No evidence of disease activity 3 and 4 (NEDA-3 and NEDA-4) in RMS patients treated with ozanimod were evaluated. Data were gathered from a randomized phase 3 trial (RADIANCE, NCT02047734) comparing oral ozanimod 0.92 mg/d to intramuscular interferon Beta-1a (IFN) 30 µg/wk and an open-label extension trial (DAYBREAK, NCT02576717) comparing ozanimod 0.92 mg/d. In both studies, MRIs were done at the start and once a year. To control for high lesion activity and brain volume loss rates immediately after treatment initiation, NEDA-3 (no new gadolinium-enhancing lesions, no new/enlarging T2 lesions, no relapses, and no EDSS progression from baseline) and NEDA-4 (NEDA-3 plus annualized whole brain volume loss ≤0.4%) were calculated from RADIANCE baseline and rebaseline to RADIANCE month 12. (observed cases). NEDA-3 rates were 31.2%, 24.6%*, 16.2%*, 13.4%*, and 10.7% with continuous ozanimod and 26.9%, 17.0%, 9.8%, 8.6%, and 7.4% for those on/transitioned from IFN at RADIANCE months 12 and 24 and DAYBREAK months 12, 24, and 36, respectively. Continuous ozanimod rates were 21.5%, 14.0%*, 10.0%, 10.4%, and 10.3% whereas those on/transitioning from IFN rates were 16.3%, 7.8%, 5.9%, 6.2%, and 6.3%. After rebasing to month 12, the NEDA-3 rates at RADIANCE month 24 and DAYBREAK month 12, 24, and 36 were 52.6%*, 33.1%*, 26.3%*, and 21.3% with continuing ozanimod, and 33.4%, 20.5%,17.4%, and 14.8% for those on/transitioned from IFN. For continuous ozanimod, rebaseline rates of NEDA-4 were 33.5%*, 20.0%*, 16.7%, and 14.1%, and for those on/transitioned from IFN, 19.7%, 11.7%, 11.2%, and 11.0%. When ozanimod was compared to IFN, more patients achieved NEDA-3 and NEDA-4 at month 24. More patients on continuous ozanimod vs transitioned from IFN achieved NEDA-3 and NEDA-4 in DAYBREAK after rebasing to month 12.