title: Randomized multicenter trial of natalizumab in acute MS relapses: clinical and MRI effects.
abstract: BACKGROUND
  Relapses in multiple sclerosis (MS) can cause significant neurologic disability. Natalizumab (Antegren) is a humanized anti-alpha4-integrin antibody that inhibits the trafficking of leukocytes across endothelium by blocking binding of alpha4beta1-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.
authors.affiliation: St. Michael's Hospital, Toronto, Ontario, Canada. oconnorp@smh.toronto.on.ca
authors.forename: P W
authors.initials: PW
authors.lastname: O'Connor
authors.forename: A
authors.initials: A
authors.lastname: Goodman
authors.forename: A J
authors.initials: AJ
authors.lastname: Willmer-Hulme
authors.forename: M A
authors.initials: MA
authors.lastname: Libonati
authors.forename: L
authors.initials: L
authors.lastname: Metz
authors.forename: R S
authors.initials: RS
authors.lastname: Murray
authors.forename: W A
authors.initials: WA
authors.lastname: Sheremata
authors.forename: T L
authors.initials: TL
authors.lastname: Vollmer
authors.forename: L A
authors.initials: LA
authors.lastname: Stone
mesh_terms: D000208:Acute Disease; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003287:Contrast Media; D004311:Double-Blind Method; D005260:Female; D005682:Gadolinium; D006801:Humans; D039441:Integrin alpha4 / Q000276:immunology; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology; D000069442:Natalizumab; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003287:Contrast Media; D000069442:Natalizumab; D039441:Integrin alpha4; D005682:Gadolinium