Neurology and therapy · 2025
Real-World Treatment Outcomes in Black, Hispanic, Asian, and White People with Multiple Sclerosis Treated with Fumarates in the USA.
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Woodson Sophia, Gettings Edward J, Guo Chu-Yueh, Klineova Sylvia, Lee Jong-Mi, Romero Rebecca S, Walker Aljoeson, Fong Kinyee, Mendoza Jason P, Belviso Nicholas, Bian Boyang, Lewin James B, Shankar Sai L
Аннотация
INTRODUCTION: Multiple sclerosis (MS) is a heterogeneous disease affecting a diverse population. Compared with white people with MS (PwMS), Black PwMS have more severe disease and higher incidence of MS, whereas Hispanic PwMS experience earlier onset disease; however, MS is not adequately studied in these groups. We compared the effectiveness of fumarates across Black, Hispanic, Asian, and white PwMS.
METHODS: This retrospective analysis using the Komodo Health database included PwMS. Patients with a claim for diroximel fumarate or dimethyl fumarate were followed from disease-modifying therapy (DMT) initiation to loss of follow-up or discontinuation. Outcomes included annualized relapse rate (ARR), time to post-index first relapse, healthcare resource use (HRU), healthcare costs (HCCs), and change in absolute lymphocyte counts (ALCs). Race/ethnicity was self-reported.
RESULTS: This study included 6800 PwMS (Black, n = 1241; Hispanic, n = 777; Asian, n = 132; white, n = 4650). The average exposure duration of fumarates was 449-559 days. Black PwMS had higher baseline disease burden versus white PwMS, were less likely to have commercial insurance plans, and were more likely to reside in a state with a higher poverty rate. ARRs (12-month pre-index to post-index) were significantly reduced across groups. The Kaplan-Meier estimated proportion of relapse-free patients at 2 years was similar across groups (Black, 77.0%; Hispanic, 75.4%; Asian, 81.7%; white, 80.5%). There was a smaller decline in ALC from month 0 to month 12 in Black PwMS versus other racial/ethnic groups.
CONCLUSION: Consistent with prior studies, these results demonstrate the effectiveness of fumarates across racial and ethnic MS subgroups. This is the largest analysis to date of the treatment effects of any individual class of DMT in Black and Hispanic PwMS. Infographic available for this article.
METHODS: This retrospective analysis using the Komodo Health database included PwMS. Patients with a claim for diroximel fumarate or dimethyl fumarate were followed from disease-modifying therapy (DMT) initiation to loss of follow-up or discontinuation. Outcomes included annualized relapse rate (ARR), time to post-index first relapse, healthcare resource use (HRU), healthcare costs (HCCs), and change in absolute lymphocyte counts (ALCs). Race/ethnicity was self-reported.
RESULTS: This study included 6800 PwMS (Black, n = 1241; Hispanic, n = 777; Asian, n = 132; white, n = 4650). The average exposure duration of fumarates was 449-559 days. Black PwMS had higher baseline disease burden versus white PwMS, were less likely to have commercial insurance plans, and were more likely to reside in a state with a higher poverty rate. ARRs (12-month pre-index to post-index) were significantly reduced across groups. The Kaplan-Meier estimated proportion of relapse-free patients at 2 years was similar across groups (Black, 77.0%; Hispanic, 75.4%; Asian, 81.7%; white, 80.5%). There was a smaller decline in ALC from month 0 to month 12 in Black PwMS versus other racial/ethnic groups.
CONCLUSION: Consistent with prior studies, these results demonstrate the effectiveness of fumarates across racial and ethnic MS subgroups. This is the largest analysis to date of the treatment effects of any individual class of DMT in Black and Hispanic PwMS. Infographic available for this article.
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Key Summary Points
Why carry out this study? Racial and ethnic minority people with multiple sclerosis (PwMS) have been reported to have a worse clinical course and disability outcomes than white PwMS, although multiple sclerosis (MS) is not adequately studied in these groups. To compare the real-world effectiveness of fumarates across Black, Hispanic, Asian, and white PwMS in the USA. What was learned from this study? Further confirmation that Black and Hispanic PwMS have higher disease burden at baseline. Fumarates were effective across all racial/ethnic groups in this real-world study. Black PwMS exhibited a smaller decline in absolute lymphocyte counts at 12 months post initiation of fumarates compared with Hispanic, Asian, and white PwMS.
Why carry out this study? Racial and ethnic minority people with multiple sclerosis (PwMS) have been reported to have a worse clinical course and disability outcomes than white PwMS, although multiple sclerosis (MS) is not adequately studied in these groups. To compare the real-world effectiveness of fumarates across Black, Hispanic, Asian, and white PwMS in the USA. What was learned from this study? Further confirmation that Black and Hispanic PwMS have higher disease burden at baseline. Fumarates were effective across all racial/ethnic groups in this real-world study. Black PwMS exhibited a smaller decline in absolute lymphocyte counts at 12 months post initiation of fumarates compared with Hispanic, Asian, and white PwMS.
Digital Features
This article is published with digital features, including an infographic, to facilitate understanding of the article. To view digital features for this article, go to 10.6084/m9.figshare.29047154.
Introduction
Multiple sclerosis (MS) is a complex and heterogeneous disease that affects a diverse population worldwide, with approximately 2.9 million people living with the disease globally, and nearly 1 million residing in the USA [ 1 ]. Of the total US population, 20% are Hispanic/Latino, 14% are Black/African American, and 6% are Asian [ 2 ]. It is crucial to study these patients from minority groups, as MS prevalence and progression can differ significantly across them. For example, Black individuals are reported to have a higher incidence of MS than white individuals, while Asian and Hispanic populations have lower incidences [ 3 ]. Moreover, Black people with MS (PwMS) tend to experience a more severe disease course, with more frequent relapses and faster disability progression compared with non-Black individuals [ 4 – 6 ]. Despite these disparities, there is limited research on MS in minority populations, primarily due to their underrepresentation in clinical trials [ 7 , 8 ]. In addition, only 14 out of 45 (31.1%) phase 3 trials in PwMS reported participants’ racial breakdowns, highlighting a significant data gap in these populations from a research perspective.
Dimethyl fumarate (DMF) and diroximel fumarate (DRF) are oral fumarate disease-modifying therapies (DMTs) with favorable efficacy and safety profiles that are approved for treating relapsing forms of MS [ 9 – 11 ]. As of 31 December 2023, approximately 607,448 patients have been treated with DMF (approx. 1.4 million person-years of exposure) [ 12 ], while approximately 44,297 patients have been treated with DRF (approx. 61,780 person-years of exposure) [ 13 ]. Previous studies have demonstrated the efficacy and safety of fumarates across patients from racial and ethnic minority groups with MS [ 14 – 17 ]. Recent findings from a post hoc analysis of the phase 3 EVOLVE-MS-1 study showed that DRF was an effective treatment option for Black PwMS, with similar outcomes to non-Black patient subgroups [ 18 ]. However, these studies were limited in number, often involved small patient populations, and did not adequately account for potential differences in MS presentation. In addition, social determinants of health (SDOH), which include socioeconomic status and access to healthcare, as well as the conditions into which people are born, live, work, and age, can affect MS outcomes and were not reported in these previous studies [ 19 ]. Disparities in healthcare access, lower health literacy, and biases in treatment decisions can contribute to worse MS outcomes in minority populations, suggesting that disease burden may not be fully explained by biological differences alone [ 19 , 20 ].
The underrepresentation of racial and ethnic minorities in clinical trials poses a significant challenge to understanding the differential impact of MS therapies across diverse populations. This study aims to address this gap by evaluating the real-world effectiveness of fumarates (both DMF and DRF) among Black, Hispanic, Asian, and white PwMS using the Komodo Health claims database. By including a substantial number of minority patients and considering factors such as state poverty level and type of insurance plan, this study seeks to provide a more comprehensive evaluation of how these therapies perform across different racial and ethnic groups.
We hypothesize that the effectiveness of fumarates will be consistent across these diverse populations. This research is crucial in filling the gaps left by previous studies, contributing valuable data to support more inclusive treatment strategies in MS care.
Methods
Study Design
This retrospective analysis used closed claims in the Komodo Health claims database to determine changes in efficacy outcomes after fumarates treatment in Black, Hispanic, Asian, and white PwMS. The Komodo Health database, a real-world, multipayer claims databases in the USA, integrates disparate sources of patient-level data to map longitudinal patient journeys. Komodo pulls de-identified, patient-level claims data from > 150 payers and provider data sources. Data on race and ethnicity was collected for patients who had an outpatient, inpatient, or emergency room (ER) visit and who chose to report race/ethnicity. Race and ethnicity were self-reported in one of two ways: either as a single designation (e.g., reporting as only Black or only Hispanic) or as separate fields, allowing for “Black” as race and “Hispanic” as ethnicity. In data reports where both race and ethnicity are provided, Komodo Health database used race over ethnicity. Alternately, if a patient provided ethnicity such as Hispanic as the first choice and race and ethnicity such as white, Hispanic as a second choice, the data were rank-ordered to choose ethnicity as the reportable data point. To ensure consistency, the Komodo Health database consolidates race and ethnicity data into one field [ 21 ]. The designations were (1) Black people, which included those who reported their race as Black or African American, (2) Hispanic people, which included those who reported their ethnicity as Hispanic or Latino, and (3) Asian people, which included those who reported their race as Asian or Pacific Islander (defined as persons having origins in any of the original peoples of the Far East, Southeast Asia, the Indian subcontinent, Hawaii, Guam, Samoa, or other Pacific Islands).
Patients
PwMS included in this study were 18–64 years old and had ≥ 1 claim for MS diagnosis (based on International Classification of Disease [ICD]-9 and ICD-10 diagnosis codes) from 01 January 2016 to 31 August 2022, and a claim for DMF (including TECFIDERA ® or generic DMF) or DRF (VUMERITY ® ) between 01 January 2017 and 31 May 2022. The index date was defined as the earliest date of the first fumarates claim (i.e., the first documented paid prescription fill date of fumarates treatment). Eligible patients also had continuous medical and pharmacy enrollment for 1 year prior to the index date (≤ 45-day gap) and ≥ 3 months continuous enrollment and continuous exposure to DMT after index date (≤ 45-day gap). Patients who switched from another oral or injectable DMT such as interferon-beta, glatiramer acetate, teriflunomide, fingolimod, ponesimod, siponimod, or cladribine to fumarates therapy were eligible for inclusion. Patients were excluded if they had multiple DMTs on the fumarates index date or had monoclonal antibody DMT at any time pre-index date.
PwMS were followed from index date to the end of study (31 May 2022), end of insurance eligibility, a gap in index DMT of > 45 days, or a switch from index DMT to another DMT, whichever occurred first.
Outcomes
The primary outcome was the change in annualized relapse rate (ARR) from 12 months pre-index to 12 months post-index. Relapses were defined as an MS-related inpatient claim with a primary diagnosis of MS (ICD 9/10 codes 340/G35) or an outpatient MS-related diagnosis plus a prescription claim for an intravenous (IV) steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid (≥ 500 mg/day prednisone or equivalent) ≤ 7 days after the outpatient visit [ 22 ]. Relapses that occurred within 30 days were considered as a single episode. Mild relapses that did not prompt a patient to interact with the healthcare system were not captured in claims data.
Secondary outcomes were the post-index ARR by racial strata versus white, time to first relapse post-index (up to month 24), absolute lymphocyte counts (ALCs) from baseline to 12 months post-index, and health and post-index MS-related costs. MS-related healthcare resource utilization (HRU) and healthcare costs (HCCs) were identified by claims with an associated MS diagnosis code of G35.
To be included in the ALC subgroup analyses, patients were required to have an ALC measurement at month 0 and ≥ 1 additional ALC measurement recorded afterward. The analysis included all ALC data collected within 780 days from index date. Laboratory results were sourced from Quest Diagnostics and linked with patient data from the Komodo Health database, encompassing both open and closed claims. The Asian subgroup was excluded from the analysis because of insufficient numbers of patients with available ALC measurements.
Compliance with Ethics Guidelines
This study was a retrospective analysis of de-identified data from the Komodo Health database and did not involve any new studies with human or animal subjects. As such, ethical approval or informed consent was not required.
Statistical Methods
Patient demographics and baseline characteristics, including sociodemographic characteristics, were analyzed descriptively. The Quan–Charlson comorbidity index, a validated approach summarizing disease burden and predicting mortality risk and high healthcare costs, was calculated [ 23 – 26 ]. MS disease severity was derived from a previously published algorithm [ 27 – 29 ]. The algorithm used the binary presences of MS symptoms, DMT utilization, durable medical equipment use (canes, walkers, wheelchairs, and hospital beds), MS-related hospitalizations, and MS relapses as MS disease severity predictors to classify disease into low (0–4), moderate (5–10), and high (≥ 11) MS severity score categories. Means (SD) were used to describe continuous variables while frequencies (%) were used for categorical variables. Data are presented for Black, Hispanic, Asian, and white PwMS.
Pre- versus post-index ARRs and encounter rates were estimated from Poisson generalized linear models adjusted for repeated measures correlation and offset for time. Similarly, HCCs were estimated from Gamma generalized linear models.
Across racial group analyses, evaluating post-index outcomes during the on-fumarates period, included an offset term for on-treatment follow-up time and were adjusted for age, sex, baseline relapses, MS severity score, Charlson comorbidity index, high poverty state, and insurance plan type. Comparisons were made with the white racial group as the reference.
Trends in log-transformed ALC were estimated using linear mixed-effects regression for repeated measures with random slopes and intercepts to account for variability across patients’ ALC trajectories. Spatial Gaussian correlation structures were used to account for the uneven spacing of the ALC collection schedule observed. Models were adjusted for age, sex, and Quan–Charlson comorbidity index. The estimated percentage changes in ALC from baseline to month 12 across racial groups are presented. The p value represents the estimated mean trend difference between the specified race group versus white at the noted time point.
Results
Patient Population
Overall, there were 439,928 people with a diagnosis for MS and ≥ 1 DMT claim between 1 January 2016 and 31 May 2022 in the Komodo Health database (Fig. 1 ). After exclusion criteria were applied, 6800 PwMS received fumarates and had known status for race/ethnicity, including 1241 Black, 777 Hispanic, 132 Asian, and 4650 white PwMS. The baseline patient demographics and disease characteristics are shown by race in Table 1 . The post-index duration (days [SD]) of fumarates exposure was 449 (412) in Black, 488 (424) in Hispanic, 559 (459) in Asian, and 554 (470) in white PwMS. A lower proportion of Black PwMS (41.8%) used commercial insurance compared with Asian (68.9%), white (62.1%), and Hispanic (58.7%) PwMS. More Black (33.8%) and Hispanic (31.9%) PwMS lived in states with high poverty levels compared with white (23.5%) and Asian (22.7%) PwMS. Baseline mean (SD) MS severity scores were higher in Black PwMS, 7.08 (4.18), compared with Hispanic, 6.40 (4.03); Asian, 6.03 (3.32); and white, 6.42 (4.08) PwMS. Baseline mean (SD) Quan–Charlson comorbidity index scores were also higher in Black PwMS (0.72 [1.31]) compared with Hispanic (0.65 [1.21]), Asian (0.52 [1.13]), and white (0.56 [1.09]) PwMS. The most common comorbidity was chronic pulmonary disease, occurring predominantly in Black PwMS ( n = 209, 16.8%), compared with Hispanic ( n = 116, 14.9%), Asian ( n = 12, 9.1%), and white ( n = 625, 13.4%) PwMS. In addition, more Black PwMS ( n = 43; 3.5%) had congestive heart failure compared with Hispanic ( n = 11, 1.4%), Asian ( n = 1, 0.8%), and white ( n = 78, 1.7%) PwMS. Finally, diabetes without complications at baseline was more common in Black PwMS than in other racial/ethnic groups ( n = 152, 12.2%; n = 61, 7.9%; n = 9, 6.8%; and n = 340, 7.3% for Black, Hispanic, Asian, and white PwMS, respectively). Fig. 1 Patient selection. DMT disease-modifying therapy, ICD-9-CM International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-10 International Classification of Diseases, Tenth Revision, MS multiple sclerosis, PwMS people with MS. a ICD-9-CM diagnosis code 340 or ICD-10 code G35 Table 1 Patient demographics and baseline characteristics Black ( n = 1241) Hispanic or Latino ( n = 777) Asian ( n = 132) White ( n = 4650) Female, n (%) 1010 (81.4) 561 (72.2) 90 (68.2) 3494 (75.1) Age, years, mean (SD) 43.45 (11.23) 41.42 (11.37) 41.83 (11.18) 46.66 (10.91) Age group, years, n (%) 18–29 151 (12.2) 121 (15.6) 22 (16.7) 346 (7.4) 30–39 324 (26.1) 237 (30.5) 34 (25.8) 887 (19.1) 40–49 352 (28.4) 206 (26.5) 42 (31.8) 1363 (29.3) 50–59 311 (25.1) 169 (21.8) 26 (19.7) 1440 (31.0) 60–64 103 (8.3) 44 (5.7) 8 (6.1) 614 (13.2) Region, n (%) Midwest 277 (22.3) 91 (11.7) 30 (22.7) 1327 (28.5) Northeast 241 (19.4) 188 (24.2) 27 (20.5) 1105 (23.8) South 615 (49.6) 273 (35.1) 26 (19.7) 1398 (30.1) West 83 (6.7) 212 (27.3) 49 (37.1) 759 (16.3) Unknown 25 (2.0) 13 (1.7) 0 61 (1.3) Insurance type, n (%) Commercial 519 (41.8) 456 (58.7) 91 (68.9) 2886 (62.1) Medicaid 496 (40.0) 223 (28.7) 36 (27.3) 957 (20.6) Medicare 226 (18.2) 98 (12.6) 5 (3.8) 807 (17.4) Reside in state with high level of poverty, n (%) a 417 (33.8) 248 (31.9) 30 (22.7) 1094 (23.5) ARR 12 months pre-index b,c 0.338 0.311 0.295 0.299 Number of relapses 12 months pre-index, n (%) b 0 926 (74.6) 597 (76.8) 100 (75.8) 3717 (79.9) 1 260 (21.0) 155 (19.9) 26 (19.7) 741 (15.9) 2+ 55 (4.4) 25 (3.2) 6 (4.6) 192 (4.1) MS severity score, mean (SD) 7.08 (4.18) 6.40 (4.03) 6.03 (3.32) 6.42 (4.08) MS severity, n (%) Low (score of 0–4) 380 (30.9) 286 (37.1) 53 (40.5) 1679 (36.5) Moderate (score of 5–10) 633 (51.5) 389 (50.5) 65 (49.6) 2399 (52.1) High (score of ≥ 11) 217 (17.6) 96 (12.5) 13 (9.9) 526 (11.4) Quan–Charlson comorbidity index, mean (SD) 0.72 (1.3) 0.65 (1.2) 0.52 (1.1) 0.56 (1.1) Quan–Charlson comorbidity d , n (%) Chronic pulmonary disease 209 (16.8) 116 (14.9) 12 (9.1) 625 (13.4) Cerebrovascular disease 132 (10.6) 60 (7.7) 8 (6.1) 348 (7.5) Diabetes without complications 152 (12.2) 61 (7.9) 9 (6.8) 340 (7.3) Paraplegia and hemiplegia 106 (8.5) 57 (7.3) 7 (5.3) 267 (5.7) Mild liver disease 36 (2.9) 42 (5.4) 9 (6.8) 209 (4.5) Peripheral vascular disease 31 (2.5) 22 (2.8) 4 (3.0) 162 (3.5) Diabetes with complications 64 (5.2) 39 (5.0) 3 (2.3) 151 (3.2) Cancer 39 (3.1) 19 (2.4) 4 (3.0) 145 (3.1) Renal disease 33 (2.7) 17 (2.2) 4 (3.0) 95 (2.0) Connective tissue/rheumatic disease 36 (2.9) 28 (3.6) 1 (0.8) 92 (2.0) Congestive heart failure 43 (3.5) 11 (1.4) 1 (0.8) 78 (1.7) Myocardial infarction 15 (1.2) 5 (0.6) 0 (0.0) 61 (1.3) Dementia 18 (1.5) 8 (1.0) 0 (0.0) 46 (1.0) Peptic ulcer disease 10 (0.8) 1 (0.1) 1 (0.8) 28 (0.6) Metastatic carcinoma 7 (0.6) 4 (0.5) 1 (0.8) 20 (0.4) Moderate or severe liver disease 2 (0.2) 0 (0.0) 0 (0.0) 7 (0.2) AIDS/HIV 4 (0.3) 2 (0.3) 0 (0.0) 4 (0.1) ARR annualized relapse rate, MS multiple sclerosis, SD standard deviation a State ranks in the top quartile for the proportion of residents who live in poverty based on 2021 US Census Bureau of Statistics (LA, MS, NM, DC, WV, AL, KY, OK, SC, GA, TX, NV, NY) b ARR calculated as the total number of relapses observed divided by the total number of patient-years observed. Estimated via Poisson model adjusting for repeated measures correlation c Relapses were defined as an MS-related inpatient claim with a primary diagnosis of MS or an outpatient MS-related diagnosis and prescription claim for an intravenous steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid ≤ 7 days after the outpatient visit d Quan–Charlson comorbidities present in at least 10% of any racial/ethnic subgroup
Patient selection. DMT disease-modifying therapy, ICD-9-CM International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-10 International Classification of Diseases, Tenth Revision, MS multiple sclerosis, PwMS people with MS. a ICD-9-CM diagnosis code 340 or ICD-10 code G35
Table 1 Patient demographics and baseline characteristics Black ( n = 1241) Hispanic or Latino ( n = 777) Asian ( n = 132) White ( n = 4650) Female, n (%) 1010 (81.4) 561 (72.2) 90 (68.2) 3494 (75.1) Age, years, mean (SD) 43.45 (11.23) 41.42 (11.37) 41.83 (11.18) 46.66 (10.91) Age group, years, n (%) 18–29 151 (12.2) 121 (15.6) 22 (16.7) 346 (7.4) 30–39 324 (26.1) 237 (30.5) 34 (25.8) 887 (19.1) 40–49 352 (28.4) 206 (26.5) 42 (31.8) 1363 (29.3) 50–59 311 (25.1) 169 (21.8) 26 (19.7) 1440 (31.0) 60–64 103 (8.3) 44 (5.7) 8 (6.1) 614 (13.2) Region, n (%) Midwest 277 (22.3) 91 (11.7) 30 (22.7) 1327 (28.5) Northeast 241 (19.4) 188 (24.2) 27 (20.5) 1105 (23.8) South 615 (49.6) 273 (35.1) 26 (19.7) 1398 (30.1) West 83 (6.7) 212 (27.3) 49 (37.1) 759 (16.3) Unknown 25 (2.0) 13 (1.7) 0 61 (1.3) Insurance type, n (%) Commercial 519 (41.8) 456 (58.7) 91 (68.9) 2886 (62.1) Medicaid 496 (40.0) 223 (28.7) 36 (27.3) 957 (20.6) Medicare 226 (18.2) 98 (12.6) 5 (3.8) 807 (17.4) Reside in state with high level of poverty, n (%) a 417 (33.8) 248 (31.9) 30 (22.7) 1094 (23.5) ARR 12 months pre-index b,c 0.338 0.311 0.295 0.299 Number of relapses 12 months pre-index, n (%) b 0 926 (74.6) 597 (76.8) 100 (75.8) 3717 (79.9) 1 260 (21.0) 155 (19.9) 26 (19.7) 741 (15.9) 2+ 55 (4.4) 25 (3.2) 6 (4.6) 192 (4.1) MS severity score, mean (SD) 7.08 (4.18) 6.40 (4.03) 6.03 (3.32) 6.42 (4.08) MS severity, n (%) Low (score of 0–4) 380 (30.9) 286 (37.1) 53 (40.5) 1679 (36.5) Moderate (score of 5–10) 633 (51.5) 389 (50.5) 65 (49.6) 2399 (52.1) High (score of ≥ 11) 217 (17.6) 96 (12.5) 13 (9.9) 526 (11.4) Quan–Charlson comorbidity index, mean (SD) 0.72 (1.3) 0.65 (1.2) 0.52 (1.1) 0.56 (1.1) Quan–Charlson comorbidity d , n (%) Chronic pulmonary disease 209 (16.8) 116 (14.9) 12 (9.1) 625 (13.4) Cerebrovascular disease 132 (10.6) 60 (7.7) 8 (6.1) 348 (7.5) Diabetes without complications 152 (12.2) 61 (7.9) 9 (6.8) 340 (7.3) Paraplegia and hemiplegia 106 (8.5) 57 (7.3) 7 (5.3) 267 (5.7) Mild liver disease 36 (2.9) 42 (5.4) 9 (6.8) 209 (4.5) Peripheral vascular disease 31 (2.5) 22 (2.8) 4 (3.0) 162 (3.5) Diabetes with complications 64 (5.2) 39 (5.0) 3 (2.3) 151 (3.2) Cancer 39 (3.1) 19 (2.4) 4 (3.0) 145 (3.1) Renal disease 33 (2.7) 17 (2.2) 4 (3.0) 95 (2.0) Connective tissue/rheumatic disease 36 (2.9) 28 (3.6) 1 (0.8) 92 (2.0) Congestive heart failure 43 (3.5) 11 (1.4) 1 (0.8) 78 (1.7) Myocardial infarction 15 (1.2) 5 (0.6) 0 (0.0) 61 (1.3) Dementia 18 (1.5) 8 (1.0) 0 (0.0) 46 (1.0) Peptic ulcer disease 10 (0.8) 1 (0.1) 1 (0.8) 28 (0.6) Metastatic carcinoma 7 (0.6) 4 (0.5) 1 (0.8) 20 (0.4) Moderate or severe liver disease 2 (0.2) 0 (0.0) 0 (0.0) 7 (0.2) AIDS/HIV 4 (0.3) 2 (0.3) 0 (0.0) 4 (0.1) ARR annualized relapse rate, MS multiple sclerosis, SD standard deviation a State ranks in the top quartile for the proportion of residents who live in poverty based on 2021 US Census Bureau of Statistics (LA, MS, NM, DC, WV, AL, KY, OK, SC, GA, TX, NV, NY) b ARR calculated as the total number of relapses observed divided by the total number of patient-years observed. Estimated via Poisson model adjusting for repeated measures correlation c Relapses were defined as an MS-related inpatient claim with a primary diagnosis of MS or an outpatient MS-related diagnosis and prescription claim for an intravenous steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid ≤ 7 days after the outpatient visit d Quan–Charlson comorbidities present in at least 10% of any racial/ethnic subgroup
Patient demographics and baseline characteristics
ARR annualized relapse rate, MS multiple sclerosis, SD standard deviation
a State ranks in the top quartile for the proportion of residents who live in poverty based on 2021 US Census Bureau of Statistics (LA, MS, NM, DC, WV, AL, KY, OK, SC, GA, TX, NV, NY)
b ARR calculated as the total number of relapses observed divided by the total number of patient-years observed. Estimated via Poisson model adjusting for repeated measures correlation
c Relapses were defined as an MS-related inpatient claim with a primary diagnosis of MS or an outpatient MS-related diagnosis and prescription claim for an intravenous steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid ≤ 7 days after the outpatient visit
d Quan–Charlson comorbidities present in at least 10% of any racial/ethnic subgroup
Study Outcomes
ARRs were significantly reduced across all racial/ethnic groups when comparing 12-month pre-index to post-index relapse rates. The mean (95% CI) ARR was reduced from 0.338 (95% CI 0.297–0.385) to 0.252 (95% CI 0.212–0.300) for Black PwMS, 0.311 (95% CI 0.258–0.376) to 0.185 (95% CI 0.138–0.248) for Hispanic PwMS, 0.295 (95% CI 0.212–0.412) to 0.163 (95% CI 0.104–0.256) for Asian PwMS, and 0.299 (95% CI 0.273–0.326) to 0.214 (95% CI 0.182–0.251) for white PwMS (Fig. 2 a). Fig. 2 a ARR 12 months pre-index and post-index and b post-index adjusted ARR ratio vs. white PwMS. ARR calculated as the total number of relapses observed divided by the total number of patient-years observed. Estimated via Poisson model adjusting for repeated measures correlation. Error bars represent the 95% CI. ARR annualized relapse rate, CI confidence interval, MS multiple sclerosis, PwMS people with MS. a Based on Poisson model adjusting for baseline relapse rate, age, sex, and MS severity score. Rate ratio > 1 favors the white racial group
a ARR 12 months pre-index and post-index and b post-index adjusted ARR ratio vs. white PwMS. ARR calculated as the total number of relapses observed divided by the total number of patient-years observed. Estimated via Poisson model adjusting for repeated measures correlation. Error bars represent the 95% CI. ARR annualized relapse rate, CI confidence interval, MS multiple sclerosis, PwMS people with MS. a Based on Poisson model adjusting for baseline relapse rate, age, sex, and MS severity score. Rate ratio > 1 favors the white racial group
After adjusting for racial disparities in MS disease activity and comorbidity burden, the post-index rate ratios for fumarates did not show a significant difference between racial/ethnic subgroups and the white subgroup (Fig. 2 b). The adjusted ARR ratio for Black PwMS was 1.195 (95% CI 0.999–1.428). For Hispanic PwMS, it was 0.839 (95% CI 0.667–1.053), and for Asian PwMS, it was 1.053 (95% CI 0.642–1.710). However, none of these differences reached statistical significance ( p > 0.05 for all).
