Background: Over the past two and a half decades, there has been an exponential increase in FDA approvals of treatments for relapsing forms of multiple sclerosis (RMS), requiring neurologists and patients to make comparative decisions with limited head-to-head trials. To remedy this deficiency, there has been an interest in using the inverse of absolute risk reduction (number needed to treat or NNT) rather than simply reporting relative risk reduction. More recently, teriflunomide, a daily oral MS disease modifying treatment (DMT), has emerged as the active comparator in several clinical trials of oral, self-injectable and intravenous DMTs. NNT for teriflunomide as compared to the three most recently studied MS DMTs has not been previously reported. Objectives: To perform a NNT analysis of recent teriflunomide-controlled clinical trials in MS. Methods: NNT to prevent 1 relapse is the inverse of absolute risk difference in Annualized Relapse Rates (ARR) between experimental and control groups. Data on ARR was obtained from the reported pivotal clinical trials of ofatumumab (ASCLEPIOS I/II, NCT02792218/NCT02792231), ponesimod (OPTIMUM, NCT02425644), and ublituximab (ULTIMATE I/II, NCT03277261/NCT03277248). Since one cannot treat a fraction of a patient, NNTs are rounded-up to a whole number. Results: The NNT for one patient to avoid a relapse while treated with ofatumumab (instead of teriflunomide) is 10 (9.09) and 7 (6.67) from ASCLEPIOS I and II, respectively. The NNT for one patient to avoid a relapse while treated with ponesimod (instead of teriflunomide) is 12 (11.36) from OPTIMUM. The NNT for one patient to avoid a relapse while treated with ublituximab (instead of teriflunomide) is 9 (8.93) and 12 (11.49) in ULTIMATE I and II, respectively. Conclusions: Unbridled enthusiasm for top-line results of primary endpoints of recent clinical trials should be tempered by simplified evidence-based techniques in assessing absolute differences in study endpoints. NNT itself is limited by clinical trial differences, and there is an increasing need to develop novel techniques to compare the efficacy of MS DMTs across clinical trials.