Anti-CD20 therapies for multiple sclerosis: current status and future perspectives

Abstract

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease affecting the central nervous system (CNS), often characterized by the accumulation of irreversible clinical disability over time. During last years, there has been a dramatic evolution in several key concepts of immune pathophysiology of MS and in the treatment of this disease. The demonstration of the strong efficacy and good safety profile of selective B-cell-depleting therapies (such as anti-CD20 monoclonal antibodies) has significantly expanded the therapeutic scenario for both relapsing and progressive MS patients with the identification of a new therapeutic target. The key role of B cells in triggering MS disease has been also pointed out, determining a shift from the traditional view of MS activity as largely being ‘T-cell mediated’ to the notion that MS-related pathological processes involve bi-directional interactions between several immune cell types, including B cells, both in the periphery and in the CNS. This review provides an updated overview of the involvement of B cells in the immune pathophysiology and pathology of MS. We summarize the rationale regarding the use of anti-CD20 therapies and the results of the main randomized controlled trials and observational studies investigating the efficacy and safety profile of rituximab, ocrelizumab, ofatumumab and ublituximab. Suggestions regarding vaccinations and management of MS patients during COVID-19 pandemic with anti-CD20 therapies are also discussed. Finally, therapies under investigation and future perspectives of anti-CD20 therapies are taken into consideration.

Remission of idiopathic retroperitoneal fibrosis by ofatumumab as a disease-modifying therapy for multiple sclerosis

“…Recently, the involvement of CD20-positive lymphocytes in the development of MS has been identified, and anti-CD20 mAb such as ofatumumab has become the consensus therapy [ 6 , 7 ]. On the other hand, it is also evident that the pathogenesis of retroperitoneal fibrosis is strongly based on CD20+ lymphocytes [ 3 ], which was also shown in the perivascular CD20+ lymphocytes of the present case's retroperitoneal fibrosis.…”

Antibody Therapies for Progressive Multiple Sclerosis and for Promoting Repair

“…In addition to the therapeutic development of additional and well-established antibodies, with so-called small molecules, a new option of treating PwPMS is emerging. One possible therapeutic approach is the inhibition of Bruton's tyrosine kinase (BTK) [88]. BTK regulates the activation, proliferation, and differentiation of B cells into plasma cells [89,90].…”

Long-term immunological consequences of anti-CD20 therapies on humoral responses to COVID-19 vaccines in multiple sclerosis: an observational study

“…Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS) presumably mediated by auto-aggressive lymphocytes with encephalitogenic potential. 1 – 4 In fact, therapies that target B cells have demonstrated high efficacy in reducing cerebral inflammation in people with MS (pwMS). 5 , 6 Anti-CD20 therapeutics selectively target B cells and induce a profound, continuous depletion of peripheral B cells based on a 6-monthly dosing interval.…”