Anti-TNF Therapy of RA: What Can We Learn about Chronic Disease?

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Anti- TNF Therapy of Rheumatoid Arthritis: What Can We Learn about

Chronic Disease?

Chapter Authors: Marc Feldmann, Fionula M. Brennan, Ewa Paleolog,

Cope, , , Jim Woody, Ravinder N.

Maini

Series: Novartis Foundation Symposia

Summary

The importance of tumour necrosis factor (TNF) in rheumatoid

arthritis (RA) was initially proposed on the basis of analysis of

cytokine gene regulation at the local site of the disease, the

synovium. This was then verified in animal models and established in

an extensive series of clinical trials, culminating in now 250 000

treated patients with either of two approved TNF inhibitors,

antibody or fusion protein. The degree and magnitude of clinical

benefit has enabled analyses of the mechanism by which anti-TNF

benefits, and hence insights into important steps in the disease

process. It was found that essentially all aspects of RA were

ameliorated, and important mechanisms of benefit involved diminution

of multiple pro-inflammatory cytokines, adhesion molecules and

chemokines, leading to reduced cell trafficking, reduced

angiogenesis and most importantly halting of joint destruction. What

of the problems? Safety is better than prior drugs, but there is a

small increase in severe infections, smaller than might have been

anticipated. Cost is the major drawback limiting greater use. In

view of the central pathological processes down-regulated, and their

role in many diseases, the early clinical success of anti-TNF in RA

led to subsequent successful trials and registration in Crohn's

disease and juvenile rheumatoid arthritis, and successful trials in

ankylosing spondylitis, psoriasis and psoriatic arthritis. The era

of anti-cytokine therapeutics is just dawning.

http://www3.interscience.wiley.com/cgi-bin/summary/109088430/SUMMARY