title: Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Glatiramer acetate, approved for the treatment of relapsing-remitting multiple sclerosis, reduces relapses and disease activity and burden monitored by MRI. We assessed the efficacy of early treatment with glatiramer acetate in delaying onset of clinically definite multiple sclerosis.
  
  
  METHODS
  In this randomised, double-blind trial, undertaken in 80 sites in 16 countries, 481 patients presenting with a clinically isolated syndrome with unifocal manifestation, and two or more T2-weighted brain lesions measuring 6 mm or more, were randomly assigned to receive either subcutaneous glatiramer acetate 20 mg per day (n=243) or placebo (n=238) for up to 36 months, unless they converted to clinically definite multiple sclerosis. The randomisation scheme used SAS-based blocks stratified by centre, and patients and all personnel were masked to treatment assignment. The primary endpoint was time to clinically definite multiple sclerosis, based on a second clinical attack. Analysis was by intention to treat. A preplanned interim analysis was done for data accumulated from 81% of the 3-year study exposure. This study was registered with ClinicalTrials.gov, number NCT00666224.
  
  
  RESULTS
  All randomly assigned participants were analysed for the primary outcome. Glatiramer acetate reduced the risk of developing clinically definite multiple sclerosis by 45% compared with placebo (hazard ratio 0.55, 95% CI 0.40-0.77; p=0.0005). The time for 25% of patients to convert to clinically definite disease was prolonged by 115%, from 336 days for placebo to 722 days for glatiramer acetate. The most common adverse events in the glatiramer acetate group were injection-site reactions (135 [56%] glatiramer acetate vs 56 [24%] placebo) and immediate post-injection reactions (47 [19%] vs 12 [5%]).
  
  
  CONCLUSIONS
  Early treatment with glatiramer acetate is efficacious in delaying conversion to clinically definite multiple sclerosis in patients presenting with clinically isolated syndrome and brain lesions detected by MRI.
  
  
  BACKGROUND
  Teva Pharmaceutical Industries, Israel.
authors.affiliation: Institute of Experimental Neurology, Department of Neurology, University Vita-Salute, Scientific Institute San Raffaele, Milan, Italy. g.comi@hsr.it
authors.forename: G
authors.initials: G
authors.lastname: Comi
authors.forename: V
authors.initials: V
authors.lastname: Martinelli
authors.forename: M
authors.initials: M
authors.lastname: Rodegher
authors.forename: L
authors.initials: L
authors.lastname: Moiola
authors.forename: O
authors.initials: O
authors.lastname: Bajenaru
authors.forename: A
authors.initials: A
authors.lastname: Carra
authors.forename: I
authors.initials: I
authors.lastname: Elovaara
authors.forename: F
authors.initials: F
authors.lastname: Fazekas
authors.forename: H P
authors.initials: HP
authors.lastname: Hartung
authors.forename: J
authors.initials: J
authors.lastname: Hillert
authors.forename: J
authors.initials: J
authors.lastname: King
authors.forename: S
authors.initials: S
authors.lastname: Komoly
authors.forename: C
authors.initials: C
authors.lastname: Lubetzki
authors.forename: X
authors.initials: X
authors.lastname: Montalban
authors.forename: K M
authors.initials: KM
authors.lastname: Myhr
authors.forename: M
authors.initials: M
authors.lastname: Ravnborg
authors.forename: P
authors.initials: P
authors.lastname: Rieckmann
authors.forename: D
authors.initials: D
authors.lastname: Wynn
authors.forename: C
authors.initials: C
authors.lastname: Young
authors.forename: M
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy*; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D055502:Secondary Prevention; D013577:Syndrome; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate