The effect of anti-alpha 4 integrin antibody on brain lesion activity in MS

Objective: To determine the effect of humanized monoclonal antibody against alpha 4 integrin (reactive with alpha 4 beta 1 integrin or very-late antig en-4) on MRI lesion activity in MS. Methods: A randomized, double-blind, pl acebo-controlled trial in 72 patients with active relapsing-remitting and s econdary progressive MS was performed. Each patient received two IV infusio ns of anti-4 alpha integrin antibody (natalizumab; Antegren) or placebo 4 w eeks apart and was followed up for 24 weeks with serial MRI and clinical as sessment. Results: The treated group exhibited significantly fewer new acti ve lesions (mean 1.8 versus 3.6 per patient) and new enhancing lesions (mea n 1.6 versus 3.3 per patient) than the placebo group over the first 12 week s. There was no significant difference in the number of new active or new e nhancing lesions in the second 12 weeks of the study. The number of baselin e-enhancing lesions (i.e., lesions that enhanced on the baseline scan) that continued to enhance 4 weeks following the first treatment was not signifi cantly different between the two groups. The number of patients with acute MS exacerbations was not significantly different in the two groups during t he first 12 weeks (9 in the treated group versus 10 in placebo) but was hig her 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: Shor t-term treatment with monoclonal antibody against alpha 4 integrin results in a significant reduction in the number of new active lesions on MRI. Furt her studies will be required to determine the longer term effect of this tr eatment on MRI and clinical outcomes.