OBJECTIVES: To compare direct medical costs for patients with relapsing-remitting multiple sclerosis (RRMS) treated with subcutaneous (sc) IFNβ1a 44mcg three times weekly (TIW) versus other interferon-beta (IFNβ) therapies across endpoints comprising the “no evidence of disease activity” (NEDA) measure. METHODS: A decision-analytic model was developed using comparative efficacy data sourced from a network meta-analysis (NMA) of IFNβ therapies: scIFNβ1a 44mcg TIW, scIFNβ1b 250mcg every other day, intramuscular (im) IFNβ1a 30mcg once weekly, and pegylated (peg) IFNβ1a 125mcg every two weeks. The number of patients experiencing NEDA-related endpoints (relapse, new MRI activity, or disability progression) for each therapy was determined using risk ratios derived from odds ratios (ORs) vs. placebo (pairwise analysis) or vs. other IFNβ therapies (NMA analysis). The model followed 1,000 patients with RRMS over 2 years. Costs were sourced from the literature. One-way sensitivity analyses (OWSAs) were performed to test the robustness of the results. RESULTS: Only medical costs were assessed, thus observed cost-offsets meant fewer patients experienced NEDA-related endpoints. For scIFNβ1a 44mcg vs. pegIFNβ1a, results from the pairwise analysis projected cost-offsets of $893,652 (relapse) and $252,219 (MRI); results from the NMA also projected cost-offsets of $578,174 (relapse), $15,628 (disability), and $105,667 (MRI). For scIFNβ1a 44mcg vs. imIFNβ1a, results from the pairwise analysis projected cost-offsets of $755,737 (relapse) and $239,926 (MRI); results from the NMA also projected cost-offsets of $525,511 (relapse), $118,716 (disability), and $110,435 (MRI). For scIFNβ1a 44mcg vs. scIFNβ1b, results from the pairwise analysis projected cost-offsets of $84,826 (relapse) and $32,435 (disability); results from the NMA also projected a cost-offset of $35,948 (disability). OWSAs confirmed substantial cost-offsets for the comparisons examined. CONCLUSIONS: The results of this decision-analytic model suggests that scIFNβ1a 44mcg provides substantial cost-offsets versus other IFNβ treatments across NEDA-related endpoints.