A method is provided for determining the efficacy of interferon -beta (IFN-â) therapy in a subject with multiple sclerosis. One step of the method can include obtaining a biological sample from the subject. After obtaining the biological sample, the expression level of at least one interferon-regulated gene (IRG) and/or variant thereof can be determined. Increased or decreased expression of the at least one IRG and/or variant thereof as compared to a control may indicate that the subject will respond poorly to IFN-â therapy.