Racial and Ethnic Disparities in the Incidence of Anti-NMDA Receptor Encephalitis.

OBJECTIVES: To estimate the incidence of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. METHODS: We conducted a retrospective cohort study of >10 million person-years of observation from members of Kaiser Permanente Southern California, 2011-2022. The electronic health record of individuals with text-string mention of NMDA and encephalitis were reviewed to identify persons who met diagnostic criteria for anti-NMDAR encephalitis. Age-standardized and sex-standardized incidences stratified by race and ethnicity were estimated according to the 2020 US Census population. RESULTS: We identified 70 patients who met diagnostic criteria for anti-NMDAR encephalitis. The median age at onset was 23.7 years (IQR = 14.2-31.0 years), and 45 (64%) were female patients. The age-standardized and sex-standardized incidence of anti-NMDAR encephalitis per 1 million person-years was significantly higher in Black (2.94, 95% CI 1.27-4.61), Hispanic (2.17, 95% CI 1.51-2.83), and Asian/Pacific Island persons (2.02, 95% CI 0.77-3.28) compared with White persons (0.40, 95% CI 0.08-0.72). Ovarian teratomas were found in 58.3% of Black female individuals and 10%-28.6% in other groups. DISCUSSION: Anti-NMDA receptor encephalitis disproportionately affected Black, Hispanic, or Asian/Pacific Island persons. Ovarian teratomas were a particularly common trigger in Black female individuals. Future research should seek to identify environmental and biological risk factors that disproportionately affect minoritized individuals residing in the United States.

Traumatic brain injury, race, ethnicity and cognition in newly diagnosed persons with multiple sclerosis.

We sought to determine whether a history of traumatic brain injury (TBI) could explain the lower symbol digit modalities test (SDMT) scores observed among newly diagnosed multiple sclerosis (MS) and control participants identifying as Black or Hispanic versus white in the MS Sunshine Study (n = 1172). 330 (29.2 %) participants reported a history of ≥1 TBI. Accounting for TBI did not explain the significant independent associations between having MS, being Black or Hispanic and lower SDMT. The pervasive effects of systemic racism in the United States remain the best explanation for the lower SDMT scores observed in Black and Hispanic participants.

Population-Based Estimates for the Prevalence of Multiple Sclerosis in the United States by Race, Ethnicity, Age, Sex, and Geographic Region.

Importance: Racial, ethnic, and geographic differences in multiple sclerosis (MS) are important factors to assess when determining the disease burden and allocating health care resources. Objective: To calculate the US prevalence of MS in Hispanic, non-Hispanic Black (hereafter referred to as Black), and non-Hispanic White individuals (hereafter referred to as White) stratified by age, sex, and region. Design, Setting, and Participants: A validated algorithm was applied to private, military, and public (Medicaid and Medicare) administrative health claims data sets to identify adult cases of MS between 2008 and 2010. Data analysis took place between 2019 and 2022. The 3-year cumulative prevalence overall was determined in each data set and stratified by age, sex, race, ethnicity, and geography. The insurance pools included 96 million persons from 2008 to 2010. Insurance and stratum-specific estimates were applied to the 2010 US Census data and the findings combined to calculate the 2010 prevalence of MS cumulated over 10 years. No exclusions were made if a person met the algorithm criteria. Main Outcomes and Measurements: Prevalence of MS per 100 000 US adults stratified by demographic group and geography. The 95% CIs were approximated using a binomial distribution. Results: A total of 744 781 persons 18 years and older were identified with MS with 564 426 cases (76%) in females and 180 355 (24%) in males. The median age group was 45 to 54 years, which included 229 216 individuals (31%), with 101 271 aged 18 to 24 years (14%), 158 997 aged 35 to 44 years (21%), 186 758 aged 55 to 64 years (25%), and 68 539 individuals (9%) who were 65 years or older. White individuals were the largest group, comprising 577 725 cases (77%), with 80 276 Black individuals (10%), 53 456 Hispanic individuals (7%), and 33 324 individuals (4%) in the non-Hispanic other category. The estimated 2010 prevalence of MS per 100 000 US adults cumulated over 10 years was 161.2 (95% CI, 159.8-162.5) for Hispanic individuals (regardless of race), 298.4 (95% CI, 296.4-300.5) for Black individuals, 374.8 (95% CI, 373.8-375.8) for White individuals, and 197.7 (95% CI, 195.6-199.9) for individuals from non-Hispanic other racial and ethnic groups. During the same time period, the female to male ratio was 2.9 overall. Age stratification in each of the racial and ethnic groups revealed the highest prevalence of MS in the 45- to 64-year-old age group, regardless of racial and ethnic classification. With each degree of latitude, MS prevalence increased by 16.3 cases per 100 000 (95% CI, 12.7-19.8; P < .001) in the unadjusted prevalence estimates, and 11.7 cases per 100 000 (95% CI, 7.4-16.1; P < .001) in the direct adjusted estimates. The association of latitude with prevalence was strongest in women, Black individuals, and older individuals. Conclusions and Relevance: This study found that White individuals had the highest MS prevalence followed by Black individuals, individuals from other non-Hispanic racial and ethnic groups, and Hispanic individuals. Inconsistent racial and ethnic classifications created heterogeneity within groups. In the United States, MS affects diverse racial and ethnic groups. Prevalence of MS increases significantly and nonuniformly with latitude in the United States, even when adjusted for race, ethnicity, age, and sex. These findings are important for clinicians, researchers, and policy makers.

