Disease modifying therapies, serum neurofilament light chain levels, and multiple sclerosis outcomes in Black and Hispanic persons - PROJECT SUMMARY/ABSTRACT Why Black or Hispanic people residing in the US have higher multiple sclerosis (MS)-related disability at younger ages than White people is vastly under-studied. The proposed research will be the first to determine how type and timing of immunomodulatory disease modifying therapies (DMTs) use and/or neuroaxonal injury at MS diagnosis vary by race or ethnicity and how such differences contribute to disparities in long-term prognosis. Recent studies in White persons with relapsing MS (pwRMS) have shown that initiation of highly efficacious DMTs (HETs), but not modestly efficacious DMTs, within 5 years of symptom onset are associated with a reduction in clinically meaningful disability. We hypothesize that the failure to prescribe HETs early in the disease course are primarily responsible for racial and ethnic disparities in MS outcomes. Early initiation of HETs may be particularly important in the subgroup of patients with high levels of serum neurofilament light chain (sNfL, a marker of greater neuroaxonal damage) at diagnosis. High sNfL levels are associated with faster disability progression in White pwRMS–but only when HETs are withheld. If a higher proportion of Black and Hispanic pwMS have high sNfL levels compared with White pwRMS, this could also help explain disparities in MS outcomes–but this has not been studied. The overarching goal of this proposal is to determine whether the failure to prescribe HETs, particularly in the subgroup of patients with greater neuroaxonal damage at diagnosis, is responsible for worse outcomes in Black and Hispanic pwRMS. We will address these goals by conducting: 1) a retrospective cohort study of 2300 newly diagnosed pwRMS including 450 Black and 600 Hispanic individuals identified from the population-based membership of Kaiser Permanente Southern California (KPSC); and 2) a prospective cohort study of the MS Sunshine participants (R01NS075308, PI Dr. Langer-Gould), which includes stored sera samples obtained at MS diagnosis between 2011 and 2014 from 123 Black, 192 Hispanic and 249 White KPSC members. The specific aims of this project are: 1) To determine whether lack of HET use early in the disease course mediates the relationship between race/ethnicity and disability in individuals with newly diagnosed relapsing MS; 2) to determine whether Black or Hispanic pwMS have greater neuroaxonal damage early in the disease course; and 3) to examine whether the lack of HET use in pwRMS with greater neuroaxonal damage early in the disease course is associated with a worse prognosis. Other existing cohorts cannot address these questions because they include predominantly White pwMS. Completion of these aims will: (1) improve our understanding of how inequities in DMT use contribute to worse outcomes in pwRMS; (2) strengthen the evidence for a relationship between early neuroaxonal damage and worse MS prognosis; and (3) help guide targeted interventions to prevent MS- related disability by identifying high-risk subgroups. The results of this study have the potential to guide global MS treatment policies and alleviate racial and ethnic disparities in MS outcomes.
