title: The Effect of Three Times a Week Glatiramer Acetate on Cerebral T1 Hypointense Lesions in Relapsing-Remitting Multiple Sclerosis.
abstract: OBJECTIVE
  Two definitions of T1 hypointense (T1H) lesions can be derived from pre-contrast images: those that may or may not have a corresponding gadolinium-enhancing correlate on post-contrast images (T1H total), and those that are simultaneously non-gadolinium-enhancing on post-contrast scans (T1H non-enhancing). To determine the differences in lesion evolution between these two T1H definitions, we examined the effect of glatiramer acetate 40 mg/mL three times weekly subcutaneous injection (GA40) on the number of new or enlarging T1H total and T1H non-enhancing lesions in patients with relapsing-remitting multiple sclerosis (RRMS).
  
  
  METHODS
  The Phase III GALA study randomized 1404 RRMS subjects 2:1 to receive GA40 or placebo for 12 months. MRI scans were obtained at baseline and at months 6 and 12. Cumulative numbers of T1H total and of T1H non-enhancing lesions were analyzed using an adjusted negative binomial regression model. A total of 1,357 patients had MRI data collected at either the month 6 or month 12 visit.
  
  
  RESULTS
  Among the 1,357 patients with MRI scans performed at either the month 6 or month 12 visit, 883 treated with GA40 developed an adjusted cumulative mean of 1.72 T1H total lesions versus 2.62 in 440 placebo controls (risk ratio, .66; 95% CI, .54-.80; P < .0001). On T1H non-enhanced scans, GA40-treated patients developed an adjusted cumulative mean of 1.35 T1H non-enhancing lesions versus 1.91 in placebo controls (risk ratio, .71; CI, .58-.87; P = .0009).
  
  
  CONCLUSIONS
  GA40 significantly reduced the number of new or enlarging T1H total lesions and T1H non-enhancing lesions compared with placebo. Although the treatment effect magnitude was comparable with both definitions, the use of T1H non-enhancing lesions may be more relevant for more uniform standardization in future clinical trials.
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY.
authors.forename: Robert
authors.initials: R
authors.lastname: Zivadinov
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Dwyer
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY.
authors.forename: Deepa P
authors.initials: DP
authors.lastname: Ramasamy
authors.affiliation: Teva Pharmaceutical Industries, Frazer, PA.
authors.forename: Mat D
authors.initials: MD
authors.lastname: Davis
authors.affiliation: Teva Pharmaceutical Industries, Frazer, PA.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Steinerman
authors.affiliation: The Sastry Foundation Advanced Imaging Laboratory & Multiple Sclerosis Center, Department of Neurology, Wayne State University School of Medicine, Detroit, MI.
authors.forename: Omar
authors.initials: O
authors.lastname: Khan
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects*; D004334:Drug Administration Schedule; D005260:Female; D005682:Gadolinium; D000068717:Glatiramer Acetate / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D000068717:Glatiramer Acetate; D005682:Gadolinium
keywords: Glatiramer acetate; T1 hypointense lesions; gadolinium-enhancing lesions; relapsing-remitting multiple sclerosis