Ocrelizumab for the Treatment of Multiple Sclerosis: Safety, Efficacy, and Pharmacology

Abstract

The success of selective B-cells depleting therapies, as the anti-CD20 antibodies, in patients with multiple sclerosis (MS) has confirmed that B-cells are critical in the immune pathogenesis of the disease. Ocrelizumab, a humanized monoclonal antibody that selectively targets CD20+ B-cells, profoundly suppresses acute inflammatory disease activity, representing a highly effective therapy for relapsing-remitting multiple sclerosis (RRMS). It is also the first proven therapy able to slow disability progression in primary progressive multiple sclerosis (PPMS), particularly in patients with signs of acute radiological activity before being enrolled. Effectiveness has widely been demonstrated in randomized clinical trials (RCTs), and recently confirmed in open-label extension trials. Here, we review the role of B-cells in MS, the mechanism of action of ocrelizumab, its pharmacokinetics and pharmacodynamics, and the clinical data supporting its use, as well as safety data. We focus on issues related to the maintenance of immunocompetence, essential to ensure an immune response to either a primary infection or a vaccination. Lastly, we discuss about the possible role of ocrelizumab as an exit strategy from natalizumab-treated patients at risk of developing multifocal progressive leukoencephalopathy. In view of using ocrelizumab chronically, collecting long-term safety data and finding strategies to minimize adverse events will be extremely relevant.

Mapping the Therapeutic Options for Multiple Sclerosis in Brazil: A Comprehensive Analysis

“…Ocrelizumab interacts with the CD20 antigen on B lymphocytic cells, resulting in antibody-dependent cytotoxicity and complement-mediated lysis. Although the precise mechanisms through which ocrelizumab exerts its effect in multiple sclerosis remain unknown, it induces B cell depletion, which is believed to be involved in the pathogenesis of the disease, influencing cytokine regulatory processes, antigen presentation, and autoantibody production [90,91].…”

Multiple Sclerosis: Current Knowledge of the Pathology and Use of Monoclonal Antibodies as a Promising Therapy

“…Besides, infections due to induced immunosuppression have been reported 105,112 , so the drug should be avoided in severely immunosuppressed or cancer patients 113 . Moreover, it is necessary to perform a test for hepatitis B and C before the first dose, as it has been associated with reestablishing its viral replication (suboptimal humoral immune response) 114, 115 .…”

Updates and Advances in Multiple Sclerosis Neurotherapeutics

“…Rituximab, a chimeric monoclonal antibody targeting CD20 (which is primarily expressed on B lymphocyte surfaces and a minority of T lymphocytes), has been used off-label to treat patients with MS [ 88 ]. Anti-CD20 monoclonal antibodies exert their beneficial effects in MS through rapid and effective elimination of circulating B lymphocytes [ 89 ]. Despite rituximab’s widespread use in MS, no large phase III trials have examined its effects in relapsing forms of MS, but this area is unlikely to be pursued in the setting of multiple newly developed anti-CD20 therapies.…”

“…There is an apparent association between decreased IgG levels and rates of serious infections, but the type, severity, duration and outcomes of these infections are similar to those in the overall ocrelizumab and general MS populations [ 94 ]. Other risk factors such as age, body mass index, other comorbidities, prior DMTs and disability may also be influential [ 89 ]. Overall, the significance of hypogammaglobulinemia and long-term use of anti-CD20 therapies for long-term safety risks is not well understood and deserves further exploration.…”