Demyelination and inhibition of tumor necrosis factor (TNF) 

M.D. Magnano, W.H. Robinson, M.C. Genovese

ABSTRACT
The development of tumor necrosis factor alpha (TNFa) inhibitor therapy is arguably the most significant achievement in the treatment of rheumatic diseases to date. One serious potential side effect associated with these agents is the onset of neurologic signs and symptoms. In this paper we will examine the relationship of TNFa antagonism and demyelinating disease. Reviewing early laboratory and animal models, we discuss the mechanism of TNFa in central nervous system (CNS) injury and repair. Two negative studies of TNFa inhibitor therapy in the treatment of refractory multiple sclerosis (MS) are considered. 
From the manufacturers' clinical development programs and post-marketing adverse event reporting data, we report the current incidence of demyelinating symptoms associated with each of the commercially available anti-TNFa agents. Comparing these reports to the incidence of MS in society as a whole, we find the rate of new cases of neurologic disease in exposed patients is not different from the rate of expected cases. Finally we explore arguments that support and refute a potential biologic relationship between TNFa neutralization and demyelinating disease. 

Key words:
Cytokines, tumor necrosis factor, rheumatoid arthritis, multiple sclerosis, treatment, side effects, demyelination.

Please address correspondence to: Mark C. Genovese, MD, 1000 Welch Road #203, Palo Alto, California 94304, USA. 
E-mail: genovese@stanford.edu

Clin Exp Rheumatol 2004; 22 (Suppl. 35): S134-S140.
© Copyright Clinical and Experimental Rheumatology 2004.