TNF-INHIBITOR THERAPY IN RHEUMATOID ARTHRITIS Rheumatoid arthritis (RA) is a systemic inflammatory disorder and the most common form of inflammatory arthritis. It has a substantial societal impact in terms of cost, disability, and lost productivity. RA signs and symptoms in early disease are driven by inflammation and include joint pain, joint stiffness, and joint swelling. Untreated, the disease can affect many organs throughout the body, but the joints are usually most severely affected. Although there is impressive knowledge on the pathology of RA, the cause of RA remains unknown. Presently, the hypothesis that the combination of a susceptible genetic profile in combination with external factors triggers the onset of the inflammatory disease is widely accepted. The prevalence of RA is estimated around 1%. The course of the disease is variable if untreated. Approximately 15% to 20% of patients have a relatively good prognosis. In other patients, a more progressive disease course is present. In some patients a rapid course of increasing joint damage is seen (1,2). Several auto-antibodies have been found in RA, especially rheumatoid factor (RF) and anticitrullinated peptide antibodies (ACPA). Although RF is the 'classic' auto-antibody in RA, it can be found also in healthy people and other types of immune mediated diseases. The sensitivity and specificity of RF for RA are up to 70% and 85%, respectively. ACPA is slightly more specific for RA (sensitivity up to about 70% and specificity up to 95%) and thought to play a role in the pathogenesis of the disease (3). Therapeutic strategies in RA have been changed in the last decades. In the 1970s, it was common to start with Aspirin or non-steroidal anti-inflammatory drugs (NSAIDs). In those days, available disease-modifying anti-rheumatic drugs (DMARDs) were only initiated once radiographic damage had been demonstrated (4). Especially outside Europe, patients were frequently treated with corticosteroids only. Over the last decades of the last century, conventional DMARDs became available, such as anti-malaria (hydroxychloroquine), sulphasalazine, oral gold, intramuscular gold, azathioprine and methotrexate (MTX). In general, the dose effect relation and the dose toxicity relation were disappointing, resulting in their application being restricted to late in course of the disease. At the turn of the century, treatment strategies changed. DMARD therapy was started earlier in the disease course and sometimes in combination therapy. Some Dutch clinical trials such as the COBRA, DREAM Remission Induction Study and BeSt-study showed that initiation of combination therapy including corticosteroids in an early phase of RA leads to less joint destruction and better outcomes (5-7). 10 CHAPTER 1 A major breakthrough for the treatment of RA was the development and introduction of inhibitors of Tumor Necrosis Factor (TNFi) early this century (8). If csDMARDs are unable to control RA disease activity, addition of a TNFi or other biological (b)DMARD should be considered (9). Also, ...
