Abstract
The goal of therapy of rheumatoid arthritis is to achieve a remission or at least low disease activity. TNF inhibitors induce high remission rates only in combination with methotrexate, whereas the efficacy of tocilizumab is optimal even as a monotherapy. In this article, the differing dependence of the biological drugs on methotrexate is explained from the viewpoint of an immunologist. A selective search and evaluation of the literature was performed with regard to the mode of action of TNF inhibitors, tocilizumab and methotrexate in rheumatoid arthritis. Methotrexate primarily inhibits the activation and proliferation of lymphocytes. TNF inhibitors suppress monocytes and myeloid dendritic cells, and tocilizumab has a broader activity and is directed against both the lymphoid as well as the myeloid compartment. In view of the broad mode of action of tocilizumab, it can be explained why this drug, in contrast to TNF inhibitors, is acting optimally even in monotherapy.
Highlights
Since the introduction of biologics into the treatment of rheumatoid arthritis (RA), patients’ symptoms have been significantly reduced and the process of joint destruction markedly decelerated
The autoimmune aspect of the disease begins many years before overt arthritis occurs. In this ‘pre-arthritis’ phase, the autoantibodies rheumatoid factor (RF) and anti-citrullinated peptide/protein antibodies (ACPA) can usually be detected [6]; even on biopsy, no inflammatory changes can be found in the joint [7]
TNF-α is predominantly produced by monocytes/macrophages, as well as by T cells, and activates, for example, macrophages and endothelial cells, after binding to the TNF receptor (CD120), which is expressed on multiple cells
Summary
The initiation of RA is facilitated by a genetic predisposition. In addition, the probability of developing RA is influenced by environmental factors such as smoking, alcohol and nutrition. The autoimmune aspect of the disease begins many years before overt arthritis occurs In this ‘pre-arthritis’ phase, the autoantibodies rheumatoid factor (RF) and anti-citrullinated peptide/protein antibodies (ACPA) can usually be detected [6]; even on biopsy, no inflammatory changes can be found in the joint [7]. Antigen-presenting cells in the joint loaded with an autoantigen probably move to the central lymphatic organs and activate T cells there They migrate back to the joints, along with circulating immune cells. The formation of cytokines such as TNF-α and IL-6 at the site of inflammation leads to activation of the endothelium cells in newly formed vessels and to an increase in adhesion receptors such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) [10] This further increases the adhesion and migration of leucocytes and lymphocytes from the blood into the inflamed joints [11]
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