AVONEX® Combination Trial - "ACT"

Inclusion Criteria: * Age 18 to 55, inclusive * Diagnosis of MS * A relapsing-remitting course * Expanded Disability Status Scale (EDSS) score 0.0-5.5 inclusive at Baseline * Currently receiving AVONEX® therapy * Treated with AVONEX® for at least 6 consecutive months prior * Breakthrough disease (clinical relapse or gadolinium-enhancing MRI lesion) during the prior 12 months, at least 6 months after initiating AVONEX therapy. Exclusion Criteria: * History of cirrhosis, chronic hepatitis, or currently active hepatitis * History of poorly-controlled hypertension, diabetes mellitus, or peptic ulcer disease * History of aseptic bone necrosis, osteoporosis, or osteoporosis-related bone fracture * History of steroid-induced psychosis. * History of or abnormal laboratory results indicating significant illness * History of severe allergic or anaphylactic reactions or known drug hypersensitivity or intolerance to MTX, IVMP, or AVONEX®. * History of allergy to albumin * History of any episode of suicidal ideation or severe depression within 3 months of the Screening Visit. * History of seizure within 3 months prior to the Screening Visit. * Diagnosis of primary progressive, secondary progressive, or progressive relapsing MS * MS relapse with onset within 60 days prior to the Baseline Visit * Any metallic or electronic material or device in the body, or condition that precludes the subject from undergoing MRI with gadolinium administration * A clinically significant infectious illness (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days of the Screening Visit * Abnormal blood tests, performed at the Screening Visit, which exceed any of the limits defined by the study.