[Value of anti-TNF-alpha molecules in inflammatory and infectious diseases].

INTRODUCTION

The pathophysiological interest of tumor necrosis factor-alpha (TNF-alpha) has been recently reported in inflammatory and infectious diseases. Thus, TNF-alpha blockade has become a new field of therapeutical research.

CURRENT KNOWLEDGE AND KEY POINTS

Several biological agents specifically directed against TNF-alpha are available: anti-TNF-alpha monoclonal antibodies on the one hand--either mainly murine sequence (cA2), partially humanized (CDP 571) or fully human (D2E7)--and TNF-alpha soluble receptors on the other hand (lenercept or etanercept). The first clinical studies reveal interesting results. In rheumatoid arthritis (cA2, etanercept), these molecules may be used either alone or in synergistic combination with methotrexate. They produce a significant response compared to placebo or methotrexate alone, without loss of efficacy in medium-term treatment. In Crohn's disease (cA2 CDP571), they reduce significantly the activity of the disease, compared to placebo, and cA2 makes it possible to accelerate closure of the fistulas. The studies of severe sepsis did not reveal a significant efficacy, however, and only one study has been published on malignant disease, with a possible interesting effect. Even if these medications are usually well tolerated, the frequency of infections is slightly increased. The development of anti-DNA antibodies has also been reported, but drug-induced lupus is highly unusual.

FUTURE PROSPECTS AND PROJECTS

Further studies will define the place of anti-TNF-alpha biological agents among the other available treatments of rheumatoid arthritis and Crohn's disease. Because of their high cost, these drugs will probably be limited to patients with active inflammatory disease despite more conventional treatments.