the clinical expression of NMOSD.³

Over the last 2 decades, multiple studies have shown that Black people with MS tend to have a more aggressive disease course. In a study of clinical characteristics of MS, Black individuals with MS had a higher likelihood of optic nerve and spinal cord involvement, leading to earlier disability. The median time between first symptom onset to diagnosis was 1 year in Black individuals compared with 2 years in White individuals.⁴ Black people with MS were less likely to have complete recoveries from attacks, had shorter times to second attacks, and more frequent relapses overall. Multifocal signs and symptoms were more common at initial presentation, which was associated with a poor prognosis.⁵ A faster transition from relapsing-remitting MS (RRMS) to secondary progressive MS (SPMS) was also noted in Black people with MS.⁶

Black people with MS are also more likely to have higher Expanded Disability Status Scale (EDSS) scores at diagnosis and follow-up, accelerated disease progression, cerebellar dysfunction, and a more frequent need for ambulatory assistance or wheelchair use.^7,8 Admission to nursing facilities can occur at a significantly earlier mean age, often because of motor impairment, with 25% of Black individuals in 1 study being totally dependent on assistance to complete activities of daily living. Other complications such as bowel and bladder incontinence, stage 4 pressure ulcers, and severe cognitive impairment appeared twice as likely to occur in Black individuals with MS.⁹ This consistent pattern of greater disability, unfortunately, may also be associated with earlier mortality.²

Black individuals with neurologic conditions are less likely to see an outpatient neurologist compared with White individuals and are more likely to be cared for in emergency departments or inpatient settings.¹⁰ Fortunately those who see a neurologist in the outpatient setting for MS care are quite likely to receive DMTs.⁵ It is critically important that people with MS are promptly referred for specialized care.

The more aggressive course of MS in Black people is also reflected in various imaging markers of disease severity. Optical coherence tomography (OCT) studies have revealed accelerated atrophy of the retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL).^11,12 Studies comparing changes in brain volume in MS demonstrate a significantly worse neurodegenerative pattern in Black individuals, with nearly double the rates of gray matter, white matter, and thalamic nuclear atrophy, as indicated by greater T1 and T2 lesion volumes.^13,14 An increased rate and extent of global cortical thinning has been noted despite controlling for EDSS. Differences in regional atrophy have also been reported.¹³ Lower magnetization transfer ratio (MTR) values within MS lesions and in normal-appearing gray and white matter have been observed in Black people with MS.¹⁴ There is also an association between gray matter volume loss and an elevated immunoglobulin G (IgG) index in Black people with MS, which has been linked to the observed faster disease progression.¹⁵ This raises the possibility of a more pronounced intrathecal humoral immune response in Black people that might lead to more aggressive central nervous system (CNS) injury that may have clinical implications regarding treatment choices.

Risk Factors

Considering the differences in disease expression between Black and White individuals with MS, multiple risk factors have been investigated. Admixture complicates the study of genetic risk factors within the population of Black individuals, and it appears that European genetic ancestry plays a role in the risk of MS. Studies show that Black individuals with the European haplotype HLA-DRB1*15:01 risk allele—the most commonly associated risk allele in MS—are 3 times more likely to develop MS compared with Black patients with the African haplotype.¹⁶ These same individuals were also twice as likely to have an earlier mean age of disease onset compared with Black people with MS who were not carriers of this allele. The African ancestry-specific HLA-DRB*15:03 correlates with a higher level of disability and a higher risk of requiring a cane. Genome-wide association studies (GWAS) investigating novel MS risk variants in Black people with MS found no genome-wide differences compared with White people with MS, suggesting a common genetic overlap in risk between the 2 populations.¹⁷

