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4 integrin antibody on brain lesion activity in MS
From the Institute of Neurology (Drs. Tubridy, Moseley, and Miller, and D.G. MacManus), Queen Square, London; Southern General Hospital (Drs. Behan and Chaudhuri), Glasgow; Orsett Hospital (Dr. Capildeo), Essex; North Staffordshire Royal Infirmary (Dr. Hawkins), Stoke-on-Trent; Guy’s Hospital (Drs. Hughes and Sharrack), London; Radcliffe Infirmary (Dr. Palace), Oxford; Dundee Royal Infirmary (Drs. Forbes and Swingler), Dundee; The Walton Centre for Neurology & Neurosurgery (Dr. Young), Liverpool; and Elan Pharma Limited (Dr. Donoghue), Letchworth, UK.
Address correspondence and reprint requests to Dr. D.H. Miller, Professor of Neurology, NMR Unit, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
OBJECTIVE: To determine the effect of humanized monoclonal antibody against 
4 integrin (reactive with 4ß1 integrin or very-late antigen–4) on MRI lesion activity in MS.
METHODS: A randomized, double-blind, placebo-controlled trial in 72 patients with active relapsing-remitting and secondary progressive MS was performed. Each patient received two IV infusions of anti-4 integrin antibody (natalizumab; Antegren) or placebo 4 weeks apart and was followed up for 24 weeks with serial MRI and clinical assessment.
RESULTS: The treated group exhibited significantly fewer new active lesions (mean 1.8 versus 3.6 per patient) and new enhancing lesions (mean 1.6 versus 3.3 per patient) than the placebo group over the first 12 weeks. There was no significant difference in the number of new active or new enhancing lesions in the second 12 weeks of the study. The number of baseline-enhancing lesions (i.e., lesions that enhanced on the baseline scan) that continued to enhance 4 weeks following the first treatment was not significantly different between the two groups. The number of patients with acute MS exacerbations was not significantly different in the two groups during the first 12 weeks (9 in the treated group versus 10 in placebo) but was higher in the treatment group in the second 12 weeks (14 versus 3; p = 0.005). The study was not, however, designed to look definitively at the effect of treatment on relapse rate. Treatment was well tolerated.
CONCLUSIONS: Short-term treatment with monoclonal antibody against 4 integrin results in a significant reduction in the number of new active lesions on MRI. Further studies will be required to determine the longer term effect of this treatment on MRI and clinical outcomes.
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