MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS

Background: In a 2-year, placebo-controlled trial ( the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis [ AFFIRM] study), involving 942 patients with relapsing multiple sclerosis ( MS), natalizumab significantly reduced the relapse rate by 68% and progression of sustained disability by 42% vs placebo. We report the effect of natalizumab on MRI measures from the AFFIRM study. Methods: The number and volume of gadolinium (Gd)-enhancing, new or enlarging T2-hyperintense, and new T1-hypointense lesions and brain parenchymal fraction were measured from annual scans obtained at baseline, 1 year, and 2 years. Results: Compared with placebo, natalizumab produced a 92% decrease in Gd-enhancing lesions ( means 2.4 vs 0.2; p < 0.001), an 83% decrease in new or enlarging T2-hyperintense lesions ( means 11.0 vs 1.9; p < 0.001), and a 76% decrease in new T1-hypointense lesions ( means 4.6 vs 1.1; p < 0.001) over 2 years. Median T2-hyperintense lesion volume increased by 8.8% in the placebo group and decreased by 9.4% in the natalizumab group ( p < 0.001); median T1-hypointense lesion volume decreased by 1.5% in the placebo group and decreased by 23.5% in the natalizumab group ( p < 0.001). Brain atrophy was greater in year 1 and less in year 2 in natalizumab-treated patients. Conclusion: Natalizumab has a sustained effect in preventing the formation of new lesions in patients with relapsing multiple sclerosis.