Biological agents for rheumatoid arthritis: targeting both physical function and structural damage

Rheumatoid arthritis (RA) is a chronic progressive inflammatory disease of multifactorial aetiology. The pivotal role of proinflammatory cytokines in the pathogenesis and perpetuation of synovitis has been demonstrated in basic research since the late 1980s and in clinical research since the early 1990s. Biological agents are monoclonal antibodies or recombinant forms of natural inhibitory molecules which selectively interact with molecules or cell receptors affecting immune or inflammatory processes. In RA, etanercept, infliximab and adalimumab are currently available to target tumour necrosis factor (TNF) and an interleukin (IL)-1 receptor antagonist is available to target IL-1 activity. Trials have shown benefits as monotherapy, although the best results for disease control are seen when biological agents are coadministered with methotrexate. The use of these agents in clinical trials and in practice has resulted in dramatic improvements in RA disease control, and delay and prevention of radiographic damage. The remarkable benefits to patients in well-being, quality of life and function, and the speed of onset of action are reminiscent of the early days of corticosteroid use. Ten years after the first clinical trials of anti-TNF therapies, the adverse effect profile is evolving and includes, for anti-TNF therapy, an increased risk of infections associated with immune suppression, injection and infusion reactions, and a risk of drug induced autoimmune syndromes such as systemic lupus erythematosus. Where these drugs are affordable, the prognosis of individuals for control of severe RA is better than ever before. This manuscript summarises the clinical trial results and post-marketing information regarding the biological agents currently in use for RA.