Biological agents: a novel approach to the therapy of rheumatoid arthritis

Rheumatoid arthritis (RA) is the most common chronic autoimmunopathy, clinically leading to joint destruction as a consequence of the chronic inflammatory processes. The pathogenesis of this disabling disease is not well understood, but molecular events leading to tissue inflammation with cartilage and bone destruction are now defined in more detail. Established therapy, slow acting disease-modifying antirheumatic drugs (DMARDs) as with low-dose methotrexate (MTX) are the accepted 'golden standard' therapies and both lead to a significant improvement of disease symptoms, however are unable to stop joint destruction. Due to these disappointing treatment options and the identification of some inflammatory mediators as therapeutic targets, novel therapeutic agents such as monoclonal antibodies (mAbs), cytokine receptor-human immunoglobulin constructs or recombinant human proteins have been tested in RA with some success. In particular, clinical trials testing anti-TNF-alpha agents either alone or in combination with MTX have convincingly demonstrated the feasibility and efficacy of these novel approaches to the therapy of RA. Importantly, a clinical trial testing combination therapy with chimeric (mouse-human) anti-TNF-alpha mAb cA2 (Remicadetrade mark) and MTX could, for the first time in any RA trial, show that average radiological progression in the cA2/MTX groups could be completely prevented over a 12 month observation period. Similar encouraging results might evoke from trials employing other TNF-alpha-directed agents like the fully human mAb D(2)E7 or the p75 TNF-alpha-receptor-Ig construct, etanercept.