Background: The number of disease-modifying therapies (DMTs) within the S1P receptor modulator and fumarate classes has expanded with recent approvals of siponimod (BAF) and diroximel fumarate (DRF), respectively. Objectives: To compare multiple sclerosis (MS) treatment patterns and therapy selection decisions between DMTs with similar mechanisms of action (MOA). Methods: In February 2020, US neurologists contributed chart reviews for a retrospective, cross-sectional audit of MS patients switched to a new DMT within the prior three months (n=204 physicians; n=1,009 charts). Analyzed data include patients switched to fingolimod (FTY; n=93), BAF (n=38), dimethyl fumarate (DMF; n=113), and DRF (n=12). Results: Within the S1P class, more patients switched to BAF were diagnosed with active secondary progressive MS (SPMS; 34% vs. 10%) or primary progressive MS (PPMS; 13% vs. 1%) compared to those switched to FTY. Among relapsing-remitting MS patients, anticipated near-term transition to SPMS did not differ between DMTs (21% vs. 11%). Product familiarity (3% vs. 37%) was more influential in FTY selection, while specific comorbidity (11% vs. 2%) and active SPMS indication approval (24% vs. 2%) were more influential in BAF selection. Monitoring (3% vs. 8%) and initiation ease (11% vs. 19%) influence did not differ by S1P agent. Ocrelizumab (29% vs. 13%) and cladribine (16% vs. 2%) were more often, and DMF (8% vs. 37%) less often, considered the alternative option for BAF than for FTY. Fewer BAF switches followed only one prior failure (61% vs. 82%). BAF versus FTY switches were less likely from interferons (5% vs. 25%) and glatiramer acetate (24% vs. 50%) and more likely from oral (47% vs. 18%) and monoclonal antibody (24% vs. 8%) DMTs. Fumarate switch data show that tolerability (67% vs. 27%) is more influential in DRF selections, while familiarity (8% vs. 37%) and administration type preference (8% vs. 46%) are more impactful during DMF selections. Patients treated with DRF more frequently switched from another oral DMT (58% vs. 14%), most commonly DMF. Switch pattern comparisons within classes will be updated with 2021 data, including the addition of generic DMF, monomethyl fumarate, and ozanimod. Conclusions: Recent switch patterns to DMTs sharing similar MOA are differentially influenced by attributes related to time on market for established DMTs versus the focus of the respective clinical development program for second-to-class DMTs disability progression in SPMS for BAF and improved tolerability for DRF.