Environmental Factors Associated with Disease Progression after the First Demyelinating Event: Results from the Multi-Center SET Study (P05.134)

OBJECTIVE: To investigate the associations of environmental MS risk factors with clinical and MRI measures of progression in high-risk clinically isolated syndromes (CIS) after the first demyelinating event. BACKGROUND: The first clinical demyelinating event represents a crucial opportunity for understanding the factors involved in conversion to multiple sclerosis (MS). The environmental factors in CIS have not been extensively investigated prospectively and their role in MS disease course and progression is not well characterized. DESIGN/METHODS: We analyzed 211 CIS patients (age: 28.9 ± 7.8 years) enrolled in the SET study, a multi-center study of high-risk CIS patients. Pre-treatment samples were analyzed for IgG antibodies against cytomegalovirus (anti-CMV), Epstein Barr virus (EBV) early nuclear antigen-1 (EBNA-1), viral capsid antigen (VCA), early antigen-diffuse (EA-D), 25 hydroxy-vitamin D3 and cotinine levels and HLA DRB1*1501 status. The inclusion criteria required evaluation within 4 months of the initial demyelinating event, 2 or more brain MRI lesions and the presence of two or more oligoclonal bands in cerebrospinal fluid. All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24 months. RESULTS: The time to first relapse decreased and the number of relapses increased with anti-CMV IgG positivity. Smoking was associated with increased number and volume of contrast-enhancing lesions (CEL) during the 2-year period. The cumulative number of CEL and T2 lesions during the 2-year period was greater for individuals in the highest quartile of anti-EBV VCA IgG antibodies. The percent loss of brain volume was increased for those in the highest quartile of with anti-EBV VCA IgG antibodies. CONCLUSIONS: Relapses in CIS patients were associated with CMV positivity whereas anti-EBV VCA positivity was associated with progression on MRI measures, including accumulation of CEL and T2 lesions and development of brain atrophy. Supported by: Czech Ministries of Education and Health [NT13237-4/2012, MSM 0021620849, PRVOUK-P26/LF1/4, RVO-VFN64165/2012]. The SET study received research support from Biogen Idec Inc. MRI acquisition was supported by Biogen Idec. Disclosure: Dr. Horakova has received personal compensation for activities with Biogen Idec, Novartis, Merck Serono, Teva Neuroscience, and Bayer. Dr. Horakova has received research support from Biogen Idec. Dr. Zivadinov has received personal compensation for activities with Teva Neuroscience, Biogen Idec, Serono, Inc., Genzyme Corporation, Sanofi-Aventis Pharmaceuticals, Inc., Bayer Pharmaceuticals, Questcor Pharmaceuticals and Novartis as a speaker and/or consultant. Dr. Zivadinov has received research support from Biogen Idec, Teva Neuroscience, Novartis, Genzyme Corporation, Sanofi-Aventis Pharmaceuticals, Inc., Bracco, Questcor Pharmaceuticals and Serono, Inc. Dr. Weinstock-Guttman has received personal compensation for activities with Acorda Therapeutics, Biogen Idec, Serono Inc., Novartis, Pfizer, Inc., Teva Neuroscience and Genentech, Inc. as a speaker and/or participant on an advisory board. Dr. Weinstock-Guttman has received research support from the National Multiple Sclerosis Society, the National Institutes of Health, ITN, Teva Neuroscience, Biogen Idec, Serono Inc., Aspreva-Roche, Acorda Therapeutics & Cognition, Shire Pharmaceuticals Group and Novartis. Dr. Havrodova has received personal compensation for activities with Bayer, Biogen Idec, Genzyme Corporation, GlaxoSmithKline, Inc., Novartis, Merck & Co., Inc., Sanofi-Aventis Pharmaceuticals, Inc., Serono, and Teva Neuroscience. Dr. Qu has received research support from the Department of Defense, the National Science Foundation, the National Institutes of Health, the American Heart Association, Kinex, CH3, Pfizer Inc, Novartis, Abbott, and Amgen Inc. Dr. Tamano-Blanco has nothing to disclose. Dr. Badgett has nothing to disclose. Dr. Tyblova has received personal compensation for activities with Biogen Idec, Sanofi-Aventis Pharmaceuticals, Inc., Teva Neuroscience, and Merck Serono. Dr. Tyblova has received research support from Biogen Idec. Dr. Bergsland has nothing to disclose. Dr. Hussein has nothing to disclose. Dr. Willis has nothing to disclose. Dr. Krasensky has received research support from Biogen Idec. Dr. Vaneckova has received research support from Biogen Idec. Dr. Seidl has received research support from Biogen Idec Inc. Dr. Dwyer has nothing to disclose. Dr. Duan has nothing to disclose. Dr. Kalincik has received personal compensation for activities with Biogen Idec, Sanofi Aventis, Teva, and Merck-Serono. Dr. Ramanathan has received personal compensation for activities with Serono Inc., Biogen Idec, Allergan, Inc., Netezza, Pfizer, Novartis, the National Multiple Sclerosis Society, the Department of Defense, Jog for the Jake Foundation and the National Institutes of Health as a consultant. Dr. Ramanathanhas received personal compensation in an editorial capacity for American Association of Pharmaceutical Scientists. Dr. Ramanathan has received research support from Serono Inc., Biogen Idec, Allergan Inc., Netezza, Pfizer, Novartis, the National Multiple Sclerosis Society, the Department of Defense, Jog for the Jake Foundation, the National Institutes of Health.