Natalizumab strongly suppresses cortical pathology in relapsing-remitting multiple sclerosis

Mult Scler. 2012 Dec;18(12):1760-7. doi: 10.1177/1352458512447704. Epub 2012 May 8.

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.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Cerebral Cortex / pathology*
  • Disease Progression
  • Female
  • Glatiramer Acetate
  • Humans
  • Image Interpretation, Computer-Assisted
  • Immunologic Factors / therapeutic use
  • Interferon-beta / therapeutic use
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / pathology*
  • Natalizumab
  • Peptides / therapeutic use
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Immunologic Factors
  • Natalizumab
  • Peptides
  • Glatiramer Acetate
  • Interferon-beta