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
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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.
KeywordsBlack holes Glatiramer acetate GALA study Magnetic resonance imaging Relapsing–remitting MS T1-hypointense lesions
We thank the patients and site personnel involved with this study and Peter Feldman, PhD (Teva Pharmaceuticals), and Lisa Grauer, MSc (Chameleon Communications International with funding and writing/editorial support from Teva Pharmaceutical Industries), for editorial assistance in the preparation of this report. This study was funded by Teva Pharmaceutical Industries Ltd, Petach Tikva, Israel.
Conflicts of interest
R. Zivadinov: personal compensation from Teva, Biogen Idec, EMD Serono, Genzyme-Sanofi, Claret Medical, Novartis for speaking and consultant fees; financial support for research activities from Biogen Idec, Teva, Novartis, Genzyme-Sanofi, Claret Medical, Greatbatch.
M. Dwyer: consulting fees from Claret Medical, EMD Serono.
J. Steinerman, V. Knappertz, H. Barkay: employees of Teva Pharmaceutical Industries.
O. Khan: research funding from NIH, NINDS, NMSS, Teva, Biogen Idec, Genzyme, Roche, Novartis; consulting fees from Biogen Idec, Genzyme, Novartis; speaker bureaus for Teva, Novartis, Biogen Idec.
All institutional review boards or ethics committees of the particpating centers approved the protocol and all patients gave written, informed consent before any study-related procedures were performed.