Ocrelizumab is a humanized monoclonal antibody designed to bind to the CD20 molecule, resulting in a rapid depletion of B-cells; however, it has been shown that lymphocyte subpopulations other than B-cells are affected by the drug. To review the effects of ocrelizumab on circulating lymphocytes and identify candidate biomarkers to predict and monitor treatment response. A literature search for the most relevant articles from 2006 to 2022 was conducted in PubMed and Scopus. The effect of ocrelizumab on the peripheral immune system goes beyond B-cells; it also depletes T CD20 + lymphocytes. Further, ocrelizumab reshapes the T-cell response toward a low inflammatory profile and induces an increase in T CD8 + regulatory cell percentage. A higher Body Mass Index and higher B-cell count at baseline have been associated with early B-cell reappearance. Serum neurofilament light chain reduction has been associated with treatment response. Ocrelizumab treatment exerts a broad immunomodulatory effect and may be tailored based on patients’ clinical and biological profiles.
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