Natalizumab strongly suppresses cortical pathology in relapsing–remitting multiple sclerosis

Abstract

Background: Since cortical pathology has been indicated to play a relevant role in the physical and cognitive disability of multiple sclerosis (MS) patients, this study aims to analyze the efficacy of natalizumab in slowing down its progression. Methods: A total of 120 relapsing–remitting MS patients completed a 2-year prospective study: 35 received natalizumab, 50 received interferon beta-1a or glatiramer acetate (immunomodulatory agents - IMA) and 35 remained untreated. Forty healthy subjects constituted the reference population. Clinical and magnetic resonance imaging (MRI) evaluations (including cortical lesions and atrophy) were performed at baseline and after 2 years. Results: Natalizumab significantly reduced accumulation of new cortical lesions (0.2±0.6,range 0–3) compared to immunomodulatory agents (1.3±1.1 togli spazio, range 1–6, p=0.001) and no treatment (2.9±1.5, range 1–8, p<0.001). The percentage of patients with new cortical lesions was also lower in natalizumab-treated patients (20%) compared to IMA-treated and untreated patients (68.0% and 74.2%; p<0.001 for both comparisons). Furthermore, the progression of cortical atrophy was significantly reduced by natalizumab (% change=1.7%) compared to IMA (3.7%, p=0.003) and no therapy (4.6%, p<0.001). Finally, a greater percentage (51.4%) of natalizumab-treated patients remained disease-free (no clinical or MRI evidence of disease activity or progression) compared to IMA-treated (18%, p=0.001) and untreated patients (5.7%, p<0.001). Conclusions: Natalizumab treatment significantly decreases cortical lesion accumulation and cortical atrophy progression in severe relapsing–remitting MS. While supporting the inflammatory origin of cortical lesions, our results highlight the significant impact of natalizumab on cortical pathology.