Introduction: Without treatment multiple sclerosis (MS) is a degenerative disease from the outset. A number of therapies have shown significant effects on relapse rates and short-term disability outcome measures. Evidence of a long-term benefit on disability and brain atrophy outcomes remains sparse. With the aim of fill-ing this knowledge deficit, we have undertaken a retrospective case-control analysis of real-world data. Objectives/Aims: We aimed to compare relapse, disability and brain atrophy outcomes in a cohort of people with MS (pwMS) looking at ‘treated’ vs ‘untreated’ and two different approaches to treatment: ‘start high’ (monoclonal antibodies) vs ‘escalation’ (other therapies ± escalation, with aim of achieving NEDA).Methods: This was a retrospective, case-control study based on systematically collected case records using a bespoke MS database and electronic medical records systems at a single centre. Data included, age at onset, baseline clinical features, time to relapse, time to sustained EDSS 6.0 and duration of follow up. Annualised, percentage change in whole brain vol-ume from year 2 to last available MRI was available for a sub-set. Cox proportional hazard survival analysis and generalized linear models were used to adjust for baseline variables (sex, age at onset, baseline EDSS, initial ARR, T2 lesion load and decade).Results: Complete clinical information was available for 582 pwMS with mean follow up of 16.7 (±11.2) years Regression analysis indicated that sex, age of onset, decade and T2 lesion load were all predictive of long-term outcomes (MSSS). Survival anal-ysis of treated vs untreated (n=537) for relapse (HR 0.74, p=0.046) and for EDSS 6.0 (HR 0.31, p<0.,001) were both significant, in favour of treatment. In addition, annualised percentage change in whole brain atrophy was lower in the treated group (treated -0.084% vs untreated -0.343%; p<0.001). Survival analysis of start high vs escalation (n=412) for relapse (HR 0.47, p=0.001) was significant, in favour of start high. However, there was no significant difference for time to EDSS 6.0 with a low event rate for both groups at 14 years (mean = 5%).Conclusion: These real-world data indicate that current treatment of MS significantly reduces long-term disability and rate of brain atrophy. Starting with high efficacy therapy or an escalation with treatment to target approach are both associated with low levels of long-term disability (EDSS 6.0). We conclude that treatment of MS is having a significant impact on long-term outcomes. Disclosure of interest: No disclosures relevant to data collection or analysis