Because the risk of developing MS appears to increase with farther distance from the equator, environmental factors such as sun exposure and vitamin D levels are believed to play a role. In the US, Black people have higher rates of vitamin D deficiency, and this was thought to contribute to a higher risk of MS. The MS Sunshine study, however, found higher serum vitamin D levels were associated with lower risk of MS only in White individuals, and that higher lifetime sun exposure was associated with lower risk of MS regardless of racial or ethnic identity. This implies that the perceived benefit of higher vitamin D levels may not be caused by vitamin D itself but from immunomodulating effects of ultraviolet ray exposure.¹⁸

Health Disparities in Access to Treatment and Specialty Care

The underrepresentation of Black people in clinical trials makes interpreting evidence-based approaches to treatment and determining the true efficacy of common DMTs for this population challenging. In a study that compared treatment with different forms of interferon β-1a, Black participants had more relapses and were less likely to remain relapse-free and achieve no evidence of disease activity (NEDA). Although the results were not statistically significant (possibly underpowered by the small cohort of Black participants), Black individuals also developed more new lesions on MRI.¹⁹ In post hoc analysis of clinical trials of natalizumab, Black participants had a similar annualized relapse rate reduction as White participants, but decreases in clinical disability, seen overall, did not reach statistical significance in Black participants, which could again reflect a small sample size.²⁰ In a retrospective chart review of people with MS who were treated with conventional DMTs (eg, interferon β-1a or -1b, glatiramer acetate, and natalizumab), Black individuals had an increased median EDSS score difference, pointing to a greater disability progression over a shorter period and a poorer response to these DMTs.²¹ Considering that some studies hint at a key role of the humoral immune system in CNS injury, B-cell–depleting therapies might prove more promising in this population. Post hoc analysis of Black participants in clinical trials of ocrelizumab had efficacy outcomes consistent with the overall pooled trial population,²² although it is challenging to determine how these subgroup analyses translate to clinical practice considering the small number of Black participants.

In addition, health disparities related to socioeconomic factors increase the burden of MS. When studies control for socioeconomic status, the difference in disease severity in Black vs White individuals may be reduced.²³ People who are uninsured or underinsured often experience lapses in health care coverage and are also less likely to have access to MS care by neuroimmunology subspecialists with experience managing aggressive forms of the disease.²⁴ Consequently, these individuals are less likely to receive the most thorough diagnostic and treatment-related testing, limiting their access to DMTs and referrals to other specialists (eg, physical and occupational therapists, mental health specialists, ophthalmologists, and urologists).²⁵ Failure to impart adequate education about the expected disease course (MS natural history), treatment goals and options, and community resources results in unrealistic expectations or reluctance to initiate and adhere to treatment.²⁶ Furthermore, studies show Black people tend to utilize community-based resources less often.²⁷ When admitted to nursing facilities, Black individuals often have limited rehabilitation services despite their significantly poorer physical performance and cognitive function because reimbursement for these services may be inadequate or even nonexistent for underinsured or uninsured individuals.⁸ Finally, even when access to health care exists, mistrust of the medical establishment caused by historic abuses of power (eg, Tuskegee Syphilis Study, among others) may create barriers that, in turn, exacerbate the already existing disparities in disease severity.

Conclusions

The variety of clinical and radiologic features outlined in recent literature demonstrate an increased burden of MS-related disability for Black people with MS. There is an important need to substantially increase inclusion of Black participants and people from other historically minoritized groups in the US within clinical trials to assess the efficacy of treatments and establish more robust evidence-based standards of care (See Inclusive Research for Multiple Sclerosis). Furthermore, dissection of MS risk determinants—whether social, environmental, or genetic—will enable us to better explore the relationship between these factors and clinical outcomes. In clinical practice, neurologists serve critical roles in direct care, consultation, and education for both patients and medical colleagues in the management of MS care (including coordination with primary care, referrals to physical and occupational therapy, engagement with advocacy organizations, and referrals to specialists such as urology and ophthalmology). Demonstrating an understanding of and openly acknowledging the specific morbidity and mortality risks and circumstantial barriers facing Black people with MS may increase confidence that the neurologist is aware of the larger picture while delivering excellent care.