Assessment of the RoAD Score as a Predictor of Long-Term Irreversible Ambulatory Disability in Multiple Sclerosis: Evidence from a Real-World Cohort

<i>Background and Objectives</i>: In multiple sclerosis (MS), the Risk of Ambulatory Disability (RoAD) score is a validated prognostic tool based on demographic, clinical, and MRI variables assessed at treatment initiation and after one year. We aimed to assess the predictive value of the RoAD score for long-term irreversible disability in a large real-world MS cohort. <i>Materials and Methods</i>: A retrospective analysis was performed on relapsing-remitting MS patients (RRMS) followed for ≥5 years at the Bari MS Center. The RoAD score (0-8) was calculated and dichotomized (<4 vs. ≥4). Cox proportional hazards models were used to evaluate the risk of irreversible Expanded Disability Status Scale (EDSS) 6.0. <i>Results</i>: A total of 1051 RRMS patients (67.1% female) were included, with a median follow-up of 18.0 years. Most patients (97.5%) received moderate-efficacy DMTs as first-line therapy. During follow-up, 123 (11.7%) patients reached irreversible EDSS 6.0 after a median of 9.5 years. Patients with RoAD score ≥4 (16.8%) showed a threefold higher risk of irreversible disability (HR 3.16, 95% CI 2.19-4.56, <i>p</i> < 0.001). The predictive value of RoAD ≥4 was confirmed both in the adjusted multivariable model and in sensitivity analyses treating RoAD as a continuous variable. <i>Conclusions</i>: In this real-world cohort, the RoAD score demonstrated solid predictive validity for long-term ambulatory disability, supporting its role as a practical tool for early risk stratification in MS management.