title: Effect of glatiramer acetate three-times weekly on the evolution of new, active multiple sclerosis lesions into T1-hypointense "black holes": a post hoc magnetic resonance imaging analysis.
abstract: Conversion of active lesions to black holes has been associated with disability progression in subjects with relapsing-remitting multiple sclerosis (RRMS) and represents a complementary approach to evaluating clinical efficacy. The objective of this study was to assess the conversion of new active magnetic resonance imaging (MRI) lesions, identified 6 months after initiating treatment with glatiramer acetate 40 mg/mL three-times weekly (GA40) or placebo, to T1-hypointense black holes in subjects with RRMS. Subjects received GA40 (n = 943) or placebo (n = 461) for 12 months. MRI was obtained at baseline and Months 6 and 12. New lesions were defined as either gadolinium-enhancing T1 or new T2 lesions at Month 6 that were not present at baseline. The adjusted mean numbers of new active lesions at Month 6 converting to black holes at Month 12 were analyzed using a negative binomial model; adjusted proportions of new active lesions at Month 6 converting to black holes at Month 12 were analyzed using a logistic regression model. Of 1,292 subjects with complete MRI data, 433 (50.3 %) GA-treated and 247 (57.2 %) placebo-treated subjects developed new lesions at Month 6. Compared with placebo, GA40 significantly reduced the mean number (0.31 versus 0.45; P = .0258) and proportion (15.8 versus 19.6 %; P = .006) of new lesions converting to black holes. GA significantly reduced conversion of new active lesions to black holes, highlighting the ability of GA40 to prevent tissue damage in RRMS.
authors.affiliation: Department of Neurology, Buffalo Neuroimaging Analysis Center, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, 100 High St., Buffalo, NY, 14203, USA, rzivadinov@bnac.net.
authors.forename: Robert
authors.initials: R
authors.lastname: Zivadinov
authors.forename: Michael
authors.initials: M
authors.lastname: Dwyer
authors.forename: Hadas
authors.initials: H
authors.lastname: Barkay
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Steinerman
authors.forename: Volker
authors.initials: V
authors.lastname: Knappertz
authors.forename: Omar
authors.initials: O
authors.lastname: Khan
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D000068717:Glatiramer Acetate / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007391:International Cooperation; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D007166:Immunosuppressive Agents; D000068717:Glatiramer Acetate