Drugs

, Volume 55, Issue 5, pp 613–620

The Future Role of Anti-Tumour Necrosis Factor (TNF) Products in the Treatment of Rheumatoid Arthritis

Authors

  • Giovanni Camussi
    • Nephrology and Clinical Immunology, Department of Clinical and Biological SciencesUniversity of Pavia
  • Enrico Lupia
    • Nephrology and Clinical Immunology, Department of Clinical and Biological SciencesUniversity of Pavia
Leading Article

DOI: 10.2165/00003495-199855050-00001

Cite this article as:
Camussi, G. & Lupia, E. Drugs (1998) 55: 613. doi:10.2165/00003495-199855050-00001

Summary

Tumour necrosis factor-α (TNFα) is a pleiotropic cytokine which is overproduced in rheumatoid joints primarily by macrophages. This cytokine has a potentialpathogenic role in the establishment of rheumatoid synovitis, in the formationof pannus tissue and in the process of joint destruction, as it increases synoviocyte proliferation and triggers a cascade of secondary mediators involved in the recruitment of inflammatory cells, in neo-angiogenesis and in the process of joint destruction. These findings made TNFα a potential target for anticytokine therapy.Experimental studies have shown that TNFα blockade by monoclonal antibodies or by soluble TNF receptor reduced the extent and severity of arthritis bothin collagen-induced arthritis in mice and in transgenic mice overexpressingTNFα, which develop a rheumatoid-like destructive arthritis. Clinical studiesbased on the use of anti-TNFα antibodies or soluble receptors have suggested a potential beneficial effect of TNFα-blocking therapy in inducing amelioration of inflammatory parameters in patients with long-standing active disease. In these patients anti-TNFα therapy induces a rapid improvement in multiple clinical assessment of disease activity, including morning stiffness, pain score, Ritchie articular index and swollen joint count. The clinical benefits are associated withan improvement in some serological parameters, such as C-reactive protein and serum amyloid-A, erythrocyte sedimentation rate, blood cytokine levels, haemoglobin, white cells and platelet counts, rheumatoid factor titre and histological features of the synovium. However, it remains to be determined whether anti-TNFα therapy may be useful in the long term management of rheumatoid patients and in the achievement of better outcomes of disease. Because TNFα production also serves a specific function in host defence against infections and tumours, the adverse effects of long term anti-TNFα therapy must be carefully evaluated. In addition, targeting a single mediator may be not sufficient to block the complex inflammatory response in rheumatoid arthritis. For these reasons therapeutic strategies aimed at concomitantly interfering with multiple pathogenic pathways are currently under investigation.

Copyright information

© Adis International Limited 1998