OBJECTIVES: Self-injectable disease-modifying therapies (DMTs) are the first-line standard of care for relapsing-remitting multiple sclerosis (RRMS) in Scotland: Interferon beta (IFNβ)-1a (22mcg and 44mcg three times/week, and 30mcg once/week), IFNβ-1b 250mcg every other day, and glatiramer acetate (GA) 20mg once/day. Peginterferon beta-1a (PEG-IFN; 125mcg subcutaneous every two weeks) is a new DMT with less frequent dosing which may improve treatment adherence. The pivotal ADVANCE trial showed benefits of PEG-IFN versus placebo on relapses and disability progression, but its long-term clinical and economic consequences versus other DMTs are still unknown. This analysis assessed the cost-effectiveness of PEG-IFN versus self-injectable DMTs from the National Health System perspective in Scotland. METHODS: A Markov cohort economic model, published and accepted by health technology assessment authorities, was adapted for this analysis. The model predicts disability progression (measured by the Expanded Disability Status Scale [EDSS]) and occurrence of relapses and other adverse events (AEs), and translates them into quality-adjusted life-years and costs. The natural history data were obtained from the placebo arm of the ADVANCE trial extrapolated with data from the London, Ontario database for EDSS transition probabilities and from a large population-based MS survey for relapse rates. A network meta-analysis was conducted to estimate the comparative efficacy of each treatment versus placebo. Costs (in 2014 British Pounds) of drug acquisition, disease management, relapses, and AEs were from public databases and literature. Clinical and economic outcomes were projected over 30 years and discounted at 3.5% per year. RESULTS: Over 30 years, PEG-IFN yielded greater clinical benefits and cost savings compared with IFNβ-1a 22mcg IFNβ-1a 30mcg, and IFNβ-1b 250mcg. Compared with GA 20mg and IFNβ-1a 44mcg, the incremental cost-effectiveness ratios were £17,821 and £4,121, respectively. Deterministic and probabilistic sensitivity analyses confirmed that the results were robust.   CONCLUSIONS: PEG-IFN is a cost-effective treatment for patients with RRMS in Scotland.