title: [Methotrexate as combination partner of TNF inhibitors and tocilizumab: what is reasonable from an immunological viewpoint?].
abstract: BACKGROUND
  The prognosis of rheumatoid arthritis has been substantially improved by the treatment with biologics; however, it is still unclear which combination of biological and conventional disease-modifying antirheumatic drugs (DMARDs) is optimal to achieve remission as in clinical trials biologics were mainly studied in combination with methotrexate or as monotherapy. There are, however data that the efficacy of tumor necrosis factor (TNF) inhibitors is better in combination with methotrexate, whereas the efficacy of tocilizumab is optimal even as a monotherapy. In this article the differing dependence of TNF inhibitors and of tocilizumab on the combination with methotrexate is explained from the viewpoint of an immunologist.
  
  
  METHODS
  A selective search and evaluation of the literature were carried out in relation to the mechanism of action of TNF inhibitors, tocilizumab and methotrexate in rheumatoid arthritis.
  
  
  CONCLUSIONS
  Methotrexate mainly targets the activation of T and B lymphocytes and TNF inhibitors suppress monocytes and myeloid dendritic cells. Tocilizumab corrects the errant activation and differentiation of T and B lymphocytes and in addition inhibits monocytes, dendritic cells and neutrophils. Therefore, TNF inhibitors and methotrexate act optimally only in combination to exert an effect on all components of the cellular immune system in rheumatoid arthritis. In contrast, tocilizumab has a broad mode of action even in monotherapy.
authors: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Deutschland. Witte.torsten@mh-hannover.de
authors: T
authors: T
authors: Witte
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D004359:Drug Therapy, Combination / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008727:Methotrexate / Q000008:administration & dosage*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; C502936:tocilizumab; D008727:Methotrexate