Greater Composite Confirmed Disability Progression in Non-Hispanic Black and Hispanic or Latino Individuals with Relapsing Multiple Sclerosis: Analysis of Self-reported Identity and Genetic Ancestry in the OPERA I and II Trials

Abstract Text:

Background: Individuals of underrepresented racial and ethnic backgrounds with multiple sclerosis (MS) may experience a more severe disease course. Ocrelizumab is a B-cell–depleting therapy approved for the treatment of MS.

Objectives: To assess whether persons with relapsing MS (pwRMS) self-identifying as non-Hispanic Black (NHB) or Hispanic/Latino (HL) exhibit differences in disability progression vs those identifying as non-Hispanic White (NHW) and whether such differences are confirmed by genetic-ancestry analysis.

Methods: We examined longitudinal outcomes in pwRMS who self-reported as NHB (n=65), HL (n=213) or NHW (n=1350) in the pivotal ocrelizumab RMS trials (NCT01247324, NCT01412333). Genetic-ancestry for consenting participants (n=1138) was determined using ADMIXTURE, with 1000 Genomes Project data used for reference-populations. Self-reported identity or genetic-ancestry and 24-week composite-confirmed-disability-progression (cCDP) risk were evaluated using time-to-event analysis. Differences in CD19+ B-cell levels between subgroups were assessed using the Mann-Whitney U-test.

Results: In the comparator interferon treatment group, pwRMS self-identifying as NHB or HL showed greater risk for 24-week cCDP than NHW individuals (hazard ratio [HR] [95% CI] NHB: 3.0 [1.4–6.5]; P=0.006; HL: 2.3 [1.6–3.4]; P< 0.001). Genetic analyses confirmed the association between proportion of African (HR, 4.4 [1.7–11.2]; P< 0.001) or admixed-American (HR, 5.8 [2.7–12.4]; P=0.002) ancestry and greater risk for cCDP. Baseline CD19+ B-cell levels were higher in NHB or HL pwRMS and were reduced with ocrelizumab treatment in all subgroups (all, P< 0.001).

Conclusions: NHB and HL pwRMS showed greater risk for cCDP while receiving interferon treatment. Genetic analysis confirmed the higher progression risk in pwRMS with African or admixed-American ancestry.