Immunobiological Therapies in Rheumatoid Arthritis: Mechanisms of Action and Future Perspectives

Rheumatoid Arthritis (RA) is a disease with no specific cause involving several cell mechanisms. The treatment for this disorder involves several drugs with different purposes. The most current treatments implicate immunobiological, which can be used in monotherapy or combined with first-line drugs. New researches are underway for increasingly effective treatments, as there are unknown aspects of RA’s pathophysiology that can be a source for new therapies. Immunobiological therapies are attributed as substances of protein origin, such as human or animal-origin antibodies, which are obtained through techniques derived from biotechnology. Immunobiological therapy is a treatment used to combat inflammatory and autoimmune diseases, among them RA. The RA results from the action of self-reactive T and B cells, which leads to synovitis, cell infiltration, and a confusing process of bone destruction and remodeling. Several therapeutic antigenic targets have been described in recent years based on the participation of these diverse elements in the pathophysiology of different diseases. Its applicability in the immune system arises through several mechanisms, such as blockage or stimulation of immune pathways, resulting in better disease evolution. The first monoclonal antibodies used were of murine origin, followed by genetically modified chimeric antibodies, humanized antibodies, and fully human molecules. With the advancement in this field, several therapies are emerging and showing to be effective in significantly improving the patient’s condition, with cases where the remission of the disease is observed. Among the primary therapies, we can mention those that modulate and deplete B cells, blockers of costimulatory pathways, and anti-inflammatory cytokines such as IL-6 and TNF. Belimumab is a human monoclonal antibody to the soluble B lymphocyte stimulator (BLsY) that blocks the interaction of this stimulator to B cell receptors, thus promoting the depletion of activated B cells. On the other hand, Rituximab is a chimeric monoclonal antibody (murine/human) that acts against the CD20 molecule expressed on the surface of B lymphocytes. B cells covered with anti-CD20 antibodies undergo cell-mediated cytotoxicity, are targeted by the complement system and suffer apoptosis. Similarly, Abatacept is a human fusion protein composed of an extracellular domain of cytotoxic T lymphocyte-associated antigen (CTLA-4) and the Fc portion of immunoglobulin G1 (IgG1). It is a selective modulator of the second signal for activation of T lymphocytes and acts by preventing the interaction of CD80/CD86 of APCs with CD28 of T cells, though its effect in other immune pathways is still being clarified. Another immunobiological drug of great applicability for RA therapy is Tocilizumab, a monoclonal antibody anti-IL6. Many studies report significant improvements in patients and the reduction of autoantibody titers. Finally, Infliximab is a chimeric monoclonal antibody composed of human and mouse peptides, whose application in patients with anti-TNF MII indicates improvement in muscle strength and reduction of muscle enzymes. The objective of this chapter is to review the concepts of immunobiological therapies based on the use of antibodies, as well as to discuss the basis of the immune response with a focus on relevant therapeutic targets. In addition, the chapter will detail the molecular mechanisms by which such elements directly interfere in the pathophysiology of several diseases, with a primary focus on rheumatoid arthritis, promoting relevant improvements in different treatments.