Natalizumab discontinuation in patients with multiple sclerosis: Profiling risk and benefits at therapeutic crossroads

Mult Scler. 2015 Nov;21(13):1713-22. doi: 10.1177/1352458515570768. Epub 2015 Feb 19.

Abstract

Objective: The objective of this paper is to estimate the risk of reaching well-established disability milestones after withdrawal of natalizumab (NTZ) due to concern about the risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis (MS).

Methods: Data from 415 patients with MS followed-up for six years after starting NTZ were collected from seven tertiary MS centers. The risk of disability worsening, i.e. reaching Expanded Disability Status Scale (EDSS) scores of 4.0 or 6.0, and the likelihood of experiencing a disability reduction of one EDSS point (or more), were assessed by propensity score-adjusted analyses in patients who discontinued and in those still on treatment at the end of follow-up.

Results: A total of 318 patients who received standard NTZ treatment without experiencing evidence of disability worsening in the first two years were included in the six-year follow-up analysis, with 196 (61.6%) still on treatment and 122 (38.4%) discontinuing after a median time of 3.5 years. Patients in the discontinuing group had a more than two-fold increased risk of disability worsening (p = 0.007), and a 68% decreased likelihood of experiencing disability reduction (p = 0.009) compared with the continuing group.

Conclusion: While discussing the overall risk/benefit profile of NTZ, patients should be advised that, in case of treatment discontinuation, the risk of disability worsening is one in three, and increases to one in two if the EDSS score at NTZ start is above 3.0.

Keywords: Natalizumab; disability; discontinuation; progressive multifocal leukoencephalopathy.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Female
  • Humans
  • Leukoencephalopathy, Progressive Multifocal / epidemiology*
  • Leukoencephalopathy, Progressive Multifocal / etiology
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Natalizumab / adverse effects
  • Natalizumab / therapeutic use*
  • Opportunistic Infections / epidemiology*
  • Opportunistic Infections / etiology
  • Prospective Studies
  • Risk Assessment
  • Withholding Treatment*
  • Young Adult

Substances

  • Natalizumab