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Ocrelizumab Depletes CD20? T Cells in Multiple Sclerosis Patients.

ABSTRACT: Ocrelizumab, a humanized monoclonal anti-CD20 antibody, has shown pronounced effects in reduction of disease activity in multiple sclerosis (MS) patients and has recently been approved for the treatment of patients with relapsing MS (RMS) and primary progressive MS (PPMS). CD20 is mainly expressed by B cells, but a subset of T cells (CD3?CD20? T cells) also expresses CD20, and these CD20? T cells are known to be a highly activated cell population. The blood of MS patients was analyzed with multicolor flow cytometry before and two weeks after treatment with ocrelizumab regarding the phenotype of peripheral blood mononuclear cells. CD20-expressing CD3? T cells were found in blood samples of all MS patients, accounted for 2.4% of CD45? lymphocytes, and constituted a significant proportion (18.4%) of all CD20? cells. CD3?CD20? T cells and CD19?CD20? B cells were effectively depleted two weeks after a single administration of 300 mg ocrelizumab. Our results demonstrate that treatment with ocrelizumab does not exclusively target B cells, but also CD20? T cells, which account for a substantial amount of CD20-expressing cells. Thus, we speculate that the efficacy of ocrelizumab might also be mediated by the depletion of CD20-expressing T cells.

SUBMITTER: Gingele S

PROVIDER: S-EPMC6356421 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Ocrelizumab Depletes CD20⁺ T Cells in Multiple Sclerosis Patients.

Gingele Stefan S Jacobus Thais Langer TL Konen Franz Felix FF Hümmert Martin W MW Sühs Kurt-Wolfram KW Schwenkenbecher Philipp P Ahlbrecht Jonas J Möhn Nora N Müschen Lars H LH Bönig Lena L Alvermann Sascha S Schmidt Reinhold E RE Stangel Martin M Jacobs Roland R Skripuletz Thomas T

Cells 20181228 1

Ocrelizumab, a humanized monoclonal anti-CD20 antibody, has shown pronounced effects in reduction of disease activity in multiple sclerosis (MS) patients and has recently been approved for the treatment of patients with relapsing MS (RMS) and primary progressive MS (PPMS). CD20 is mainly expressed by B cells, but a subset of T cells (CD3⁺CD20⁺ T cells) also expresses CD20, and these CD20⁺ T cells are known to be a highly activated cell population. The blood of MS patients was analyzed with multi ...[more]

PMID: 30597851

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Project description:Data regarding effectiveness and safety of ocrelizumab in the post-marking setting are lacking. The aim of our study was to provide effectiveness and safety data of ocrelizumab treatment in patients with relapsing-remitting (RR-) and progressive multiple sclerosis (PMS) and to evaluate clinical and immunological predictors of early treatment response. In this single-center prospective observational study, we investigated effectiveness outcomes (time-to-confirmed disability worsening, time-to-first relapse, time-to-first evidence of MRI activity and time-to-first evidence of disease activity), clinical and immunological predictors of early treatment response, and incidence of adverse events (AEs). One hundred and fifty-three subjects were included (93 RRMS; 84 females). Median follow-up was 1.9 (1.3-2.7). At 2-year follow-up (FU), disability worsening-free survival were 90.5%, 64.7%, and 68.8% for RRMS, primary-progressive MS (PPMS), and secondary-progressive MS (SPMS) patients, respectively. At 2-year FU, 67.1%, 72.7%, and 81.3% of patients with RRMS, PPMS, and SPMS were free of MRI activity, with NEDA-3 percentages of 62.1%, 54.6%, and 55.1%, respectively. Lower baseline EDSS was independently associated with a reduced risk of disability worsening (HR(95%CI) = 1.45(1.05-2.00), p = 0.024) and previous treatment exposure was independently associated with increased probability of radiological activity (HR = 2.53(1.05-6.10), p = 0.039). At 6-month FU, CD8 + cell decrease was less pronounced in patients with inflammatory activity (p = 0.022). Six patients (3.9%) discontinued ocrelizumab due to severe AEs. Our findings suggest that ocrelizumab is an effective treatment in real-world patients with RRMS and PMS, with a manageable safety profile. Better outcomes were observed in treatment-naïve patients and in patients with a low baseline disability level. Depletion of CD8 + cells could underlie early therapeutic effects of ocrelizumab.

Dataset Information

Ocrelizumab Depletes CD20? T Cells in Multiple Sclerosis Patients.

Publications

Ocrelizumab Depletes CD20⁺ T Cells in Multiple Sclerosis Patients.

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