Chapter 12 - Clinical efficacy of anti-CD20 antibodies in autoimmune diseases

Abstract

Anti-CD20 monoclonal antibodies such as Rituximab, Ofatumumab, Obinutuzumab, Ocrelizumab, Ublituximab, and Veltuzumab are widely used to treat several disorders including autoimmune diseases. Their role is to achieve B-cell depletion mainly through Fc-dependent effector functions. The main molecular mechanisms considered responsible for CD20+ cell elimination by anti-CD20 monoclonal antibodies are antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), direct anti-B-cell effects through apoptosis or other cell death pathways. Several clinical trials of these agents have been accomplished in different autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, pemphigus vulgaris, systemic sclerosis, and systemic lupus erythematosus. Recently, the efficacy of anti-CD20 monoclonal antibodies in immune deregulation diseases was also reported. As a first-generation anti-CD20 monoclonal antibody which was approved in 1997, rituximab became an extraordinarily secure choice for the control of autoimmune and lymphoproliferative manifestations associated with primary immunodeficiencies in particular immune thrombocytopenic purpura, autoimmune hemolytic anemia, and granulomatous disease in subjects who suffered from common variable immunodeficiency, and autoimmune lymphoproliferative syndrome patients. In total, anti-CD20 monoclonal antibody therapies are generally well tolerated, but some precautions must be taken to ensure their safety. There is some concern about their adverse events, including hypogammaglobulinemia, which increases the risk of infection. Currently, more investigations are ongoing in order to study the long-term safety profile and reduce severe adverse events.