Decreasing Multiple Sclerosis Treatment Expenditures and Improving Quality at the Health System Level.

OBJECTIVE: This study was undertaken to evaluate a multicomponent health system intervention designed to reduce escalating disease-modifying treatment (DMT) expenditures and improve multiple sclerosis (MS) outcomes by increasing use of preferred formulary and highly effective DMTs (HETs). METHODS: We conducted a trend study of treatment utilization and expenditure outcomes prior to (2009-2011) and during (2012-2018) MS Treatment Optimization Program (MSTOP) implementation in Kaiser Permanente Southern California (KPSC) compared to a Kaiser Permanente region of similar size. Annual relapse rates (ARRs) were obtained from KPSC's electronic health records. RESULTS: Adherence to preferred formulary DMTs increased from 25.4% in 2011 to 72.2% in 2017 following MSTOP implementation in KPSC and 22.1% to 43.8%, respectively, in the comparator. KPSC's annual DMT expenditures in 2018 were less than in 2011 despite an 11.3% increase in DMT-treated members. The decline in average per patient per year of treatment expenditures from a peak of $43.1 K in 2014 to $26.3 K in 2018 in KPSC was greater than the comparator, which peaked at $52.1 K and declined to $40.0 K in 2018. Over the 7 years following initiation of MSTOP, cumulative MS DMT expenditures were $161.6 million less than the comparator. HET use increased to 62.5% of per patient treatment-years versus 32.4% in the comparator. This corresponded to a 69% decline in adjusted ARR (95% confidence interval = 64.1-73.2%; p < 0.0001) among DMT-treated patients in KPSC. INTERPRETATION: A novel, expert-led health system intervention reduced MS DMT expenditures despite rising prices while simultaneously reducing MS relapse rates. Our focus on health system progress toward meaningful, measurable targets could serve as a model to improve quality and affordability of MS care in other settings. ANN NEUROL 2022;92:164-172.

Health Disparities, Inequities, and Social Determinants of Health in Multiple Sclerosis and Related Disorders in the US: A Review.

Importance: There is empirical evidence that social determinants of health (SDOH) impact health outcomes in Black and Hispanic and Latinx individuals in the US. Recently, SDOH have risen to the top as essential intervention targets that could help alleviate racial and ethnic disparities. Neuromyelitis optica spectrum disorder (NMOSD) disproportionately affects Black individuals, and multiple sclerosis (MS) has seen a recent shift in select racial groups. It is unclear to what degree SDOH have been investigated and contribute to racial and ethnic health disparities and inequities. Observations: This narrative review provides a contemporary synthesis of SDOH associated with racial and ethnic health disparities and inequities in MS, NMOSD, and other autoimmune disorders, such as myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease. These immune-mediated neurological diseases were chosen for their capacity to be a high burden to society and because of complementary SDOH-associated challenges among minority populations. A paucity of research addressing inequities and the role of SDOH in MS and NMOSD was noted despite findings that Black individuals have a higher risk of developing MS or NMOSD and associated mortality compared with White individuals. Greater health disparities were also found for those with lower income and education, lower health literacy, and negative illness perceptions in MS. No studies in MOG-Ab disorders were found. Conclusions and Relevance: Increased efforts are needed to better understand the role of SDOH in racial and ethnic health disparities and inequities in MS, NMOSD, and emerging autoimmune disorders. This includes developing research frameworks aimed at understanding the magnitude and interrelationships of SDOH to better develop system-based multilevel interventions across the spectrum of care for these neurological conditions.

