By Anne MacLennan
New England Journal of Medicine (NEJM)
Treatment with natalizumab reduces inflammatory brain lesions and relapses over six months in patients with relapsing multiple sclerosis.
This is the main finding of a multicentre placebo controlled study led by Dr. David H. Miller from the Institute of Neurology, in London, and the International Natalizumab Multiple Sclerosis Trial Group.
Inflammatory brain lesions in these patients appear to arise from autoimmune responses involving activated lymphocytes and monocytes.
The glycoprotein 4 integrin is expressed on the surface of these cells and plays a critical part in their adhesion to the vascular endothelium and migration into the parenchyma.
The study drug, a 4 integrin antagonist, has already been found to reduce development of brain lesions in experimental models and also in a preliminary study of multiple sclerosis patients.
Participants in this randomised, double blind trial were 213 patients with relapsing-remitting or relapsing secondary progression multiple sclerosis. Of these, 68 received 3 mg/kg of intravenous natalizumab, 74 received 6 mg/kg and 71 received placebo every 28 days for six months.
Primary end point was number of new brain lesions on monthly gadolinium-enhanced magnetic resonance imaging during the six-month treatment period. Clinical outcomes included relapses and self-reported well-being.
Marked reductions were seen in the mean number of new lesions in both natalizumab groups -- 9.6 per patient in the placebo group versus 0.7 in the group on natalizumab 3 mg (p<0.001) and 1.1 in the group on six 6 mg (p<0.001). Moreover, 27 patients on placebo had relapses as compared with 13 in the group on 3 mg natalizumab (p=0.02) and 14 in the group on 6 mg (p=0.02).
Natalizumab treatment therefore led to fewer inflammatory brain lesions and fewer relapses over a six-month period in relapsing multiple sclerosis patients, these authors conclude.
N Engl J Med 2002;348:15-23.
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