While initially not thought to have a traditional prodrome, recent multiple sclerosis (MS) literature supports a prodromal period characterized by increased healthcare utilization and diverse nonspecific symptoms. This rise in healthcare-related visits prior to MS diagnosis has been documented, but the potential impact of race and ethnicity remains underexplored. Limited U.S.-based data is available and given the uneven disease burden across populations, this study aims to characterize racial and ethnic differences in the MS prodrome using a large multi-institutional U.S. database. Using the TriNetX U.S. Collaborative Network, we conducted a retrospective matched case-control study using 30,400 MS cases and 30,400 controls. Cases and controls were 1:1 propensity score matched by age, sex, and race along with a second analysis that matched by age, sex, and ethnicity. Prodromal diagnostic categories were defined by ICD chapter, and we examined both the 2–5 and 5–10-year prodromal periods. Odds ratios, 2-sample t-tests and chi-square tests compared case and control groups with the threshold of p<0.05. All diagnostic categories were significantly more prevalent in MS cases than controls across both prodromal windows (p<0.05). In the race-matched analysis, the 2–5-year period revealed odds ratios ranging from 1.56 (neoplasms) to 2.38 (musculoskeletal) and 1.51 (respiratory) to 2.09 (blood) in the 5–10-year period. Musculoskeletal disorders were most prevalent across all cases (45.95%) and controls (26.29%) in the 2–5-year period, with higher prevalence observed in Black and Asian patients compared to White patients. Fewer differences were observed between Hispanic and Non-Hispanic patients, though certain ICD chapters, such as digestive disorders, were significant (Hispanic 31%, Non-Hispanic 28%, p=0.0127, 2–5-year period). Prodromal MS presentations vary significantly across racial and ethnic groups in a diverse U.S. multi-institutional cohort, underscoring the importance of inclusive datasets in prodrome research. This highlights a potential target for early, equitable intervention.
Cortes et al. (Wed,) studied this question.