Ann Rheum Dis 61:ii70-ii73 doi:10.1136/ard.61.suppl_2.ii70
  • Clinical and radiological aspects of biologics

Adalimumab (a fully human anti-tumour necrosis factor α monoclonal antibody) in the treatment of active rheumatoid arthritis: the initial results of five trials

  1. R Rau
  1. Department of Rheumatology, Evangelisches Fachkrankenhaus Ratingen, Ratingen, Germany
  1. Correspondence to:
    Dr R Rau, Rheumaklinik, Evangelisches Fachkrankenhaus, Rosenstr 2 D-40882 Ratingen, Germany;

    Rheumatoid arthritis (RA), a common, chronic, idiopathic autoimmune disease, is characterised by symmetrical synovitis, inflammatory exudates in the joint cavity, and erosion of articular cartilage and marginal bone.1 Standard treatment for RA typically consists of traditional disease modifying antirheumatic drugs (DMARDs), corticosteroids, non-steroidal anti-inflammatory drugs, and analgesics.2 Despite these various treatments, many patients with RA continue to experience substantial disease activity, with progressive joint damage and accompanying functional loss. In recent years, insights into the pathophysiology of RA have lead to the development of novel therapeutic strategies that target underlying disease processes, the most promising of which entails neutralisation of tumour necrosis factor α (TNFα).3


    TNFα is a potent proinflammatory cytokine that plays a critical part in the progression of inflammatory synovitis and articular matrix degradation in RA.3 Increased concentrations of TNFα are found in the synovial fluid and serum of patients with active RA.4 Derived primarily from activated monocytes and macrophages, TNFα promotes the synthesis of other proinflammatory cytokines; stimulates endothelial cells to express adhesion molecules that attract leucocytes into affected joints; accelerates the production of metalloproteinases by synovial macrophages, fibroblasts, osteoclasts, and chondrocytes; and suppresses the synthesis of cartilage proteoglycans.3,5,6 Because of these multiple actions, TNFα may have a more dominant function in the pathogenesis of RA than other proinflammatory cytokines such as interleukin 1.3 The effects of TNFα are triggered by its binding to two different membrane receptors (p55 and p75) that are expressed by certain cell types, including neutrophils, vascular endothelial cells, and fibroblasts.

    Over the past two decades, investigators have not only delineated the spectrum of pathological actions of TNFα but also devised ways of effectively blocking this cytokine, offering renewed hope to patients with refractory, moderate to severe RA.3 Currently, two biologically based DMARDs …