Improving quality, affordability, and equity of multiple sclerosis care.

OBJECTIVE: The prevailing approaches to selecting multiple sclerosis (MS) disease modifying therapies (DMTs) have contributed to exponential increases in societal expenditures and out-of-pocket expenses, without compelling evidence of improved outcomes. Guidance is lacking regarding when and in whom the benefits of preventing MS-related disability likely outweighs the risks of highly effective DMTs (HET) and when it is appropriate to consider DMT costs. Our objective was to develop a standardized approach to improve the quality, affordability and equity of MS care. METHODS: MS experts partnered with health plan pharmacists to develop an ethical, risk-stratified, cost-sensitive treatment algorithm. We developed a risk-stratification schema to classify patients with relapsing forms of MS as high, intermediate or low risk of disability based on the best available evidence and, when the evidence was poor or lacking, by consensus. DMTs are grouped as highly, modestly or low/uncertain effectiveness and preferentially ranked within groups by safety based on pre-specified criteria. We reviewed FDA documents and the published literature. When efficacy and safety are equivalent, the lower cost DMT is preferred. RESULTS: Assignment to the high-risk group prompts treatment with preferred HETs early in the disease course. For persons in the intermediate- or low-risk groups with cost or health care access barriers, we incorporated induction therapy with an affordable B-cell depleting agent. Based on more favorable safety profiles, our preferred approach prioritizes use of rituximab and natalizumab among HETs and interferon-betas or glatiramer acetate among modestly effective agents. INTERPRETATION: The risk-stratified treatment approach we recommend provides clear, measurable guidance in whom and when to prescribe HETs, when to prioritize lower cost DMTs and how to accommodate persons with MS with cost or other barriers to DMT use. It can be adapted to other cost structures and updated quickly as new information emerges. We recommend that physician groups partner with health insurance plans to adapt our approach to their settings, particularly in the United States. Future studies are needed to resolve the considerable uncertainty about how much variability in prognosis specific risk factors explain.

The prevalence of MS in the United States: A population-based estimate using health claims data.

OBJECTIVE: To generate a national multiple sclerosis (MS) prevalence estimate for the United States by applying a validated algorithm to multiple administrative health claims (AHC) datasets. METHODS: A validated algorithm was applied to private, military, and public AHC datasets to identify adult cases of MS between 2008 and 2010. In each dataset, we determined the 3-year cumulative prevalence overall and stratified by age, sex, and census region. We applied insurance-specific and stratum-specific estimates to the 2010 US Census data and pooled the findings to calculate the 2010 prevalence of MS in the United States cumulated over 3 years. We also estimated the 2010 prevalence cumulated over 10 years using 2 models and extrapolated our estimate to 2017. RESULTS: The estimated 2010 prevalence of MS in the US adult population cumulated over 10 years was 309.2 per 100,000 (95% confidence interval [CI] 308.1-310.1), representing 727,344 cases. During the same time period, the MS prevalence was 450.1 per 100,000 (95% CI 448.1-451.6) for women and 159.7 (95% CI 158.7-160.6) for men (female:male ratio 2.8). The estimated 2010 prevalence of MS was highest in the 55- to 64-year age group. A US north-south decreasing prevalence gradient was identified. The estimated MS prevalence is also presented for 2017. CONCLUSION: The estimated US national MS prevalence for 2010 is the highest reported to date and provides evidence that the north-south gradient persists. Our rigorous algorithm-based approach to estimating prevalence is efficient and has the potential to be used for other chronic neurologic conditions.

Incidence of multiple sclerosis in multiple racial and ethnic groups.

