Predictors of Radiological and Clinical Disease Reactivation in Multiple Sclerosis Patients After Cessation of Natalizumab (Tysabri)

Background and Purpose : Natalizumab (NTZ) is widely used for patients with highly active relapsing–remitting multiple sclerosis (RRMS), but its discontinuation can lead to disease reactivation, significantly impacting Middle Eastern populations. This study aimed to assess the frequency of disease reactivation post‐NTZ discontinuation and identify possible demographic predictors. Methods : In this retrospective single‐center study, 171 patients with RRMS who received at least six consecutive NTZ infusions were analyzed. Clinical and radiological data were sourced from the AMIR registry. Binary and multivariate regression analyses were performed to identify factors associated with reactivation risk after 1 year, with a subset undergoing brain magnetic resonance imaging (MRI) segmentation and volumetric assessments. Results : Among 92 eligible patients, 16 (17%) showed disease reactivation. Prolonged washout periods (>3 months) significantly increased reactivation risk (hazard ratio [HR] 1.015, 95% CI 1.007–1.022, p < 0.001), whereas higher Expanded Disability Status Scale (EDSS) scores correlated with a reduced risk (HR 0.492, 95% CI 0.280–0.866, p < 0.014). In the subset of cases that underwent brain MRI segmentation, higher NTZ infusion numbers and delayed bridging therapy initiation were linked to increased reactivation risk. Conclusion : NTZ discontinuation requires thorough clinical evaluation for bridging therapy, yet optimal strategies remain undefined. Early bridging therapy initiation may mitigate reactivation, highlighting the need for further research on predictive factors and disease‐modifying therapy efficacy.