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Tumor necrosis factor (TNF) inhibitors have changed the therapeutic standard of treatment for patients with rheumatoid arthritis. Despite the efficacy of these agents, a significant proportion of patients demonstrate an inadequate response to one or more TNF inhibitor. In this Viewpoint, Dr Keystone discusses the outstanding issues related to the scientific and clinical rationale for switching TNF inhibitors.
Practical, reliable measures of disease activity and treatment responses for individual patients are needed. Although outcome measures used in randomized controlled trials can be time consuming and impractical in daily practice, the authors of this Review recommend how the findings of trials can be applied to improve practice.
A number of new strategies using biologic therapy for the treatment of rheumatoid arthritis have been developed to target the early stages of disease. In this Review, Dr Keystone highlights the substantial positive effects of these strategies on patient outcomes and discusses the concept that the optimum management of RA involves aggressive early anti-tumor necrosis factor therapy combined with close monitoring of disease progression and modification of ineffective therapeutic strategies.
Disruption of the regulation of the cytokine interleukin 6 can induce inflammatory diseases, many of which have proven refractory to conventional therapies. The clinical use of a humanized monoclonal antibody to block signaling from the interleukin 6 receptor is discussed in this Review.
Tumor necrosis factor inhibitors have been linked with a variety of infections in some patients; of most concern from a public heath perspective is the development of active tuberculosis. In this Review the tuberculosis screening and treatment strategies that should be followed in patients receiving anti-tumor necrosis factor agents are discussed.