EDSS Changes in CombiRx: Blinded, 7-Year Extension Results for Progression and Improvement (P04.121)

OBJECTIVE: Evaluate the changes in EDSS, for both worsening and improvement, in up to 7 years of follow up in the primary (3 year) and extension phases (4-7 years) of the CombiRx trial. BACKGROUND: CombiRx was a double-blind, placebo-controlled, multi-center randomized clinical trial comparing combined interferon beta-1a (IFN) 30ug IM weekly and glatiramer acetate (GA) 20mg daily to each agent alone in relapsing-remitting multiple sclerosis (RRMS). Entry criteria, demographics and the three year clinical and MRI results have been previously presented. DESIGN/METHODS: 1008 participants were randomized and followed until the last participant enrolled completed 3 yrs. At trial completion, 80.1% completed 3 years and 84.4% continued into the extension. Confirmed progression/improvement (CP/CI) was defined as a 1 point increase/decrease in EDSS sustained for 6 months. RESULTS: Average follow up time was 3.9 years (0-6.9 range) and was not different by treatment. Over the 7 years, 29.7% of participant experienced CP; IFN+GA: 29.5%, IFN: 28.2%, GA: 31.7% (IFN vs GA p=0.40, IFN+GA vs IFN p=0.37, IFN+GA vs GA p=0.27). Conversely, CI occurred in 26.0%; IFN+GA: 29.5%, IFN: 28.2%, GA: 31.7% (IFN vs GA p=0.40, IFN+GA vs IFN p=0.37, IFN+GA vs GA p=0.27). During their time on trial, 1.9% of all participants experienced CP and CI (CP+/CI+), 24.1% were CP-/CI+ (p CONCLUSIONS: Often clinical results focus on confirmed progression. As shown here, slightly more experience CP (29.7%) as CI (26.0%). There was no difference across treatment groups. Without a full placebo group, we cannot estimate an overall treatment effect of either metric but can determine that these metrics can be used to look at both improvement and worsening, which can aide design of repair studies. Supported by: NIH/NINDS (5U01NS045719). Disclosure: Dr. Lublin has received personal compensation for consulting from Bayer HealthCare Pharmaceuticals, Biogen Idec, EMD Serono Inc., Novartis, Pfizer, Teva Neuroscience, Genmab, Medicinova, Actelion, Sanofi-Aventis, Acorda, Questcor, Roche, Celgene, Abbott, Johnson & Johnson, Revalesio, Coronado Bioscience, and GenFL. Dr. Lublin has received compensation from Elsevier for serving as Co-Chief Editor of Multiple Sclerosis and Related Diseases. Dr. Cofield has received personal compensation for activities with Teva Neuroscience, Orthotech Biotech, the American Academy for Orthopedic Surgery, and MedImmune. Dr. Cutter has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc., Cleveland Clinic, Daichi-Sankyo, GlaxoSmithKline Inc., Genmab Biopharmaceuticals, Eli Lilly & Company, Medivation, and Modigenetech. Dr. Cutter has received compensation for serving as the president of Pythagoras, INC. Dr. Cutter has received research support from various pharmaceutical corporations. Dr. Salter has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Conwit has nothing to disclose. Dr. Narayana has received personal compensation for activities with Teva Neuroscience. Dr. Nelson has received personal compensation for activities with Bayer, Biogen Idec, EMD Serono, National MS Society, MS Association of America, Novartis, Sanofi-Aventis Pharmaceuticals, Teva Neuroscience, and the University of Massachusetts. Dr. Nelson has received research support from Novartis and Sanofi-Aventis Pharmaceuticals, Inc. Dr. Gustafson has nothing to disclose. Dr. Wolinsky has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Genzyme Corporation, Hoffman LaRoche, Janssen Pharmaceutical, Novartis, Sanofi-Aventis Pharmaceuticals and Teva/Teva Neuroscience as a consultant. Dr. Wolinsky has received (royalty or license fee or contractual rights) payments from University of Texas. Dr. Wolinsky has received research support from Clayton Foundation for Research and the National Institutes of Health.