A Multicenter Randomized Blinded Parallel Group Study of AVONEX in Combination with Oral Methotrexate Intravenous Methylprednisolone or Both in Subjects with Relapsing Remitting Multiple Sclerosis Who Have Breakthrough Disease on Avonex Montherapy

Primary Objectives: . To determine whether adding weekly oral methotrexate (MTX) to the standard regimen of AVONEX@alone or the standard regimen of AVONEX@plus every other month intravenous methylprednisolone (IVMP) is effective in reducing the relapse rate per subject-year over a 24-month observation period in subjects with relapsing-remitting multiple sclerosis (RR-MS). . To determine whether adding every other month IVMP to the standard re~imen of AVONEX@alone or the standard regimen of AVONEX plus weekly oral MTX is effective in reducing the progression of whole brain atrophy over a 24-month period, as measured by percent change in brain parenchymal fraction (BPF) from Baseline to Month 24, in subjects with RR-MS. Secondary Obiectives: To determine whether adding weekly oral MTX to the standard regimen of AVONEX@alone or the standard regimen of AVONEX@ plus every other month intravenous IVMP is effective in: . Reducing the progression of functional impairment, as measured by Baseline to Month 24 change in the Multiple Sclerosis Functional Composite (MSFC). . Reducing lesion activity on brain magnetic resonance imaging (MRI), as measured by the combined number of T2-hyperintense lesions at Month 24 that are new or enlarged since Baseline. . Reducing the progression of whole brain atrophy over a 24-month period, as measured by percent change in the BPF from Baseline to Month 24. To determine whether adding every other month IVMP to the standard regimen of AVONEX@alone or the standard regimen of AVONEX@ plus weekly oral MTX is effective in: . Reducing the relapse rate per subject-year over a 24-month observation period. . Reducing the progression of functional impairment, as measured by Baseline to Month 24 change in the MSFC. . Reducing lesion activity on brain MRI, as measured by the combined number of T2-hyperintense lesions at Month 24 that are new or enlarged since Baseline.