To assess the impact of ocrelizumab (OCR) treatment on blood B cells and B-cell subsets in patients with relapsing multiple sclerosis (RMS) from the OPERA I (NCT01247324) and OPERA II (NCT01412333) trials.

B cells play a pathogenic role in MS, with certain B-cell subsets (memory, plasmablast/plasma cells) elevated in cerebrospinal fluid (CSF) vs blood. B cells, including those in CNS lymphoid aggregates, have been implicated in chronic inflammation potentially responsible for disease progression. OCR depletes CD19⁺ B cells in blood and CSF, reduces CSF IgG synthesis, and reduces disease activity and progression in patients with RMS.

Total B-cell (CD19⁺) and B-cell subset (mature naive [CD19⁺/IgD⁺/CD27⁻], memory B cell [CD19⁺/CD27⁺/CD38^low], double-negative memory B cell [CD19⁺/IgD⁻/CD27⁻] and plasmablast/plasma cell [CD19⁺/CD27⁺⁺/CD38⁺⁺]) levels were measured via flow cytometry in whole blood samples in 1,645 RMS patients at study baseline and before each OCR infusion (weeks 24, 48, 72, 96). Median cell count (cells/μL) was calculated across timepoints, and the proportion of patients with median B-cell count below the lower limit of quantification was assessed for each B-cell subtype across treatment arms and mean OCR exposure quartiles (measured as mean OCR concentration over treatment duration).

Total B cells and all B-cell subsets were significantly depleted by OCR (p<0.005) and progressively depleted following repeated dosing. Patients in the upper quartiles of OCR exposure had a higher proportion of B-cell/B-cell–subset depletion when compared with patients in the lowest quartile (all p<0.005). CD19⁺/CD27⁺⁺/CD38⁺⁺ cells, mainly plasmablasts in blood, had the lowest relative reduction, and mature naive B cells had the greatest.