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Randomized multicenter trial of natalizumab in acute MS relapses

Clinical and MRI effects

From St. Michael’s Hospital (Dr. O’Connor), Toronto, Ontario, and Clinical Neurosciences (Dr. Metz), Foothills Hospital, Calgary, Alberta, Canada; and Department of Neurology (Dr. Goodman), University of Rochester Medical Center, NY, Elan Pharmaceuticals, Inc. (Dr. Willmer-Hulme, M.A. Libonati), San Diego, CA, Rocky Mountain MS Center (Dr. Murray), Englewood, CO, Department of Neurology (Dr. Sheremata), University of Miami School of Medicine, FL, Division of Neurology (Dr. Vollmer), Barrow Neurological Institute, Phoenix, AZ, and Mellen Center for MS Research and Treatment (Dr. Stone), Department of Neurology, Cleveland Clinic Foundation, OH.

Address correspondence and reprint requests to Dr. P.W. O’Connor, St. Michael’s Hospital, 30 Bond St., Suite 3-007 Shuter Wing, Toronto, Ontario, Canada M5B 1W8; e-mail: oconnorp{at}smh.toronto.on.ca

Background: Relapses in multiple sclerosis (MS) can cause significant neurologic disability. Natalizumab (Antegren) is a humanized anti-4-integrin antibody that inhibits the trafficking of leukocytes across endothelium by blocking binding of 4ß1-integrin to vascular cell adhesion molecule-1.

Objective: To assess the effects of a single dose of IV natalizumab administered soon after the onset of MS relapses.

Methods: In this randomized, double-blind, multicenter trial, the effects of a single dose of IV natalizumab administered soon after the onset of MS relapses were assessed. MS patients (n = 180) in acute relapse were randomly assigned to receive a single dose of natalizumab 1 or 3 mg/kg or placebo and were followed for 14 weeks.

Results: There was no difference in Expanded Disability Status Scale (EDSS) score change over time between treatment and placebo groups. In all three groups, approximately half of patients showed EDSS improvement after 2 weeks, rising to 67% by 8 weeks. EDSS improved by a mean value of 0.8 point at week 1, 1.2 points at week 4, and 1.6 points at week 8 in the natalizumab group compared with EDSS improvement of 1.0 point at week 1, 1.6 points at week 4, and 1.6 points at week 8 in the placebo group. A significant decrease in Gd-enhancing lesion volume was seen in both active treatment groups at weeks 1 and 3 compared with placebo.

Conclusions: A single dose of IV natalizumab did not hasten clinical recovery after relapse, although a significant decrease in Gd-enhancing lesion volume was observed at 1 and 3 weeks after treatment. These MRI findings are consistent with prior studies of natalizumab and support its further investigation as an agent for the treatment of MS.

Received June 25, 2003. Accepted in final form February 3, 2004.

*See the Appendix on page 2043 for a list of Group members.

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