The adjusted Kaplan–Meier estimated proportion of PwMS who remained relapse-free at 24 months was comparable across all racial/ethnic groups (Fig. 3 ). The estimated proportions of patients remaining relapse-free at 24-months (95% CI) were 77.0% (73.7–80.3%) for Black PwMS, 75.4% (71.0–80.0%) for Hispanic PwMS, 81.7% (73.0–90.3%) for Asian PwMS, and 80.5% (70.0–82.1%) for white PwMS. There were no statistically significant differences in the Black, Hispanic, and Asian groups compared with the white group ( p > 0.05). Fig. 3 Time to first post-index relapse in Black, Hispanic, Asian, and white PwMS. CI confidence interval, MS multiple sclerosis, PwMS people with MS. a Relapses were defined as an MS-related inpatient claim with a primary diagnosis of MS or an outpatient MS-related diagnosis and prescription claim for an intravenous steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid ≤ 7 days after the outpatient visit. b Cox proportional hazards model was adjusted for age, sex, baseline relapses, and MS severity score. p values are based on a modified version of the Pepe and Fleming test comparing the difference in adjusted Kaplan–Meier survival curve versus white (reference group)
Time to first post-index relapse in Black, Hispanic, Asian, and white PwMS. CI confidence interval, MS multiple sclerosis, PwMS people with MS. a Relapses were defined as an MS-related inpatient claim with a primary diagnosis of MS or an outpatient MS-related diagnosis and prescription claim for an intravenous steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid ≤ 7 days after the outpatient visit. b Cox proportional hazards model was adjusted for age, sex, baseline relapses, and MS severity score. p values are based on a modified version of the Pepe and Fleming test comparing the difference in adjusted Kaplan–Meier survival curve versus white (reference group)
From month 0 to month 12, the decline in ALC was less in Black PwMS compared with other racial/ethnic groups (Fig. 4 ). The estimated ALC reduction was 10.3% (95% CI 3.8–16.3%) for Black PwMS, compared with 20.1% (95% CI 14.8–25.1%) for Hispanic PwMS, and 20.4% (95% CI 18.0–22.7%) for white PwMS. The difference in ALC reduction between Black and white PwMS was statistically significant ( p = 0.010), whereas the comparison between Hispanic and white PwMS showed no significant difference ( p = 0.999). There were not enough ALC data available to analyze in the Asian subgroup. Fig. 4 Estimated ALC at baseline and 12 months post-index. Patients included must have had an ALC measure at month 0 and ≥ 1 subsequent ALC measurement. Too few ALC data from Asian people with MS were obtained for the analysis to be meaningful. p values represent the estimated mean trend difference between the specified race group vs. white at the noted time point. Error bars represent the 95% CI. ALC absolute lymphocyte count, CI confidence interval, MS multiple sclerosis
Estimated ALC at baseline and 12 months post-index. Patients included must have had an ALC measure at month 0 and ≥ 1 subsequent ALC measurement. Too few ALC data from Asian people with MS were obtained for the analysis to be meaningful. p values represent the estimated mean trend difference between the specified race group vs. white at the noted time point. Error bars represent the 95% CI. ALC absolute lymphocyte count, CI confidence interval, MS multiple sclerosis
Post-index, the mean MS-related adjusted annualized per-patient per-year HRU rates (95% CI) were 3.57 (3.47–3.67; p = 0.404 vs. white) for Black PwMS; 3.60 (3.48–3.73; p = 0.251 vs. white) for Hispanic PwMS; 3.67 (3.40–3.97; p = 0.554 vs. white) for Asian PwMS; and 3.48 (3.42–3.54; reference group) for white PwMS (Supplementary Material Fig. S1 A). With regard to the HRU rate of 3.57 for Black PwMS, this number indicates that, on average, Black patients interacted with the healthcare system for MS-related reasons 3.57 times per year. Additionally, the HRU rates for all racial/ethnic subgroups were not significantly different from the white patient population.
The mean MS-related adjusted annualized per-patient per-year HCCs (95% CI) post-index were $4559 (3955–5256), $4293 (3625–5084), $3525 (2429–5116), and $4261 (3911–4643) for Black, Hispanic, Asian, and white PwMS, respectively (Supplementary Material Fig. S1 B).
Discussion
The Komodo claims-based database allows for the observation of real-world DMT utilization and assessment of its effectiveness in MS across different racial and ethnic groups. By capturing self-reported race and ethnicity data, we were able to conduct comparative analyses, shedding light on important disparities in healthcare access and outcomes. In this study, Black PwMS were less likely to use commercial insurance plans and were more likely to rely on Medicare/Medicaid compared with Hispanic, Asian, or white PwMS. Additionally, Black PwMS presented with more severe MS at baseline compared with these other groups and were more likely to reside in a state with a higher rate of poverty than white PwMS. Black PwMS had a higher mean MS severity score (7.08 vs. 6.42 in white PwMS) and a greater comorbidity burden (mean Quan–Charlson index of 0.72 vs. 0.56), with higher rates of conditions such as chronic pulmonary disease, diabetes, and congestive heart failure. These observed differences suggest that outcomes are not solely due to biological factors but are also influenced by SDOH—specifically, limited insurance coverage, higher poverty levels, and reduced health literacy—which play a significant role in the elevated baseline disease burden observed in Black PwMS [ 19 ]. Previous studies have shown that minority racial/ethnic groups in the USA may encounter barriers in accessing and utilizing specialty care due to limited or lack of insurance, lower income, lower education levels, and language and computer literacy barriers [ 6 ].
These baseline disparities reflect broader systemic challenges in healthcare that further worsen outcomes in minority patients with MS. In the USA, systemic differences in healthcare access, socioeconomic inequalities, cognitive biases, and racism within the healthcare system may contribute to poorer disease-related outcomes in people from minority racial and ethnic groups [ 20 ]. According to Amezcua et al., Black and Hispanic PwMS often have lower health literacy and face reduced access to specialty care and delays in diagnosis due to systemic and structural racism in healthcare. These factors exacerbate disparities in disease outcomes and access to effective treatments [ 20 ]. Addressing these issues requires systemic interventions, including integrating SDOH data into health records and training providers to reduce biases [ 20 ].
In this study, Black PwMS had a higher baseline Quan–Charlson comorbidity index than other racial/ethnic groups and had fewer days of fumarates exposure post-index than Hispanic, Asian, and white PwMS. This could suggest potential disparities in access to treatments, but it is also possible that other factors contributed to the lower exposure, such as differences in patient preferences, or healthcare provider perceptions. The US Centers for Disease Control and Prevention has emphasized that addressing these barriers first begins with recognizing and bringing awareness to them [ 30 ].
Previous studies have suggested that outcomes in Black PwMS are poorer than those of their non-Black counterparts, although MS has not been adequately studied in minority racial/ethnic groups because of low recruitment of these patients in clinical trials [ 4 – 6 ]. This study included 2150 PwMS from minority racial/ethnic groups and compared outcomes with 4650 white PwMS. The estimated proportion of patients who were relapse-free at 24 months post-index was comparable across all racial/ethnic groups. Despite Black PwMS having a higher pre-index ARR than Hispanic, Asian, and white PwMS, significant reductions in ARR from 12 months pre-index to 12 months post-index were observed across all racial/ethnic groups following fumarate treatment. This indicates that fumarates are effective across racial and ethnic subgroups. These results are consistent with previous studies, including a post hoc analysis of the phase 3 DEFINE and CONFIRM studies, which showed that DMF treatment in Black, Hispanic, and Asian patients with MS was associated with a lower ARR at 2 years and lower 12-week confirmed disability progression compared with placebo treatment [ 14 ]. Furthermore, a retrospective chart review ( N = 390) in patients with relapsing/refractory MS showed that the effectiveness and tolerability of DMF were similar across African American ( n = 69), Hispanic American ( n = 52), and white American patient groups ( n = 261) [ 15 ]. A recent analysis of the phase 4 ESTEEM study found that DMF reduced ARR in Black and Hispanic PwMS, with 5-year outcomes consistent in non-Black and non-Hispanic PwMS [ 17 ]. Additionally, a recent subgroup analysis of Black PwMS from the EVOLVE-MS-1 study supported DRF as an effective treatment option in the Black patient subgroup [ 18 ].
In this study, we compared MS-related HRU and HCC rates in Black, Hispanic, Asian, and white PwMS. All four patient cohorts studied experienced similar annualized rates of healthcare encounters, as well as similar annualized HCCs. These findings indicate that treatment of Black, Hispanic, and Asian PwMS with fumarates provides HRU and HCC rates that were comparable with white PwMS.
The safety profile of DMF treatment in Black and Hispanic PwMS was consistent with the overall population, although there is evidence suggesting a less pronounced reduction in mean lymphocyte counts in Black patients [ 17 ]. In our study, Black PwMS exhibited a smaller decline in ALC at 12 months post-index compared with Hispanic, Asian, and white PwMS. This finding aligns with data from the EVOLVE-MS-1 study, in which Black patients treated with DRF had lower rates of lymphopenia and less pronounced lymphocyte declines than non-Black patients, without the emergence of new safety signals [ 18 ]. However, it is important to note that the observed decline in ALC does not appear to be directly driving the efficacy of the treatment. The relationship between lymphocyte counts and treatment effectiveness is not necessarily causal, and caution should be used when interpreting these ALC results, as they may be independent of efficacy outcomes. Furthermore, as a result of the low number of patients with available laboratory data (Black, n = 53; Hispanic, n = 73; white, n = 329), future research with larger, more racially and ethnically inclusive cohorts is needed to confirm these findings.
