OBJECTIVES: Teriflunomide and dimethyl fumarate (DMF), oral therapies for relapsing-remitting MS, have demonstrated efficacy in clinical trials on magnetic resonance imaging and clinical outcomes. Despite challenges in comparing outcomes across studies, exploratory analyses of treatment effects can be compared informally using relative reductions in a specific endpoint. The number needed to treat (NNT) to prevent an event is an important outcome to consider for any comparisons within the field of MS. METHODS: NNTs were derived using data from studies with teriflunomide 14 mg (TEMSO, NCT00134563; TOWER, NCT00751881) or DMF (DEFINE, NCT00420212; CONFIRM, NCT00451451) based on the inverse of absolute differences between treatment and placebo groups. RESULTS: Teriflunomide studies included patients with progressive disease; patients in DEFINE had slightly lower baseline Expanded Disability Status Scale scores. Teriflunomide and DMF significantly reduced risk of relapse (all studies). NNTs to prevent 1 relapse were similar across all studies (5.9 [TEMSO], 5.6 [TOWER], 5.3 [DEFINE], 5.6 [CONFIRM]). Risk of disability progression sustained for 12 weeks was significantly reduced in TEMSO, TOWER, and DEFINE but not CONFIRM. Corresponding NNTs to prevent disability progression were 13.8, 17.4, 10.8, and 30.2. Risk of relapse leading to hospitalization was significantly reduced in TEMSO and TOWER but not in DEFINE and CONFIRM. Corresponding NNTs were lower in TEMSO (12.5) and TOWER (20) than in DEFINE (50) and CONFIRM (50). Safety data and corticosteroid use will be presented. CONCLUSIONS: Using the NNT approach, we demonstrate a comparable effect size for teriflunomide and DMF on relapses. NNTs to prevent disability progression with teriflunomide showed a consistent significant reduction in risk vs placebo in both TEMSO and TOWER. For DMF, comparable NNTs were observed only in DEFINE, and not in CONFIRM. Reduction of risk for relapse leading to hospitalization was significant only for teriflunomide.