title: The pathogenesis of rheumatoid arthritis: new insights from old clinical data?
abstract: Despite their different targets, biologic agents used for blockade of TNF and IL-6, inhibition of T-cell co-stimulation and B-cell depletion all have similar beneficial effects on the outcome of rheumatoid arthritis (RA). This observation raises questions as to whether the targets of these therapies might all be involved in a common pathogenetic pathway. However, blockade of TNF and IL-6 has a similar inhibitory effect on joint damage progression in patients with either early or late disease. In comparison, B-cell depletion and inhibition of T-cell co-stimulation seem to have a somewhat delayed effect on joint damage (compared with cytokine inhibition), which suggests that these approaches affect upstream pathogenetic events. This article discusses these disparities and presents hypotheses as to whether clinical trial data can be used to determine at which point a biologic agent might interfere with the pathogenetic cascade in RA.
authors.affiliation: Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. josef.smolen@meduniwien.ac.at
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.forename: Daniel
authors.initials: D
authors.lastname: Aletaha
authors.forename: Kurt
authors.initials: K
authors.lastname: Redlich
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D001691:Biological Therapy / Q000379:methods*; D004195:Disease Models, Animal; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology; D000093242:Interleukin-6 Inhibitors
chemical_list: D007166:Immunosuppressive Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human