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From the Department of Neurology (Drs. van Oosten and Polman), Free University Hospital, Amsterdam, the Netherlands; the National Hospital, Institute of Neurology (Drs. Lai, Miller, Moseley, Thompson, and Rudge), Queen Square, London, United Kingdom; the Department of Neurology (Drs. Hodgkinson, McLeod, and McDougall), Liverpool Hospital, University of New South Wales, Liverpool, Australia; the Department of Diagnostic Radiology (Dr. Barkhof), Free University Hospital, Amsterdam, the Netherlands; and the Department of Epidemiology and Biostatistics (Dr. Adèr), Faculty of Medicine, Free University, Amsterdam, the Netherlands.
Address correspondence and reprint requests to Dr Polman, Professor of Neurology, Department of Neurology, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands.
We report the results of a randomized, double-blind, placebo-controlled exploratory trial of the chimeric monoclonal anti-CD4 antibody cM-T412 in 71 patients suffering from active relapsing-remitting and secondary progressive multiple sclerosis. Infusion of the antibody produced frequent but usually minor side effects and resulted in a long-lasting reduction of circulating CD4-positive T cells. There was no significant effect on the primary measure of efficacy, the number of active lesions on monthly gadolinium-enhanced MRI over 9 months. Further statistical evaluation provided evidence that the degree of depletion of CD4-positive cells was important with regard to treatment efficacy; using CD4 counts as a covariate there was a statistically significant effect on the number of active lesions over 18 months (p= 0.04). There was a statistically significant reduction of 41% in the number of clinical relapses (a secondary efficacy parameter) after 9 months(p = 0.02), which was still present after 18 months, but this finding may be partly due to physician unblinding. Other secondary efficacy parameters (Expanded Disability Status Scale progression, number of courses of methylprednisolone) were not influenced by anti-CD4 treatment. We conclude that intravenous treatment with the monoclonal antibody cM-T412 in the dosage we used results in a substantial and sustained reduction of the number of circulating CD4-positive cells, but is not able to reduce MS activity as measured by monthly gadolinium-enhanced MRI, and is therefore unlikely to have a beneficial effect on the clinical disease course. We found preliminary evidence suggesting that more aggressive depletion of CD4-positive cells might lead to a more substantial reduction in MRI activity.
Supported by the "Stichting Vrienden MS Research," The Hague, the Netherlands.
Received June 3, 1996. Accepted in final form April 25, 1997.
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