Disclosed herein are methods in which an individual with multiple sclerosis (MS) can be classified into one of six subject groups, each subject group predictive for the patient's responsiveness to an interferon-β (IFN-β) therapy. The individual with MS can be classified according to the individual's serum marker levels, e.g., at baseline or following treatment with therapy. Depending on the classification, the individual with MS can be treated with standard therapies (e.g. IFN-β) or one or more alternative therapies with or without IFN-β.