During the last two decades fundamental changes have taken place in the treatment of patients with rheumatoid arthritis (RA). The effective establishment of methotrexate as the anchor drug and the introduction of new drugs, in particular anti-tumor necrosis factor (TNF) alpha blockers and the novel biologics have made the goal of remission feasible for plenty of RA patients. However, almost 14-38% of patients do not respond to first-line anti-TNF-alpha treatment at all and as many as 40% discontinue these drugs within a year and 50% within 2 years. Currently, no recommendations exist as regards the treatment of RA patients after TNF-alpha-antagonist failure. In this review the issue of anti-TNF-alpha therapy failure is discussed. Further, the various options for overcoming the apparent failure are explored according to evidence from the published literature.
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