This study has several limitations, which are typical of real-world, observational, claims-based studies. These include the lack of randomization, potential coding errors, the inability to confirm reported diagnoses, and challenges in accurately assessing MS disease severity. Relapses were captured only if they led to an outpatient visit, hospital admission, or ER visit, meaning milder relapses not prompting healthcare interactions could be underestimated. Additionally, treatments not billed within 7 days were not captured. The analysis also did not stratify outcomes by patient age, so potential age-related differences in disease course or treatment response could not be evaluated. In the Komodo Health claims database, race and ethnicity were self-reported either as a single designation (e.g., Black or Hispanic, but not both) or as separate fields (e.g., Black race and Hispanic ethnicity). To ensure consistency, Komodo Health consolidates race and ethnicity data into one combined field using the data source of the highest available quality when > 1 is available. Patients reporting their race as “other” were not included. The study also lacked imaging or genomic data and had a limited ALC/laboratory data. Additionally, Expanded Disability Status Scale data were not available to assess higher disability in the Black PwMS group, who were more likely to use Medicare/Medicaid insurance than other racial/ethnic groups. Although the Komodo Health database is one of the largest in the USA, the findings may not be generalizable to other countries. Despite these limitations, analysis of claims data is a valuable tool that has been applied previously to assess DMT treatment patterns, relapses, HRU, and HCCs in the real-world clinical care of patients with MS [ 31 – 33 ].
Conclusions
This large, real-world, claims-based analysis confirmed the benefit of fumarates treatment in 2150 PwMS who self-reported being in a racial/ethnic minority group (Black, Hispanic, or Asian). This is the largest analysis to date of the treatment effects of any individual class of DMT in Black and Hispanic PwMS. Consistent with previous studies, the effectiveness of fumarates was similar across all racial/ethnic groups in this analysis.
Supplementary Information
Below is the link to the electronic supplementary material. Supplementary file1 (PDF 189 KB)
Supplementary file1 (PDF 189 KB)
Why carry out this study? Racial and ethnic minority people with multiple sclerosis (PwMS) have been reported to have a worse clinical course and disability outcomes than white PwMS, although multiple sclerosis (MS) is not adequately studied in these groups. To compare the real-world effectiveness of fumarates across Black, Hispanic, Asian, and white PwMS in the USA. What was learned from this study? Further confirmation that Black and Hispanic PwMS have higher disease burden at baseline. Fumarates were effective across all racial/ethnic groups in this real-world study. Black PwMS exhibited a smaller decline in absolute lymphocyte counts at 12 months post initiation of fumarates compared with Hispanic, Asian, and white PwMS.
Why carry out this study? Racial and ethnic minority people with multiple sclerosis (PwMS) have been reported to have a worse clinical course and disability outcomes than white PwMS, although multiple sclerosis (MS) is not adequately studied in these groups. To compare the real-world effectiveness of fumarates across Black, Hispanic, Asian, and white PwMS in the USA. What was learned from this study? Further confirmation that Black and Hispanic PwMS have higher disease burden at baseline. Fumarates were effective across all racial/ethnic groups in this real-world study. Black PwMS exhibited a smaller decline in absolute lymphocyte counts at 12 months post initiation of fumarates compared with Hispanic, Asian, and white PwMS.
Digital Features
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Introduction
Multiple sclerosis (MS) is a complex and heterogeneous disease that affects a diverse population worldwide, with approximately 2.9 million people living with the disease globally, and nearly 1 million residing in the USA [ 1 ]. Of the total US population, 20% are Hispanic/Latino, 14% are Black/African American, and 6% are Asian [ 2 ]. It is crucial to study these patients from minority groups, as MS prevalence and progression can differ significantly across them. For example, Black individuals are reported to have a higher incidence of MS than white individuals, while Asian and Hispanic populations have lower incidences [ 3 ]. Moreover, Black people with MS (PwMS) tend to experience a more severe disease course, with more frequent relapses and faster disability progression compared with non-Black individuals [ 4 – 6 ]. Despite these disparities, there is limited research on MS in minority populations, primarily due to their underrepresentation in clinical trials [ 7 , 8 ]. In addition, only 14 out of 45 (31.1%) phase 3 trials in PwMS reported participants’ racial breakdowns, highlighting a significant data gap in these populations from a research perspective.
Dimethyl fumarate (DMF) and diroximel fumarate (DRF) are oral fumarate disease-modifying therapies (DMTs) with favorable efficacy and safety profiles that are approved for treating relapsing forms of MS [ 9 – 11 ]. As of 31 December 2023, approximately 607,448 patients have been treated with DMF (approx. 1.4 million person-years of exposure) [ 12 ], while approximately 44,297 patients have been treated with DRF (approx. 61,780 person-years of exposure) [ 13 ]. Previous studies have demonstrated the efficacy and safety of fumarates across patients from racial and ethnic minority groups with MS [ 14 – 17 ]. Recent findings from a post hoc analysis of the phase 3 EVOLVE-MS-1 study showed that DRF was an effective treatment option for Black PwMS, with similar outcomes to non-Black patient subgroups [ 18 ]. However, these studies were limited in number, often involved small patient populations, and did not adequately account for potential differences in MS presentation. In addition, social determinants of health (SDOH), which include socioeconomic status and access to healthcare, as well as the conditions into which people are born, live, work, and age, can affect MS outcomes and were not reported in these previous studies [ 19 ]. Disparities in healthcare access, lower health literacy, and biases in treatment decisions can contribute to worse MS outcomes in minority populations, suggesting that disease burden may not be fully explained by biological differences alone [ 19 , 20 ].
The underrepresentation of racial and ethnic minorities in clinical trials poses a significant challenge to understanding the differential impact of MS therapies across diverse populations. This study aims to address this gap by evaluating the real-world effectiveness of fumarates (both DMF and DRF) among Black, Hispanic, Asian, and white PwMS using the Komodo Health claims database. By including a substantial number of minority patients and considering factors such as state poverty level and type of insurance plan, this study seeks to provide a more comprehensive evaluation of how these therapies perform across different racial and ethnic groups.
We hypothesize that the effectiveness of fumarates will be consistent across these diverse populations. This research is crucial in filling the gaps left by previous studies, contributing valuable data to support more inclusive treatment strategies in MS care.
Methods
Study Design
This retrospective analysis used closed claims in the Komodo Health claims database to determine changes in efficacy outcomes after fumarates treatment in Black, Hispanic, Asian, and white PwMS. The Komodo Health database, a real-world, multipayer claims databases in the USA, integrates disparate sources of patient-level data to map longitudinal patient journeys. Komodo pulls de-identified, patient-level claims data from > 150 payers and provider data sources. Data on race and ethnicity was collected for patients who had an outpatient, inpatient, or emergency room (ER) visit and who chose to report race/ethnicity. Race and ethnicity were self-reported in one of two ways: either as a single designation (e.g., reporting as only Black or only Hispanic) or as separate fields, allowing for “Black” as race and “Hispanic” as ethnicity. In data reports where both race and ethnicity are provided, Komodo Health database used race over ethnicity. Alternately, if a patient provided ethnicity such as Hispanic as the first choice and race and ethnicity such as white, Hispanic as a second choice, the data were rank-ordered to choose ethnicity as the reportable data point. To ensure consistency, the Komodo Health database consolidates race and ethnicity data into one field [ 21 ]. The designations were (1) Black people, which included those who reported their race as Black or African American, (2) Hispanic people, which included those who reported their ethnicity as Hispanic or Latino, and (3) Asian people, which included those who reported their race as Asian or Pacific Islander (defined as persons having origins in any of the original peoples of the Far East, Southeast Asia, the Indian subcontinent, Hawaii, Guam, Samoa, or other Pacific Islands).
Patients
PwMS included in this study were 18–64 years old and had ≥ 1 claim for MS diagnosis (based on International Classification of Disease [ICD]-9 and ICD-10 diagnosis codes) from 01 January 2016 to 31 August 2022, and a claim for DMF (including TECFIDERA ® or generic DMF) or DRF (VUMERITY ® ) between 01 January 2017 and 31 May 2022. The index date was defined as the earliest date of the first fumarates claim (i.e., the first documented paid prescription fill date of fumarates treatment). Eligible patients also had continuous medical and pharmacy enrollment for 1 year prior to the index date (≤ 45-day gap) and ≥ 3 months continuous enrollment and continuous exposure to DMT after index date (≤ 45-day gap). Patients who switched from another oral or injectable DMT such as interferon-beta, glatiramer acetate, teriflunomide, fingolimod, ponesimod, siponimod, or cladribine to fumarates therapy were eligible for inclusion. Patients were excluded if they had multiple DMTs on the fumarates index date or had monoclonal antibody DMT at any time pre-index date.
PwMS were followed from index date to the end of study (31 May 2022), end of insurance eligibility, a gap in index DMT of > 45 days, or a switch from index DMT to another DMT, whichever occurred first.
Outcomes
The primary outcome was the change in annualized relapse rate (ARR) from 12 months pre-index to 12 months post-index. Relapses were defined as an MS-related inpatient claim with a primary diagnosis of MS (ICD 9/10 codes 340/G35) or an outpatient MS-related diagnosis plus a prescription claim for an intravenous (IV) steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid (≥ 500 mg/day prednisone or equivalent) ≤ 7 days after the outpatient visit [ 22 ]. Relapses that occurred within 30 days were considered as a single episode. Mild relapses that did not prompt a patient to interact with the healthcare system were not captured in claims data.
Secondary outcomes were the post-index ARR by racial strata versus white, time to first relapse post-index (up to month 24), absolute lymphocyte counts (ALCs) from baseline to 12 months post-index, and health and post-index MS-related costs. MS-related healthcare resource utilization (HRU) and healthcare costs (HCCs) were identified by claims with an associated MS diagnosis code of G35.
