By Nils Koch-Henriksen,Per Soelberg Sørensen,Melinda Magyari Jun 14, 2021 Whether relapses have direct effects on permanent disability in multiple sclerosis is still an unsettled issue. We aimed at investigating the cumulative effect of breakthrough relapses on the Expanded Disability Status Scale (EDSS) in relapsing-onset MS patients under disease modifying therapy (DMT). From the Danish Multiple Sclerosis Registry we identified all patients in Denmark with relapsing-onset MS who had started DMT and followed them from the first day of treatment. We included patients aged 18-59 with Kurtzke’s EDSS score 6.0 at entry, and we compared patients with and without relapses during follow-up. Endpoints were 1) annualized increase in EDSS; 2) time to 6-month sustained EDSS-worsening; 3) time to EDSS 6.0; and 4) time to increase in pyramidal- and cerebellar functional systems. Patients with and without relapses after entry were 1:1 matched by sex, EDSS, and age at entry. We analysed EDSS-worsening with adjusted Generalized Linear Models and time to the endpoints with adjusted Cox regression.