scholarly journals Stable multiple sclerosis patients on anti-CD20 therapy should go on extended interval dosing: NO

2022 ◽  
pp. 135245852110644
Author(s):  
Zoé LE van Kempen ◽  
Laura Hogenboom ◽  
Joep Killestein
2021 ◽  
pp. 135245852110559
Author(s):  
Jun-ichi Kira ◽  
Jin Nakahara ◽  
Denis V Sazonov ◽  
Takayoshi Kurosawa ◽  
Isao Tsumiyama ◽  
...  

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, has been developed as a treatment for relapsing multiple sclerosis (RMS) which can be self-administered at home. Objective: To investigate the efficacy and safety of ofatumumab in RMS patients from Japan and Russia. Methods: APOLITOS included a 24-week, double-blind, placebo-controlled core-part followed by an open-label extension-part. Patients were randomized (2:1) to subcutaneous ofatumumab 20 mg or placebo. Primary outcome was the number of gadolinium-enhancing (Gd+) T1 lesions per scan over 24 weeks. Results: Sixty-four patients were randomized (ofatumumab, n = 43; placebo, n = 21). Primary endpoint was met; ofatumumab reduced Gd + T1 lesions versus placebo by 93.6% ( p < 0.001) and the results were consistent across regions (Japan/Russia). Ofatumumab reduced annualized T2 lesion and relapse rate versus placebo by week 24. Both groups showed benefit from ofatumumab in the extension-part. Incidence of adverse events was lower with ofatumumab versus placebo (69.8% vs 81.0%); injection-related reactions were most common. No deaths, opportunistic infections, or malignancies were reported. Conclusion: Ofatumumab demonstrated superior efficacy versus placebo, with sustained effect through 48 weeks in RMS patients from Japan/Russia. Switching to ofatumumab after 24 weeks led to rapid radiological and clinical benefits. Safety findings were consistent with pivotal trials.


2020 ◽  
Author(s):  
Vinícius de Oliveira Boldrini ◽  
Raphael Patrício da Silva Quintiliano ◽  
Adriel dos Santos Moraes ◽  
Carla Stella ◽  
Ana Leda Figueiredo Longhini ◽  
...  

Abstract Background Recently, the success of anti-CD20 monoclonal antibody therapy brought a new light over the role of B cells in multiple sclerosis (MS) pathogenesis. Due to the expression pattern of CD20 during B cells ontogeny, this role seems to be extended beyond the antibodies' production and secretion. Therefore, here we investigated whether not only classical cytotoxic CD8+ T lymphocytes but also non-classical cytotoxic B cells may occur in the peripheral blood from relapsing-remitting MS (RRMS) patients. Methods 104 RRMS patients during different treatment and 58 healthy donors were studied. CD19, GzmB, Runx3 and CD49d expression was assessed by flow cytometry analyses. Results Patients treated with Natalizumab (NTZ) showed an increased percentage of CD8+GzmB+ when compared to other MS therapies, untreated RRMS patients and healthy volunteers. Similarly, and unexpected, massive cytotoxic behavior of B cells CD19+GzmB+ was observed in RRMS patients during Fingolimod (FTY) and NTZ therapies when compared to Glatiramer, Interferonβ, untreated MS patients and healthy donors. Conclusions During different MS treatments, B cells exhibit cytotoxic behavior resembling CD8+ T lymphocytes. This data suggest a possible involvement of “cytotoxic” B cells during MS pathology. Monitoring cytotoxic subsets might become an available marker for the risk of relapses and even for accessing therapeutic effectiveness in MS patients.


2020 ◽  
Vol 9 (12) ◽  
pp. 4067
Author(s):  
Nora Möhn ◽  
Franz F. Konen ◽  
Refik Pul ◽  
Christoph Kleinschnitz ◽  
Harald Prüss ◽  
...  

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic is a challenge for all participants in the healthcare system. At the beginning of the pandemic, many physicians asked themselves what risk their patients, especially those with chronic diseases, were exposed to. We present an overview of all patients with multiple sclerosis (MS) and SARS-CoV-2 infection published in the literature so far. In total, there are publications on 873 SARS-CoV-2 positive MS patients and information on the outcome can be given for 700 patients. With regard to the different disease modifying therapies (DMTs), by far the most cases were described under anti-CD20 treatment (n = 317). The mortality rate of all MS patients was 4% and a further 3% required invasive or non-invasive ventilation. When looking at the severe and fatal cases, it is particularly noticeable that patients without DMTs, with previous cardiovascular diseases, or with a severe degree of disability are at risk. Immunosuppressive therapy itself does not appear to be a substantial risk factor. Rather, it is reasonable to assume that the therapies could be protective, either directly, by mitigating the cytokine storm, or indirectly, by reducing the disease activity of MS.


2020 ◽  
Vol 44 ◽  
pp. 102306 ◽  
Author(s):  
Virginia Meca-Lallana ◽  
Clara Aguirre ◽  
Beatrizdel Río ◽  
Laura Cardeñoso ◽  
Teresa Alarcon ◽  
...  

Cells ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 12 ◽  
Author(s):  
Stefan Gingele ◽  
Thais Jacobus ◽  
Franz Konen ◽  
Martin Hümmert ◽  
Kurt-Wolfram Sühs ◽  
...  

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.


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