To be included in the ALC subgroup analyses, patients were required to have an ALC measurement at month 0 and ≥ 1 additional ALC measurement recorded afterward. The analysis included all ALC data collected within 780 days from index date. Laboratory results were sourced from Quest Diagnostics and linked with patient data from the Komodo Health database, encompassing both open and closed claims. The Asian subgroup was excluded from the analysis because of insufficient numbers of patients with available ALC measurements.
Compliance with Ethics Guidelines
This study was a retrospective analysis of de-identified data from the Komodo Health database and did not involve any new studies with human or animal subjects. As such, ethical approval or informed consent was not required.
Statistical Methods
Patient demographics and baseline characteristics, including sociodemographic characteristics, were analyzed descriptively. The Quan–Charlson comorbidity index, a validated approach summarizing disease burden and predicting mortality risk and high healthcare costs, was calculated [ 23 – 26 ]. MS disease severity was derived from a previously published algorithm [ 27 – 29 ]. The algorithm used the binary presences of MS symptoms, DMT utilization, durable medical equipment use (canes, walkers, wheelchairs, and hospital beds), MS-related hospitalizations, and MS relapses as MS disease severity predictors to classify disease into low (0–4), moderate (5–10), and high (≥ 11) MS severity score categories. Means (SD) were used to describe continuous variables while frequencies (%) were used for categorical variables. Data are presented for Black, Hispanic, Asian, and white PwMS.
Pre- versus post-index ARRs and encounter rates were estimated from Poisson generalized linear models adjusted for repeated measures correlation and offset for time. Similarly, HCCs were estimated from Gamma generalized linear models.
Across racial group analyses, evaluating post-index outcomes during the on-fumarates period, included an offset term for on-treatment follow-up time and were adjusted for age, sex, baseline relapses, MS severity score, Charlson comorbidity index, high poverty state, and insurance plan type. Comparisons were made with the white racial group as the reference.
Trends in log-transformed ALC were estimated using linear mixed-effects regression for repeated measures with random slopes and intercepts to account for variability across patients’ ALC trajectories. Spatial Gaussian correlation structures were used to account for the uneven spacing of the ALC collection schedule observed. Models were adjusted for age, sex, and Quan–Charlson comorbidity index. The estimated percentage changes in ALC from baseline to month 12 across racial groups are presented. The p value represents the estimated mean trend difference between the specified race group versus white at the noted time point.
Results
Patient Population
Overall, there were 439,928 people with a diagnosis for MS and ≥ 1 DMT claim between 1 January 2016 and 31 May 2022 in the Komodo Health database (Fig. 1 ). After exclusion criteria were applied, 6800 PwMS received fumarates and had known status for race/ethnicity, including 1241 Black, 777 Hispanic, 132 Asian, and 4650 white PwMS. The baseline patient demographics and disease characteristics are shown by race in Table 1 . The post-index duration (days [SD]) of fumarates exposure was 449 (412) in Black, 488 (424) in Hispanic, 559 (459) in Asian, and 554 (470) in white PwMS. A lower proportion of Black PwMS (41.8%) used commercial insurance compared with Asian (68.9%), white (62.1%), and Hispanic (58.7%) PwMS. More Black (33.8%) and Hispanic (31.9%) PwMS lived in states with high poverty levels compared with white (23.5%) and Asian (22.7%) PwMS. Baseline mean (SD) MS severity scores were higher in Black PwMS, 7.08 (4.18), compared with Hispanic, 6.40 (4.03); Asian, 6.03 (3.32); and white, 6.42 (4.08) PwMS. Baseline mean (SD) Quan–Charlson comorbidity index scores were also higher in Black PwMS (0.72 [1.31]) compared with Hispanic (0.65 [1.21]), Asian (0.52 [1.13]), and white (0.56 [1.09]) PwMS. The most common comorbidity was chronic pulmonary disease, occurring predominantly in Black PwMS ( n = 209, 16.8%), compared with Hispanic ( n = 116, 14.9%), Asian ( n = 12, 9.1%), and white ( n = 625, 13.4%) PwMS. In addition, more Black PwMS ( n = 43; 3.5%) had congestive heart failure compared with Hispanic ( n = 11, 1.4%), Asian ( n = 1, 0.8%), and white ( n = 78, 1.7%) PwMS. Finally, diabetes without complications at baseline was more common in Black PwMS than in other racial/ethnic groups ( n = 152, 12.2%; n = 61, 7.9%; n = 9, 6.8%; and n = 340, 7.3% for Black, Hispanic, Asian, and white PwMS, respectively). Fig. 1 Patient selection. DMT disease-modifying therapy, ICD-9-CM International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-10 International Classification of Diseases, Tenth Revision, MS multiple sclerosis, PwMS people with MS. a ICD-9-CM diagnosis code 340 or ICD-10 code G35 Table 1 Patient demographics and baseline characteristics Black ( n = 1241) Hispanic or Latino ( n = 777) Asian ( n = 132) White ( n = 4650) Female, n (%) 1010 (81.4) 561 (72.2) 90 (68.2) 3494 (75.1) Age, years, mean (SD) 43.45 (11.23) 41.42 (11.37) 41.83 (11.18) 46.66 (10.91) Age group, years, n (%) 18–29 151 (12.2) 121 (15.6) 22 (16.7) 346 (7.4) 30–39 324 (26.1) 237 (30.5) 34 (25.8) 887 (19.1) 40–49 352 (28.4) 206 (26.5) 42 (31.8) 1363 (29.3) 50–59 311 (25.1) 169 (21.8) 26 (19.7) 1440 (31.0) 60–64 103 (8.3) 44 (5.7) 8 (6.1) 614 (13.2) Region, n (%) Midwest 277 (22.3) 91 (11.7) 30 (22.7) 1327 (28.5) Northeast 241 (19.4) 188 (24.2) 27 (20.5) 1105 (23.8) South 615 (49.6) 273 (35.1) 26 (19.7) 1398 (30.1) West 83 (6.7) 212 (27.3) 49 (37.1) 759 (16.3) Unknown 25 (2.0) 13 (1.7) 0 61 (1.3) Insurance type, n (%) Commercial 519 (41.8) 456 (58.7) 91 (68.9) 2886 (62.1) Medicaid 496 (40.0) 223 (28.7) 36 (27.3) 957 (20.6) Medicare 226 (18.2) 98 (12.6) 5 (3.8) 807 (17.4) Reside in state with high level of poverty, n (%) a 417 (33.8) 248 (31.9) 30 (22.7) 1094 (23.5) ARR 12 months pre-index b,c 0.338 0.311 0.295 0.299 Number of relapses 12 months pre-index, n (%) b 0 926 (74.6) 597 (76.8) 100 (75.8) 3717 (79.9) 1 260 (21.0) 155 (19.9) 26 (19.7) 741 (15.9) 2+ 55 (4.4) 25 (3.2) 6 (4.6) 192 (4.1) MS severity score, mean (SD) 7.08 (4.18) 6.40 (4.03) 6.03 (3.32) 6.42 (4.08) MS severity, n (%) Low (score of 0–4) 380 (30.9) 286 (37.1) 53 (40.5) 1679 (36.5) Moderate (score of 5–10) 633 (51.5) 389 (50.5) 65 (49.6) 2399 (52.1) High (score of ≥ 11) 217 (17.6) 96 (12.5) 13 (9.9) 526 (11.4) Quan–Charlson comorbidity index, mean (SD) 0.72 (1.3) 0.65 (1.2) 0.52 (1.1) 0.56 (1.1) Quan–Charlson comorbidity d , n (%) Chronic pulmonary disease 209 (16.8) 116 (14.9) 12 (9.1) 625 (13.4) Cerebrovascular disease 132 (10.6) 60 (7.7) 8 (6.1) 348 (7.5) Diabetes without complications 152 (12.2) 61 (7.9) 9 (6.8) 340 (7.3) Paraplegia and hemiplegia 106 (8.5) 57 (7.3) 7 (5.3) 267 (5.7) Mild liver disease 36 (2.9) 42 (5.4) 9 (6.8) 209 (4.5) Peripheral vascular disease 31 (2.5) 22 (2.8) 4 (3.0) 162 (3.5) Diabetes with complications 64 (5.2) 39 (5.0) 3 (2.3) 151 (3.2) Cancer 39 (3.1) 19 (2.4) 4 (3.0) 145 (3.1) Renal disease 33 (2.7) 17 (2.2) 4 (3.0) 95 (2.0) Connective tissue/rheumatic disease 36 (2.9) 28 (3.6) 1 (0.8) 92 (2.0) Congestive heart failure 43 (3.5) 11 (1.4) 1 (0.8) 78 (1.7) Myocardial infarction 15 (1.2) 5 (0.6) 0 (0.0) 61 (1.3) Dementia 18 (1.5) 8 (1.0) 0 (0.0) 46 (1.0) Peptic ulcer disease 10 (0.8) 1 (0.1) 1 (0.8) 28 (0.6) Metastatic carcinoma 7 (0.6) 4 (0.5) 1 (0.8) 20 (0.4) Moderate or severe liver disease 2 (0.2) 0 (0.0) 0 (0.0) 7 (0.2) AIDS/HIV 4 (0.3) 2 (0.3) 0 (0.0) 4 (0.1) ARR annualized relapse rate, MS multiple sclerosis, SD standard deviation a State ranks in the top quartile for the proportion of residents who live in poverty based on 2021 US Census Bureau of Statistics (LA, MS, NM, DC, WV, AL, KY, OK, SC, GA, TX, NV, NY) b ARR calculated as the total number of relapses observed divided by the total number of patient-years observed. Estimated via Poisson model adjusting for repeated measures correlation c Relapses were defined as an MS-related inpatient claim with a primary diagnosis of MS or an outpatient MS-related diagnosis and prescription claim for an intravenous steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid ≤ 7 days after the outpatient visit d Quan–Charlson comorbidities present in at least 10% of any racial/ethnic subgroup
