title: Methotrexate as combination partner of TNF inhibitors and tocilizumab. What is reasonable from an immunological viewpoint?
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.
authors.affiliation: Clinic for Immunology and Rheumatology, Medical University of Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany, Witte.Torsten@mh-hannover.de.
authors.forename: Torsten
authors.initials: T
authors.lastname: Witte
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D007107:Immune System; D007249:Inflammation / Q000378:metabolism; D007596:Joints / Q000473:pathology; D008727:Methotrexate / Q000008:administration & dosage*; D009000:Monocytes / Q000187:drug effects; D053245:RANK Ligand / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D053245:RANK Ligand; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C502936:tocilizumab; D008727:Methotrexate