Effect of natalizumab on brain atrophy and disability progression in multiple sclerosis patients over 5 years

R. Zivadinov, D. Hojnacki, N. Bergsland, C. Kennedy, J. Hagemeier, R. Melia, D. P. Ramasamy, J. Durfee, E. Carl, M. G. Dwyer, B. Weinstock-Guttman

Research output: Contribution to journalArticlepeer-review

Abstract

Background and purpose: The long-term benefit of natalizumab on brain atrophy progression in multiple sclerosis (MS) patients is unknown. Our aim was to investigate its effect over 5 years. Methods: This prospective study included 60 relapsing MS patients who started natalizumab treatment in years 2006-2007. Results: At the 5-year follow-up, 20 patients discontinued natalizumab after an average of 29.5 cycles, 27 continued natalizumab treatment with some periods of honeymoon (average of 38.4 infusions) and 13 never stopped natalizumab (average of 60.6 infusions). In multiple linear regression analysis, adjusted for age, sex and baseline magnetic resonance imaging (MRI) status, the number of natalizumab infusions was associated with decrease of relapse rate (adjusted P = 0.037), but no association was found with the progression of disability, accumulation of lesion burden or brain volume loss. However, only one (8%) patient in the continuous monthly group experienced disability progression compared to 10 (37%) in the non-continuous and seven (35%) in the discontinuation natalizumab groups. At the follow-up, two patients had died [one from a fatal case of progressive multifocal leukoencephalopathy (PML) and one from a car accident] and 15 patients were lost to follow-up. There was another case of non-fatal PML over the follow-up. Conclusions: In line with previous reports, MS patients with longer and continuous use of natalizumab had fewer relapses and remained stable in their disability status. No difference in lesion burden accumulation or brain atrophy development was found in relation to the duration of natalizumab use. PML occurred in 2.5% of patients in this small sample cohort. Given the increased risk of PML and uncertain benefit of prolonged natalizumab use on clinical and MRI outcomes of disease progression found in this study, a careful risk-benefit therapeutic assessment is mandatory.

Original languageEnglish
JournalEuropean Journal of Neurology
DOIs
Publication statusPublished - Jun 2016

Keywords

  • Brain atrophy
  • Disability progression
  • Lesion burden
  • Magnetic resonance imaging
  • Multiple sclerosis
  • Relapse rate

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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