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When patients with rheumatoid arthritis fail tumour necrosis factor inhibitors: what is the next step?
  1. Josef S Smolen1,
  2. Michael E Weinblatt2
  1. 1
    Division of Rheumatology, Department of Medicine III, Medical University of Vienna, and Hietzing Hospital, Vienna, Austria
  2. 2
    Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
  1. Josef S Smolen, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; josef.smolen{at}; josef.smolen{at}

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The advent of biological agents in general and tumour necrosis factor (TNF) inhibitors in particular has dramatically changed the outcomes and outlooks for patients with rheumatoid arthritis (RA).1 Not only have they expanded the treatment options in quantitative terms, but their combination with methotrexate (MTX) or other disease-modifying antirheumatic drugs (DMARDs) has also led to a quantitative revolution in the therapeutic response of patients with RA: never before have we experienced so profound effects with American College of Rheumatology (ACR) 50% improvement responses being achieved by 40–60% of the patients, ACR70 responses by 20–40%, and remission having become an achievable goal.2 The efficacy of these therapies relates to all characteristics of RA: disease activity, joint damage and physical function. Alas, these results also reveal that up to 60% of patients with RA do not reach a degree of 50% improvement and, while most patients treated in clinical care who fail these therapies are primary non-responders, some experience reactivation of their disease after an initial major improvement.3

In general, TNF inhibitors are used in patients with RA in whom at least one DMARD, usually MTX, has shown insufficient efficacy.4 …

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