MRI Outcomes in CombiRx: Blinded, 7-Year Extension Results

OBJECTIVE: To assess MRI parameters over 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). MRIs were done at baseline, and planned at 6 months, years 1-4, 6 and at study termination; three year results were presented. DESIGN/METHODS: 1008 participants were followed until the last participant enrolled completed 3 yrs; 80.1% completed 3 years and 84.4% continued into the extension. At least one extension MRI was assessed for numbers of enhanced, and unenhanced new or substantially enlarged T2 lesions (combined unique activity, CUA), total lesion volumes and their strictly T2 and T1 components, and atrophy for 84.1% of trial subjects. Proportions are for those with MRI at that time period. RESULTS: MRI characteristics at years 4, 5 and 6: 13.2%, 9.5% and 3.7% of participants had enhancements at the respective years. Median total lesion volumes were 6.8 ml at year 4 and 6.6 ml at year 6. Cumulative CUA free by treatment arm at year 4 for IFN+GA: 48.1%, IFN 30.9%, GA 30.8% (IFN vs GA p=0.67, IFN+GA vs IFN p=0.0007). Mean change in total lesion volume at year 4 for IFN+GA: -1.57, IFN -0.25, GA: 0.46 (IFN vs GA p=0.22, IFN+GA vs IFN p=0.04). Data for T2-hyperintense and T1-hypointense lesion components and global tissue loss will be presented. CONCLUSIONS: These results suggest that the stabilization of acute and more chronic measures of MRI-defined disease activity and tissue loss observed over the first three years of the trial continued on extended therapy in all three treatment arms. Reduced activity changes appeared more robust for those subjects initially randomized to combined therapy.