OBJECTIVE: To determine whether the incidence of multiple sclerosis (MS) varies by race/ethnicity in a multiethnic, population-based cohort. METHODS: We conducted a retrospective cohort study of more than 9 million person-years of observation from the multiethnic, community-dwelling members of Kaiser Permanente Southern California health plan from January 1, 2008 to December 31, 2010. Incidence of MS and risk ratios comparing incidence rates between racial/ethnic groups were calculated using Poisson regression. RESULTS: We identified 496 patients newly diagnosed with MS who met McDonald criteria. The average age at diagnosis was 41.6 years (range 8.6-78.3 years) and 70.2% were women. The female preponderance was more pronounced among black (79.3%) than white, Hispanic, and Asian individuals with MS (67.8%, 68.1%, and 69.2%, respectively; p = 0.03). The incidence of MS was higher in blacks (10.2, 95% confidence interval [CI] 8.4-12.4; p < 0.0001) and lower in Hispanics (2.9, 95% CI 2.4-3.5; p < 0.0001) and Asians (1.4, 95% CI 0.7-2.4; p < 0.0001) than whites (6.9, 95% CI 6.1-7.8). Black women had a higher risk of MS (risk ratio 1.59, 95% CI 1.27-1.99; p = 0.0005) whereas black men had a similar risk of MS (risk ratio 1.04, 95% CI = 0.67-1.57) compared with whites. CONCLUSIONS: Our findings do not support the widely accepted assertion that blacks have a lower risk of MS than whites. A possible explanation for our findings is that people with darker skin tones have lower vitamin D levels and thereby an increased risk of MS, but this would not explain why Hispanics and Asians have a lower risk of MS than whites or why the higher risk of MS among blacks was found only among women.

Sociodemographic characteristics of members of a large, integrated health care system: comparison with US Census Bureau data.

BACKGROUND: Data from the memberships of large, integrated health care systems can be valuable for clinical, epidemiologic, and health services research, but a potential selection bias may threaten the inference to the population of interest. METHODS: We reviewed administrative records of members of Kaiser Permanente Southern California (KPSC) in 2000 and 2010, and we compared their sociodemographic characteristics with those of the underlying population in the coverage area on the basis of US Census Bureau data. RESULTS: We identified 3,328,579 KPSC members in 2000 and 3,357,959 KPSC members in 2010, representing approximately 16% of the population in the coverage area. The distribution of sex and age of KPSC members appeared to be similar to the census reference population in 2000 and 2010 except with a slightly higher proportion of 40 to 64 year olds. The proportion of Hispanics/Latinos was comparable between KPSC and the census reference population (37.5% vs 38.2%, respectively, in 2000 and 45.2% vs 43.3% in 2010). However, KPSC members included more blacks (14.9% vs 7.0% in 2000 and 10.8% vs 6.5% in 2010). Neighborhood educational levels and neighborhood household incomes were generally similar between KPSC members and the census reference population, but with a marginal underrepresentation of individuals with extremely low income and high education. CONCLUSIONS: The membership of KPSC reflects the socioeconomic diversity of the Southern California census population, suggesting that findings from this setting may provide valid inference for clinical, epidemiologic, and health services research.

Health plan administrative records versus birth certificate records: quality of race and ethnicity information in children.

BACKGROUND: To understand racial and ethnic disparities in health care utilization and their potential underlying causes, valid information on race and ethnicity is necessary. However, the validity of pediatric race and ethnicity information in administrative records from large integrated health care systems using electronic medical records is largely unknown. METHODS: Information on race and ethnicity of 325,810 children born between 1998-2008 was extracted from health plan administrative records and compared to birth certificate records. Positive predictive values (PPV) were calculated for correct classification of race and ethnicity in administrative records compared to birth certificate records. RESULTS: Misclassification of ethnicity and race in administrative records occurred in 23.1% and 33.6% children, respectively; the majority due to missing ethnicity (48.3%) and race (40.9%) information. Misclassification was most common in children of minority groups. PPV for White, Black, Asian/Pacific Islander, American Indian/Alaskan Native, multiple and other was 89.3%, 86.6%, 73.8%, 18.2%, 51.8% and 1.2%, respectively. PPV for Hispanic ethnicity was 95.6%. Racial and ethnic information improved with increasing number of medical visits. Subgroup analyses comparing racial classification between non-Hispanics and Hispanics showed White, Black and Asian race was more accurate among non-Hispanics than Hispanics. CONCLUSIONS: In children, race and ethnicity information from administrative records has significant limitations in accurately identifying small minority groups. These results suggest that the quality of racial information obtained from administrative records may benefit from additional supplementation by birth certificate data.