Patient selection. DMT disease-modifying therapy, ICD-9-CM International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-10 International Classification of Diseases, Tenth Revision, MS multiple sclerosis, PwMS people with MS. a ICD-9-CM diagnosis code 340 or ICD-10 code G35
Table 1 Patient demographics and baseline characteristics Black ( n = 1241) Hispanic or Latino ( n = 777) Asian ( n = 132) White ( n = 4650) Female, n (%) 1010 (81.4) 561 (72.2) 90 (68.2) 3494 (75.1) Age, years, mean (SD) 43.45 (11.23) 41.42 (11.37) 41.83 (11.18) 46.66 (10.91) Age group, years, n (%) 18–29 151 (12.2) 121 (15.6) 22 (16.7) 346 (7.4) 30–39 324 (26.1) 237 (30.5) 34 (25.8) 887 (19.1) 40–49 352 (28.4) 206 (26.5) 42 (31.8) 1363 (29.3) 50–59 311 (25.1) 169 (21.8) 26 (19.7) 1440 (31.0) 60–64 103 (8.3) 44 (5.7) 8 (6.1) 614 (13.2) Region, n (%) Midwest 277 (22.3) 91 (11.7) 30 (22.7) 1327 (28.5) Northeast 241 (19.4) 188 (24.2) 27 (20.5) 1105 (23.8) South 615 (49.6) 273 (35.1) 26 (19.7) 1398 (30.1) West 83 (6.7) 212 (27.3) 49 (37.1) 759 (16.3) Unknown 25 (2.0) 13 (1.7) 0 61 (1.3) Insurance type, n (%) Commercial 519 (41.8) 456 (58.7) 91 (68.9) 2886 (62.1) Medicaid 496 (40.0) 223 (28.7) 36 (27.3) 957 (20.6) Medicare 226 (18.2) 98 (12.6) 5 (3.8) 807 (17.4) Reside in state with high level of poverty, n (%) a 417 (33.8) 248 (31.9) 30 (22.7) 1094 (23.5) ARR 12 months pre-index b,c 0.338 0.311 0.295 0.299 Number of relapses 12 months pre-index, n (%) b 0 926 (74.6) 597 (76.8) 100 (75.8) 3717 (79.9) 1 260 (21.0) 155 (19.9) 26 (19.7) 741 (15.9) 2+ 55 (4.4) 25 (3.2) 6 (4.6) 192 (4.1) MS severity score, mean (SD) 7.08 (4.18) 6.40 (4.03) 6.03 (3.32) 6.42 (4.08) MS severity, n (%) Low (score of 0–4) 380 (30.9) 286 (37.1) 53 (40.5) 1679 (36.5) Moderate (score of 5–10) 633 (51.5) 389 (50.5) 65 (49.6) 2399 (52.1) High (score of ≥ 11) 217 (17.6) 96 (12.5) 13 (9.9) 526 (11.4) Quan–Charlson comorbidity index, mean (SD) 0.72 (1.3) 0.65 (1.2) 0.52 (1.1) 0.56 (1.1) Quan–Charlson comorbidity d , n (%) Chronic pulmonary disease 209 (16.8) 116 (14.9) 12 (9.1) 625 (13.4) Cerebrovascular disease 132 (10.6) 60 (7.7) 8 (6.1) 348 (7.5) Diabetes without complications 152 (12.2) 61 (7.9) 9 (6.8) 340 (7.3) Paraplegia and hemiplegia 106 (8.5) 57 (7.3) 7 (5.3) 267 (5.7) Mild liver disease 36 (2.9) 42 (5.4) 9 (6.8) 209 (4.5) Peripheral vascular disease 31 (2.5) 22 (2.8) 4 (3.0) 162 (3.5) Diabetes with complications 64 (5.2) 39 (5.0) 3 (2.3) 151 (3.2) Cancer 39 (3.1) 19 (2.4) 4 (3.0) 145 (3.1) Renal disease 33 (2.7) 17 (2.2) 4 (3.0) 95 (2.0) Connective tissue/rheumatic disease 36 (2.9) 28 (3.6) 1 (0.8) 92 (2.0) Congestive heart failure 43 (3.5) 11 (1.4) 1 (0.8) 78 (1.7) Myocardial infarction 15 (1.2) 5 (0.6) 0 (0.0) 61 (1.3) Dementia 18 (1.5) 8 (1.0) 0 (0.0) 46 (1.0) Peptic ulcer disease 10 (0.8) 1 (0.1) 1 (0.8) 28 (0.6) Metastatic carcinoma 7 (0.6) 4 (0.5) 1 (0.8) 20 (0.4) Moderate or severe liver disease 2 (0.2) 0 (0.0) 0 (0.0) 7 (0.2) AIDS/HIV 4 (0.3) 2 (0.3) 0 (0.0) 4 (0.1) ARR annualized relapse rate, MS multiple sclerosis, SD standard deviation a State ranks in the top quartile for the proportion of residents who live in poverty based on 2021 US Census Bureau of Statistics (LA, MS, NM, DC, WV, AL, KY, OK, SC, GA, TX, NV, NY) b ARR calculated as the total number of relapses observed divided by the total number of patient-years observed. Estimated via Poisson model adjusting for repeated measures correlation c Relapses were defined as an MS-related inpatient claim with a primary diagnosis of MS or an outpatient MS-related diagnosis and prescription claim for an intravenous steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid ≤ 7 days after the outpatient visit d Quan–Charlson comorbidities present in at least 10% of any racial/ethnic subgroup
Patient demographics and baseline characteristics
ARR annualized relapse rate, MS multiple sclerosis, SD standard deviation
a State ranks in the top quartile for the proportion of residents who live in poverty based on 2021 US Census Bureau of Statistics (LA, MS, NM, DC, WV, AL, KY, OK, SC, GA, TX, NV, NY)
b ARR calculated as the total number of relapses observed divided by the total number of patient-years observed. Estimated via Poisson model adjusting for repeated measures correlation
c Relapses were defined as an MS-related inpatient claim with a primary diagnosis of MS or an outpatient MS-related diagnosis and prescription claim for an intravenous steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid ≤ 7 days after the outpatient visit
d Quan–Charlson comorbidities present in at least 10% of any racial/ethnic subgroup
Study Outcomes
ARRs were significantly reduced across all racial/ethnic groups when comparing 12-month pre-index to post-index relapse rates. The mean (95% CI) ARR was reduced from 0.338 (95% CI 0.297–0.385) to 0.252 (95% CI 0.212–0.300) for Black PwMS, 0.311 (95% CI 0.258–0.376) to 0.185 (95% CI 0.138–0.248) for Hispanic PwMS, 0.295 (95% CI 0.212–0.412) to 0.163 (95% CI 0.104–0.256) for Asian PwMS, and 0.299 (95% CI 0.273–0.326) to 0.214 (95% CI 0.182–0.251) for white PwMS (Fig. 2 a). Fig. 2 a ARR 12 months pre-index and post-index and b post-index adjusted ARR ratio vs. white PwMS. ARR calculated as the total number of relapses observed divided by the total number of patient-years observed. Estimated via Poisson model adjusting for repeated measures correlation. Error bars represent the 95% CI. ARR annualized relapse rate, CI confidence interval, MS multiple sclerosis, PwMS people with MS. a Based on Poisson model adjusting for baseline relapse rate, age, sex, and MS severity score. Rate ratio > 1 favors the white racial group
a ARR 12 months pre-index and post-index and b post-index adjusted ARR ratio vs. white PwMS. ARR calculated as the total number of relapses observed divided by the total number of patient-years observed. Estimated via Poisson model adjusting for repeated measures correlation. Error bars represent the 95% CI. ARR annualized relapse rate, CI confidence interval, MS multiple sclerosis, PwMS people with MS. a Based on Poisson model adjusting for baseline relapse rate, age, sex, and MS severity score. Rate ratio > 1 favors the white racial group
After adjusting for racial disparities in MS disease activity and comorbidity burden, the post-index rate ratios for fumarates did not show a significant difference between racial/ethnic subgroups and the white subgroup (Fig. 2 b). The adjusted ARR ratio for Black PwMS was 1.195 (95% CI 0.999–1.428). For Hispanic PwMS, it was 0.839 (95% CI 0.667–1.053), and for Asian PwMS, it was 1.053 (95% CI 0.642–1.710). However, none of these differences reached statistical significance ( p > 0.05 for all).
