Abstract Details

Dysregulation in immune regulatory networks is one hallmark of MS pathophysiology, particularly in early relapsing-remitting MS (RRMS). Considering the efficacy of B-cell-depleting therapies, it is of particular interest to explore the impact of ocrelizumab on peripheral immune signatures in a previously treatment-naive cohort.

To explore immunological effects associated with ocrelizumab treatment in the blood of early, previously treatment-naive multiple sclerosis (MS) patients by multiparameter flow cytometry.

Patients (treatment-naive, diagnosis of early-stage RRMS [age 20-56 years; disease duration ≤3 years]) received ocrelizumab 600 mg every 24 weeks. We performed comprehensive characterization of the quantitative changes of circulating T-cells, B-cells, NK-cells, myeloid cells, dendritic cells and their subsets and function in 65 patients by multicolor flow cytometry, measured relative to baseline (pre-infusion) at 24 and 48 weeks after first ocrelizumab infusion. Median cell counts (cells/μL) were evaluated using Kruskal-Wallis test followed by Dunn’s test with Bonferroni correction.

Analysis showed a significant (p<0.0001), stable and virtually complete depletion of all B-cell subsets including naive, memory, transitional and regulatory B-cells after 24 and 48 weeks. A transient increase (p<0.01) in T-cell subset (CD4/CD8 naive, memory, Th1, Th2, Th17, Tregs) counts was observed after 24 weeks that returned back to baseline levels after 48 weeks. This transient increase was accompanied by an increase in CD69 expression levels (CD4/CD8 T-cells) and HLA-DR+ CD8 T-cell counts at Week 24 compared with baseline, which decreased until 48 weeks. Notably, there was no reduction of CD4 and CD8 T-cells and their subsets up to 48 weeks.

Ocrelizumab induced a significant depletion of all B-cell subsets in early-stage RRMS in ENSEMBLE. The changes induced on other lymphocyte subsets remained transient and there was no reduction in T-cell counts and the subsets analyzed as a consequence of B-cell depletion in the first year of treatment.