Natalizumab improves ambulation in relapsing-remitting multiple sclerosis: results from the prospective TIMER study and a retrospective analysis of AFFIRM

Eur J Neurol. 2015 Mar;22(3):570-7. doi: 10.1111/ene.12618. Epub 2014 Dec 15.

Abstract

Background and purpose: Impaired ambulation is a prominent disabling symptom of multiple sclerosis and can lead to reduced quality of life. Whether natalizumab, a monoclonal antibody shown to reduce disease activity in relapsing-remitting multiple sclerosis, could impact ambulation performance was examined.

Methods: A prospective open-label study, TIMER, was conducted in natalizumab-naive patients (n = 215). The timed 25-foot walk (T25FW) and timed 100-m walk (T100MW) were assessed at baseline and at weeks 24 and 48 of natalizumab therapy, together with Expanded Disability Status Scale scores. The effects of natalizumab on T25FW performance were also examined in a retrospective analysis of natalizumab-treated patients (n = 627) and placebo control patients (n = 315) from the AFFIRM study.

Results: In TIMER, a significant increase from baseline in T25FW speed was seen at week 24 (P = 0.0074) and in T100MW speed at weeks 24 and 48 (both P < 0.001). A greater proportion of patients showed clinically meaningful increases (≥20%) in walking speed on the T100MW (25%) than on the T25FW (13%) at week 48 (P = 0.032). In AFFIRM, natalizumab increased the proportion of patients with ≥20% confirmed improvement in T25FW speed at year 2 by 78% versus placebo (P = 0.0133).

Conclusions: Natalizumab increased walking speed in patients with relapsing-remitting multiple sclerosis. The T100MW may be more sensitive to changes in ambulation capacity than the T25FW, and both tests appear to detect clinically meaningful improvements in ambulatory function.

Keywords: Expanded Disability Status Scale; ambulation; natalizumab; quality of life; relapsing−remitting multiple sclerosis; timed 100-meter walk; timed 25-foot walk; walking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Exercise Test
  • Female
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / pharmacology*
  • Male
  • Middle Aged
  • Mobility Limitation
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Natalizumab / administration & dosage
  • Natalizumab / pharmacology*
  • Outcome Assessment, Health Care*
  • Prospective Studies
  • Retrospective Studies
  • Severity of Illness Index
  • Walking / physiology*

Substances

  • Immunologic Factors
  • Natalizumab