Relapse Activity in the CombiRx Trial: Blinded, 7-Year Extension Results (S01.002)

OBJECTIVE: Evaluate annualized relapse rates (ARR) in up to 7 years of follow up in the core (3 years) 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. Exacerbation types were based on stringency of confirmation of EDSS change: Protocol Defined Exacerbation (PDE) within 7 days, Non-PDE (NPDE) outside 7 days. RESULTS: Average years on study was 3.9, not different by treatment. ARRs by treatment for PDE were IFN+GA: 0.10, IFN: 0.13, GA: 0.09; with age adjusted HR of 1.37 for IFN vs GA (p=0.03), 0.78 IFN+GA vs IFN (p=0.02), and 1.07 IFN+GA vs GA (p=0.32); and for PDE+NPDE were IFN+GA: 0.19, IFN: 0.25, GA: 0.18; with HR of 1.32 for IFN vs GA (p=0.01), 0.75 for IFN+GA vs IFN (p=0.001), and 1.01 for IFN+GA vs GA (p=0.45). CONCLUSIONS: This study provides the longest blinded phase III RRMS follow up results. The 3-year ARR results previously reported were low for all treatment cohorts with the combination and GA groups having the lowest ARR. Similar patterns are seen in this long term extension cohort. Relapse rates drop over the course of the study to exceedingly low values. Both the combination group and GA continue to be superior to IFN. In the core study, MRI activity was significantly higher in the combination group. Despite that, long term follow up did not reveal a delayed clinical benefit in the combination group. 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.