A double-blind placebo-controlled trial evaluating the efficacy of antibodies to IFN-γ and TNF-α in active SPMS found that blockade of IFN-γ, but not TNF-α, leads to reduced disability scores, decreased numbers of active lesions, and systemic cytokine changes including increased TGF-β production and a decrease in IL-1β, TNF-α, and IFN-γ concentrations [52]. This evidence concerns the gene IFNG and secondary progressive multiple sclerosis.