BackgroundReal-world, long-term adherence and effectiveness data is vital to complement our under- standing of therapies, which is often based on short-term clinical trials. Here we explored disease modifying therapy (DMT) durability in a UK-wide cohort of people with Multiple Sclerosis (pwMS).MethodsIn this cohort study, which included 4,415 pwMS from 10 UK MS centres, 6,960 DMT prescrip- tions were included in the analysis (mean 1.7, range 1-6 per patient). Prescriptions without accurate start dates were excluded (n=90). Kaplan-Meier survival analysis was used to model DMT persistence (days from prescription start to stop), which was used to calculate 2, 5 and 10-year durability (% of prescrip- tions continuing).ResultsTwo-year durability was highest for immune reconstitution therapies cladribine (98%), ocrelizumab (96%), and alemtuzumab (95%). Oral therapies fingolimod (74%) and dimethyl fumarate (73%), and intravenous natalizumab (78%) shared similar durability. Injectable therapies glatiramer acetate (51%) and interferon (55%), had lowest durability. Potential confounding factors include variable date of DMT licensing, change in DMT algorithms over time and increasing DMT options.ConclusionThis multi-centre study has revealed highly variable durability between DMTs over time, which may impact real-world effectiveness. These results may inform DMT clinical decision-making and improve outcomes for pwMS.