IntroductionThe TYSABRI Observational Program (TOP) is an ongoing observational study of natalizumab treatment in relapsing-remitting multiple sclerosis (RRMS) patients. Country-specific data on relapse and disability outcomes, alongside global data, can provide information on natalizumab’s effectiveness in local practice.MethodsAnnualised relapse rate (ARR) was analysed in TOP UK (n=134) and global (N=6321) cohorts using data from July 2007 to November 2022. Cumulative probabilities of 24-week confirmed disability worsening (CDW) and improvement (CDI) were analysed in each cohort.ResultsARR decreased in UK patients from 2.21 in the year before initiation to 0.15 on natalizumab (P<0.0001), consistent with a global decrease from 2.00 to 0.18 (P<0.0001). ARR in subgroups based on number of prior disease modifying therapies and baseline Expanded Disability Status Scale scores will be presented. At 10 years follow-up, cumulative probability of CDI was 46.3% and 35.2% in the UK and global cohorts, respectively; cumulative probability of CDW was 60.3% and 40.7%.ConclusionsThe reduction in ARR on natalizumab was similar in the TOP UK and global cohorts, with the cumulative probability of CDI and CDW higher in the UK cohort. These findings support the real-world effectiveness of natalizumab.Support: Funded by Biogen. Disclosures: Included on the poster.