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	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by von Andrian, U. H. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background In patients with multiple sclerosis, inflammatory brain lesions 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. Natalizumab is an ₄ integrin antagonist that reduced the development of brain lesions in experimental models and in a preliminary study of patients with multiple sclerosis.

Methods In a randomized, double-blind trial, we randomly assigned a total of 213 patients with relapsing–remitting or relapsing secondary progressive multiple sclerosis to receive 3 mg of intravenous natalizumab per kilogram of body weight (68 patients), 6 mg per kilogram (74 patients), or placebo (71 patients) every 28 days for 6 months. The primary end point was the 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.

Results There were marked reductions in the mean number of new lesions in both natalizumab groups: 9.6 per patient in the placebo group, as compared with 0.7 in the group given 3 mg of natalizumab per kilogram (P<0.001) and 1.1 in the group given 6 mg of natalizumab per kilogram (P<0.001). Twenty-seven patients in the placebo group had relapses, as compared with 13 in the group given 3 mg of natalizumab per kilogram (P=0.02) and 14 in the group given 6 mg of natalizumab per kilogram (P=0.02). The placebo group reported a slight worsening in well-being (a mean decrease of 1.38 mm on a 100-mm visual-analogue scale), whereas the natalizumab groups reported an improvement (mean increase of 9.49 mm in the group given 3 mg of natalizumab per kilogram and 6.21 mm in the group given 6 mg of natalizumab per kilogram).

Conclusions In a placebo-controlled trial, treatment with natalizumab led to fewer inflammatory brain lesions and fewer relapses over a six-month period in patients with relapsing multiple sclerosis.

Source Information

From the Institute of Neurology, London (D.H.M., C.M.D., K.A.M.); Wayne State University School of Medicine, Detroit (O.A.K.); the University of Miami School of Medicine, Miami (W.A.S.); University Hospital, Nottingham, United Kingdom (L.D.B.); the London Multiple Sclerosis Clinic, London, Ont., Canada (G.P.A.R.); Elan Pharmaceuticals, San Francisco (M.A.L., A.J.W.-H.); and St. Michael's Hospital, University of Toronto, Toronto (P.W.O.).

Address reprint requests to Dr. Miller at the Department of Neuroinflammation, Institute of Neurology, Queen Sq., London WC1N 3BG, United Kingdom, or at d.miller{at}ion.ucl.ac.uk.

Full Text of this Article

Related Letters:

Natalizumab for Relapsing Multiple Sclerosis
Chaudhuri A., Behan P. O., Miller D. H., O'Connor P. W.
Extract | Full Text | PDF  
N Engl J Med 2003; 348:1598-1599, Apr 17, 2003. Correspondence

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