The adjusted Kaplan–Meier estimated proportion of PwMS who remained relapse-free at 24 months was comparable across all racial/ethnic groups (Fig. 3 ). The estimated proportions of patients remaining relapse-free at 24-months (95% CI) were 77.0% (73.7–80.3%) for Black PwMS, 75.4% (71.0–80.0%) for Hispanic PwMS, 81.7% (73.0–90.3%) for Asian PwMS, and 80.5% (70.0–82.1%) for white PwMS. There were no statistically significant differences in the Black, Hispanic, and Asian groups compared with the white group ( p > 0.05). Fig. 3 Time to first post-index relapse in Black, Hispanic, Asian, and white PwMS. CI confidence interval, MS multiple sclerosis, PwMS people with MS. a Relapses were defined as an MS-related inpatient claim with a primary diagnosis of MS or an outpatient MS-related diagnosis and prescription claim for an intravenous steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid ≤ 7 days after the outpatient visit. b Cox proportional hazards model was adjusted for age, sex, baseline relapses, and MS severity score. p values are based on a modified version of the Pepe and Fleming test comparing the difference in adjusted Kaplan–Meier survival curve versus white (reference group)
Time to first post-index relapse in Black, Hispanic, Asian, and white PwMS. CI confidence interval, MS multiple sclerosis, PwMS people with MS. a Relapses were defined as an MS-related inpatient claim with a primary diagnosis of MS or an outpatient MS-related diagnosis and prescription claim for an intravenous steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid ≤ 7 days after the outpatient visit. b Cox proportional hazards model was adjusted for age, sex, baseline relapses, and MS severity score. p values are based on a modified version of the Pepe and Fleming test comparing the difference in adjusted Kaplan–Meier survival curve versus white (reference group)
From month 0 to month 12, the decline in ALC was less in Black PwMS compared with other racial/ethnic groups (Fig. 4 ). The estimated ALC reduction was 10.3% (95% CI 3.8–16.3%) for Black PwMS, compared with 20.1% (95% CI 14.8–25.1%) for Hispanic PwMS, and 20.4% (95% CI 18.0–22.7%) for white PwMS. The difference in ALC reduction between Black and white PwMS was statistically significant ( p = 0.010), whereas the comparison between Hispanic and white PwMS showed no significant difference ( p = 0.999). There were not enough ALC data available to analyze in the Asian subgroup. Fig. 4 Estimated ALC at baseline and 12 months post-index. Patients included must have had an ALC measure at month 0 and ≥ 1 subsequent ALC measurement. Too few ALC data from Asian people with MS were obtained for the analysis to be meaningful. p values represent the estimated mean trend difference between the specified race group vs. white at the noted time point. Error bars represent the 95% CI. ALC absolute lymphocyte count, CI confidence interval, MS multiple sclerosis
Estimated ALC at baseline and 12 months post-index. Patients included must have had an ALC measure at month 0 and ≥ 1 subsequent ALC measurement. Too few ALC data from Asian people with MS were obtained for the analysis to be meaningful. p values represent the estimated mean trend difference between the specified race group vs. white at the noted time point. Error bars represent the 95% CI. ALC absolute lymphocyte count, CI confidence interval, MS multiple sclerosis
Post-index, the mean MS-related adjusted annualized per-patient per-year HRU rates (95% CI) were 3.57 (3.47–3.67; p = 0.404 vs. white) for Black PwMS; 3.60 (3.48–3.73; p = 0.251 vs. white) for Hispanic PwMS; 3.67 (3.40–3.97; p = 0.554 vs. white) for Asian PwMS; and 3.48 (3.42–3.54; reference group) for white PwMS (Supplementary Material Fig. S1 A). With regard to the HRU rate of 3.57 for Black PwMS, this number indicates that, on average, Black patients interacted with the healthcare system for MS-related reasons 3.57 times per year. Additionally, the HRU rates for all racial/ethnic subgroups were not significantly different from the white patient population.
The mean MS-related adjusted annualized per-patient per-year HCCs (95% CI) post-index were $4559 (3955–5256), $4293 (3625–5084), $3525 (2429–5116), and $4261 (3911–4643) for Black, Hispanic, Asian, and white PwMS, respectively (Supplementary Material Fig. S1 B).
Discussion
The Komodo claims-based database allows for the observation of real-world DMT utilization and assessment of its effectiveness in MS across different racial and ethnic groups. By capturing self-reported race and ethnicity data, we were able to conduct comparative analyses, shedding light on important disparities in healthcare access and outcomes. In this study, Black PwMS were less likely to use commercial insurance plans and were more likely to rely on Medicare/Medicaid compared with Hispanic, Asian, or white PwMS. Additionally, Black PwMS presented with more severe MS at baseline compared with these other groups and were more likely to reside in a state with a higher rate of poverty than white PwMS. Black PwMS had a higher mean MS severity score (7.08 vs. 6.42 in white PwMS) and a greater comorbidity burden (mean Quan–Charlson index of 0.72 vs. 0.56), with higher rates of conditions such as chronic pulmonary disease, diabetes, and congestive heart failure. These observed differences suggest that outcomes are not solely due to biological factors but are also influenced by SDOH—specifically, limited insurance coverage, higher poverty levels, and reduced health literacy—which play a significant role in the elevated baseline disease burden observed in Black PwMS [ 19 ]. Previous studies have shown that minority racial/ethnic groups in the USA may encounter barriers in accessing and utilizing specialty care due to limited or lack of insurance, lower income, lower education levels, and language and computer literacy barriers [ 6 ].
These baseline disparities reflect broader systemic challenges in healthcare that further worsen outcomes in minority patients with MS. In the USA, systemic differences in healthcare access, socioeconomic inequalities, cognitive biases, and racism within the healthcare system may contribute to poorer disease-related outcomes in people from minority racial and ethnic groups [ 20 ]. According to Amezcua et al., Black and Hispanic PwMS often have lower health literacy and face reduced access to specialty care and delays in diagnosis due to systemic and structural racism in healthcare. These factors exacerbate disparities in disease outcomes and access to effective treatments [ 20 ]. Addressing these issues requires systemic interventions, including integrating SDOH data into health records and training providers to reduce biases [ 20 ].
In this study, Black PwMS had a higher baseline Quan–Charlson comorbidity index than other racial/ethnic groups and had fewer days of fumarates exposure post-index than Hispanic, Asian, and white PwMS. This could suggest potential disparities in access to treatments, but it is also possible that other factors contributed to the lower exposure, such as differences in patient preferences, or healthcare provider perceptions. The US Centers for Disease Control and Prevention has emphasized that addressing these barriers first begins with recognizing and bringing awareness to them [ 30 ].
Previous studies have suggested that outcomes in Black PwMS are poorer than those of their non-Black counterparts, although MS has not been adequately studied in minority racial/ethnic groups because of low recruitment of these patients in clinical trials [ 4 – 6 ]. This study included 2150 PwMS from minority racial/ethnic groups and compared outcomes with 4650 white PwMS. The estimated proportion of patients who were relapse-free at 24 months post-index was comparable across all racial/ethnic groups. Despite Black PwMS having a higher pre-index ARR than Hispanic, Asian, and white PwMS, significant reductions in ARR from 12 months pre-index to 12 months post-index were observed across all racial/ethnic groups following fumarate treatment. This indicates that fumarates are effective across racial and ethnic subgroups. These results are consistent with previous studies, including a post hoc analysis of the phase 3 DEFINE and CONFIRM studies, which showed that DMF treatment in Black, Hispanic, and Asian patients with MS was associated with a lower ARR at 2 years and lower 12-week confirmed disability progression compared with placebo treatment [ 14 ]. Furthermore, a retrospective chart review ( N = 390) in patients with relapsing/refractory MS showed that the effectiveness and tolerability of DMF were similar across African American ( n = 69), Hispanic American ( n = 52), and white American patient groups ( n = 261) [ 15 ]. A recent analysis of the phase 4 ESTEEM study found that DMF reduced ARR in Black and Hispanic PwMS, with 5-year outcomes consistent in non-Black and non-Hispanic PwMS [ 17 ]. Additionally, a recent subgroup analysis of Black PwMS from the EVOLVE-MS-1 study supported DRF as an effective treatment option in the Black patient subgroup [ 18 ].
In this study, we compared MS-related HRU and HCC rates in Black, Hispanic, Asian, and white PwMS. All four patient cohorts studied experienced similar annualized rates of healthcare encounters, as well as similar annualized HCCs. These findings indicate that treatment of Black, Hispanic, and Asian PwMS with fumarates provides HRU and HCC rates that were comparable with white PwMS.
The safety profile of DMF treatment in Black and Hispanic PwMS was consistent with the overall population, although there is evidence suggesting a less pronounced reduction in mean lymphocyte counts in Black patients [ 17 ]. In our study, Black PwMS exhibited a smaller decline in ALC at 12 months post-index compared with Hispanic, Asian, and white PwMS. This finding aligns with data from the EVOLVE-MS-1 study, in which Black patients treated with DRF had lower rates of lymphopenia and less pronounced lymphocyte declines than non-Black patients, without the emergence of new safety signals [ 18 ]. However, it is important to note that the observed decline in ALC does not appear to be directly driving the efficacy of the treatment. The relationship between lymphocyte counts and treatment effectiveness is not necessarily causal, and caution should be used when interpreting these ALC results, as they may be independent of efficacy outcomes. Furthermore, as a result of the low number of patients with available laboratory data (Black, n = 53; Hispanic, n = 73; white, n = 329), future research with larger, more racially and ethnically inclusive cohorts is needed to confirm these findings.
This study has several limitations, which are typical of real-world, observational, claims-based studies. These include the lack of randomization, potential coding errors, the inability to confirm reported diagnoses, and challenges in accurately assessing MS disease severity. Relapses were captured only if they led to an outpatient visit, hospital admission, or ER visit, meaning milder relapses not prompting healthcare interactions could be underestimated. Additionally, treatments not billed within 7 days were not captured. The analysis also did not stratify outcomes by patient age, so potential age-related differences in disease course or treatment response could not be evaluated. In the Komodo Health claims database, race and ethnicity were self-reported either as a single designation (e.g., Black or Hispanic, but not both) or as separate fields (e.g., Black race and Hispanic ethnicity). To ensure consistency, Komodo Health consolidates race and ethnicity data into one combined field using the data source of the highest available quality when > 1 is available. Patients reporting their race as “other” were not included. The study also lacked imaging or genomic data and had a limited ALC/laboratory data. Additionally, Expanded Disability Status Scale data were not available to assess higher disability in the Black PwMS group, who were more likely to use Medicare/Medicaid insurance than other racial/ethnic groups. Although the Komodo Health database is one of the largest in the USA, the findings may not be generalizable to other countries. Despite these limitations, analysis of claims data is a valuable tool that has been applied previously to assess DMT treatment patterns, relapses, HRU, and HCCs in the real-world clinical care of patients with MS [ 31 – 33 ].
Conclusions
This large, real-world, claims-based analysis confirmed the benefit of fumarates treatment in 2150 PwMS who self-reported being in a racial/ethnic minority group (Black, Hispanic, or Asian). This is the largest analysis to date of the treatment effects of any individual class of DMT in Black and Hispanic PwMS. Consistent with previous studies, the effectiveness of fumarates was similar across all racial/ethnic groups in this analysis.
Supplementary Information
Below is the link to the electronic supplementary material. Supplementary file1 (PDF 189 KB)
Supplementary file1 (PDF 189 KB)