Rationale Relapses remain a key outcome measure in multiple sclerosis (MS), are targeted by disease- modifying therapies (DMT), and guide treatment. As DMT prescribing continues to increase, it remains unclear what effect this has had on relapse frequency and phenotype over time.

Aim To examine relapse patterns using 20 years of longitudinal data and correlate with DMT use.

Method Prospectively collected relapse data from the South Wales MS registry was analysed from 2000- 2020. Relapse rate and phenotype according to DMT use were analysed across time epochs.

Results Of 6,165 relapses in 1,460 patients; 76% were in females and 15% occurred on DMT. Annualised relapse rates (ARR) showed a decreasing trend from 2000 (ARR=0.23) to 2020 (ARR=0.08). Using cross- sectional analysis of data from years 2005 versus 2020, rates of DMT exposure increased from 6% to 31%, and ARR was significantly associated with DMT use (p<0.01). Polysymptomatic relapses and relapses associated with full recovery, were both more likely to occur in people on DMT.

Conclusion Increasing use of DMTs was associated with decreasing ARR in this population-based MS cohort over 20 years. We also demonstrate that relapses occurring on DMTs appear to be associated with more favourable recovery.