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Until recently, in the pathogenesis of Multiple Sclerosis (MS), the contribution of B cells has been largely underestimated, and the disease was considered a T-cell-mediated disorder. However, newer evidence shows that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and through the cross regulation of T-helper cells. As B cells express the surface molecule CD20 at all points of differentiation, it provides a specific target for monoclonal antibodies, and the development and clinical testing of anti-CD20 antibody treatments for MS have been successful. After some observations, some small clinical trials found positive effects for the first anti-CD20 therapeutic rituximab in MS; newer agents have been specifically evaluated, resulting in the development of ocrelizumab and ofatumumab. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, was approved in March 2017 by the Food and Drug Administration (FDA) and is also the first proven therapy to reduce disability progression in primary progressive MS. This is particularly significant considering that disease-modifying treatment options are few for both primary and secondary progressive MS. Ofatumumab, a fully human anti-CD20 monoclonal antibody, that binds a distinct epitope, has been further investigated in phase 3 trials for relapsing forms of MS. In this review, we discuss in detail these two anti-CD20 agents and their advent for treatment of MS.

The treatment of multiple sclerosis (MS) has changed over the last 20 years. All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms. The most common injectable disease-modifying therapies in RRMS include β-interferons 1a or 1b and glatiramer acetate. However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year. Herein, we go back to the basics to understand the immunopathophysiology of MS to gain insights in the development of new improved drug treatments. We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumb, ocrelizumab, alentuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS., Competing Interests: V.A. is supported by Vianex S.A. Greece in developing immunotherapeutics against MS; N.D. is supported under VU-Vianex contract 2 (specific task agreement MS immunotherapeutics) in developing immunotherapeutics against MS; J.M. is head of the scientific advisory board of ELDrug a spin off company of Vianex S.A.; M.-E.A. works for Vianex S.A. Greece; T.T. has an association with Vianex S.A. Greece in relation to supporting his research; M.K. is an employee of Novartis (Hellas) Greece; M.d.C. declares no conflicts of interest. The review represents a detailed literature search in the areas of drugs and treatments against MS with no bias towards immunotherapeutics developed by Vianex S.A.