Multiple sclerosis (MS) has a strong racial and ethnic component and disproportionately affects whites of European background. Recent incidence reports suggest an increasing rate of MS among African Americans compared with whites. Despite this recent increase in MS in African Americans, Hispanics and Asians are significantly less likely to develop MS than whites of European ancestry. MS-specific mortality trends demonstrate distinctive disparities by race/ethnicity and age, suggesting that there is an unequal burden of disease. Inequalities in health along with differences in clinical characteristics that may be genetic, environmental, and social in origin may be contributing to disease variability and be suggestive of endophenotypes. The overarching goal of this review was to summarize the current understanding on the variability of disease that we observe in selected racial and ethnic populations: Hispanics and African Americans. Future challenges will be to unravel the genetic, environmental, and social determinants of the observed racial/ethnic disparities.

Background: Hispanics living with multiple sclerosis (MS) in the United States are not well defined. Objective: To describe the clinical characteristics of MS among Hispanic Whites (HW) in Southern California with those of non-Hispanic Whites (NHW). Methods: We performed a medical chart review to identify all cases of HW with MS (n = 125) who were treated at our institution during a 1-year period. We also identified cases of NHW with MS (100 NHW) treated at those clinics. All HW patients were interviewed to ascertain ancestry including detailed migration history. Disease progression was assessed by ambulatory disability and defined as Expanded Disability Status Scale (EDSS) score ≥6. Results: Compared with NHW, HW were more likely to have a relapsing–remitting form of MS and a younger age of onset (28.4 ± 0.97 years) with presenting symptoms of optic neuritis and transverse myelitis. However, overall ambulatory disability did not differ between HW and NHW. Migration to the US at age >15 years was associated with increased risk of disability in HW. Conclusions: HW living in the USA may be at risk of developing MS at an earlier age compared with NHW. Migration history can play an important role in the management of HW with MS.

Background: Demographic characteristics, social determinants of health (SDoH), health inequities, and health disparities substantially influence the general and disease-specific health outcomes of people with multiple sclerosis (MS). Participants in clinical trials do not represent all people with MS treated in practice. Objective: To provide recommendations for enhancing diversity and inclusion in clinical trials in MS. Methods: We held an international workshop under the Auspices of the International Advisory Committee on Clinical Trials in MS (the “Committee”) to develop recommendations regarding diversity and inclusivity of participants of clinical trials in MS. Workshop attendees included members of the Committee as well as external participants. External participants were selected based on expertise in trials, SDoH, health equity and regulatory science, and diversity with respect to gender, race, ethnicity, and geography. Results: Recommendations include use of diversity plans, community engagement and education, cultural competency training, biologically justified rather than templated eligibility criteria, adaptive designs that allow broadening of eligibility criteria over the course of a trial, and logistical and practical adjustments to reduce study participant burden. Investigators should report demographic and SDoH characteristics of participants. Conclusion: These recommendations provide sponsors and investigators with methods of improving diversity and inclusivity of clinical trial populations in MS.

Substantial progress has been made toward unraveling the genetic architecture of multiple sclerosis (MS) within populations of European ancestry, but few genetic studies have focused on Hispanic and African American populations within the United States. We sought to test the relevance of common European MS risk variants outside of the major histocompatibility complex (n = 200) within these populations. Genotype data were available on 2652 Hispanics (1298 with MS, 1354 controls) and 2435 African Americans (1298 with MS, 1137 controls). We conducted single variant, pathway, and cumulative genetic risk score analyses. We found less replication than statistical power suggested, particularly among African Americans. This could be due to limited correlation between the tested and causal variants within the sample or alternatively could indicate allelic and locus heterogeneity. Differences were observed between pathways enriched among the replicating versus all 200 variants. Although these differences should be examined in larger samples, a potential role exists for gene–environment or gene–gene interactions which alter phenotype differentially across racial and ethnic groups. Cumulative genetic risk scores were associated with MS within each study sample but showed limited diagnostic capability. These findings provide a framework for fine-mapping efforts in multi-ethnic populations of MS.