Promising Novel Therapy for Multiple Sclerosis
Promising Novel Therapy for Multiple Sclerosis
Abstract & Commentary
Source: Miller DH, et al. A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2003;348:15-23.
Natalizumab (Antegren) is a humanized monoclonal antibody against an alpha-4 integrin expressed on activated lymphocytes, which is required for adhesion to the vascular endothelium and penetration into the nervous system. In this randomized, double-blind trial, a total of 213 patients with relapsing-remitting or relapsing secondary progressive multiple sclerosis were assigned to 1 of 3 groups: natalizumab at 3 or 6 mg/kg (68 and 74 patients, respectively), or placebo (71 patients), by infusion every month for 6 months. The primary end point was the number of new gad-enhancing brain lesions on monthly MRIs. Clinical outcomes of relapse rate and self-reported well-being were also measured. There were marked reductions in the mean number of gad-enhancing lesions in both treated groups: 0.7 and 1.1 new lesions in the 3 and 6 mg/kg groups, respectively, compared with 9.6 lesions in the placebo group (P < .001). There were corresponding reductions in clinical relapses: 13 and 14 attacks in the 3 and 6 mg/kg groups, compared with 27 attacks in the placebo group (P = .02). The patients also subjectively felt better in the treated groups.
Commentary
An early step in the destructive inflammatory pathology in multiple sclerosis is the attachment of activated lymphocytes and monocytes to the vascular endothelium and subsequent entry into the brain parenchyma. Hence, the selective blockade of adhesion molecules by monoclonal antibody technology, to limit cell penetration into the central nervous system, would appear to be a logical therapeutic strategy. The above study demonstrates by convincing MRI and clinical measures the ability of natalizumab to significantly reduce disease activity in multiple sclerosis. These findings will need to be confirmed in larger trials of longer duration, which are currently under way. — Brian R. Apatoff
Dr. Apatoff is Assistant Editor of Neurology Alert and Associate Professor of Neurology, New York Presbyterian Hospital—Cornell Campus.
In this randomized, double-blind trial, a total of 213 patients with relapsing-remitting or relapsing secondary progressive multiple sclerosis were assigned to 1 of 3 groups: natalizumab at 3 or 6 mg/kg (68 and 74 patients, respectively), or placebo (71 patients), by infusion every month for 6 months.
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