Effect of Interferon Beta-1B and Glatiramer Acetate on New MTR Brain Lesions in MS (P07.104)

OBJECTIVE: To determine the relative treatment effect of glatiramer acetate (GA) and interferon beta-1b (IFN) on the evolution of new magnetization transfer ratio (MTR) lesions.BACKGROUND: Analysis of the evolution of black holes in the BECOME study, a head to head trial of GA and IFN in which subjects randomized to either treatment underwent monthly MRI for 12 to 24 months, has been reported. Here we used MTR to identify new brain lesions and quantify their recovery during the BECOME study.DESIGN/METHODS: T1-weighted images with and without a fat saturation pulse were acquired pre-treatment and monthly for 12-24 months after randomization. Experiments showed that percent difference fat saturation maps calculated from these images showed MTR contrast. Images were analyzed using a novel technique for measuring MTR changes over time. New MTR lesions were identified based on a drop in MTR signal that co-localized with a new T2 lesion, and MTR timecourses in that tissue before and after lesion formation were constructed. Differences in these timecourses due to the two treatments were modeled using a general linear random effects model.RESULTS: Acute decrease in MTR associated with MTR lesion formation was followed by partial recovery to a stable level. This level was significantly greater in new MTR lesions from patients randomized to GA (p<0.0001). This difference was smaller, but still significant when the recovery of MTR was analyzed in new gadolinium-enhancing lesions detected using the highly sensitive triple-dose, delayed, 3T BECOME protocol.CONCLUSIONS: We identified a novel type of lesion based on acute decreases in MTR, a marker of myelin density, and quantified the stable level to which MTR recovered in these lesions in BECOME study MS patients. Subjects randomized to GA showed significantly greater stable recovery levels of MTR, consistent with greater new MTR lesion repair and possibly remyelination.Supported by: The BECOME study was supported by Bayer Schering Pharma, distributors of IFN-1b, but was investigator-initiated and remains the intellectual property of New Jersey Medical School/University of Medicine & Dentistry of New Jersey.Disclosure: Dr. Brown has received personal compensation for activities with NeuroRx Research. Dr. Cook has received personal compensation for activities with Merck Serono, Bayer Healthcare, Sanofi-Aventis Pharmaceuticals, Inc., Neurology Reviews, Biogen Idec, Teva Neuroscience, and Actinobac Biomed Inc. Dr. Cadavid has received personal compensation for activities with Biogen Idec as an employee. Dr. Wolansky has nothing to disclose. Dr. Narayanan has received personal compensation for activities with Teva Neuroscience and NeuroRx Research. Dr. Arnold has received personal compensation or research support from Bayer Healthcare, Biogen Idec, Genetech, NeuroRx Research, Roche, Schering, Serono, and Teva Neuroscience. Dr. Arnold has received personal compensation or research support for Bayer Healthcare, Biogen Idec, Genetech, NeuroRx Research, Roche, Schering, Serono, and Teva Neuroscience.