Randomized multicenter trial of natalizumab in acute MS relapses: Clinical and MRI effects

P. W. O'Connor, A. Goodman, A. J. Willmer-Hulme, M. A. Libonati, L. Metz, R. S. Murray, William Sheremata, T. L. Vollmer, L. A. Stone

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Abstract

Background: Relapses in multiple sclerosis (MS) can cause significant neurologic disability. Natalizumab (Antegren) is a humanized anti-α4-integrin antibody that inhibits the trafficking of leukocytes across endothelium by blocking binding of α4β1-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.

Original languageEnglish
Pages (from-to)2038-2043
Number of pages6
JournalNeurology
Volume62
Issue number11
StatePublished - Jun 8 2004

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Multicenter Studies
Multiple Sclerosis
Recurrence
Placebos
Integrins
Vascular Cell Adhesion Molecule-1
Natalizumab
Therapeutics
Nervous System
Endothelium
Leukocytes
Antibodies

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

O'Connor, P. W., Goodman, A., Willmer-Hulme, A. J., Libonati, M. A., Metz, L., Murray, R. S., ... Stone, L. A. (2004). Randomized multicenter trial of natalizumab in acute MS relapses: Clinical and MRI effects. Neurology, 62(11), 2038-2043.

Randomized multicenter trial of natalizumab in acute MS relapses : Clinical and MRI effects. / O'Connor, P. W.; Goodman, A.; Willmer-Hulme, A. J.; Libonati, M. A.; Metz, L.; Murray, R. S.; Sheremata, William; Vollmer, T. L.; Stone, L. A.

In: Neurology, Vol. 62, No. 11, 08.06.2004, p. 2038-2043.

Research output: Contribution to journalArticle

O'Connor, PW, Goodman, A, Willmer-Hulme, AJ, Libonati, MA, Metz, L, Murray, RS, Sheremata, W, Vollmer, TL & Stone, LA 2004, 'Randomized multicenter trial of natalizumab in acute MS relapses: Clinical and MRI effects', Neurology, vol. 62, no. 11, pp. 2038-2043.
O'Connor PW, Goodman A, Willmer-Hulme AJ, Libonati MA, Metz L, Murray RS et al. Randomized multicenter trial of natalizumab in acute MS relapses: Clinical and MRI effects. Neurology. 2004 Jun 8;62(11):2038-2043.
O'Connor, P. W. ; Goodman, A. ; Willmer-Hulme, A. J. ; Libonati, M. A. ; Metz, L. ; Murray, R. S. ; Sheremata, William ; Vollmer, T. L. ; Stone, L. A. / Randomized multicenter trial of natalizumab in acute MS relapses : Clinical and MRI effects. In: Neurology. 2004 ; Vol. 62, No. 11. pp. 2038-2043.
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abstract = "Background: Relapses in multiple sclerosis (MS) can cause significant neurologic disability. Natalizumab (Antegren) is a humanized anti-α4-integrin antibody that inhibits the trafficking of leukocytes across endothelium by blocking binding of α4β1-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.",
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AU - O'Connor, P. W.

AU - Goodman, A.

AU - Willmer-Hulme, A. J.

AU - Libonati, M. A.

AU - Metz, L.

AU - Murray, R. S.

AU - Sheremata, William

AU - Vollmer, T. L.

AU - Stone, L. A.

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N2 - Background: Relapses in multiple sclerosis (MS) can cause significant neurologic disability. Natalizumab (Antegren) is a humanized anti-α4-integrin antibody that inhibits the trafficking of leukocytes across endothelium by blocking binding of α4β1-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.

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