title: The clinical meaning of walking speed as measured by the timed 25-foot walk in patients with multiple sclerosis.
abstract: OBJECTIVE
  Walking impairment, a common clinical manifestation of multiple sclerosis (MS), is often measured in clinical practice and clinical trials using the Timed 25-Foot Walk (T25-FW).
  
  
  OBJECTIVE
  To evaluate the relationship between walking speed measured by the T25-FW and the Physical Component Summary (PCS) score of the 36-Item Short Form Health Survey (SF-36) to better understand the clinical meaning of T25-FW walking speed in MS.
  
  
  METHODS
  We retrospectively analyzed data from 3 clinical trials (Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis [AFFIRM], Safety and Efficacy of Natalizumab in Combination With Interferon Beta-1a in Patients With Relapsing-Remitting Multiple Sclerosis [SENTINEL], and International MS Secondary Progressive Avonex Controlled Trial [IMPACT]) that included T25-FW and SF-36 scores as outcomes in patients with MS. Patients had secondary-progressive MS and an Expanded Disability Status Scale score of 3.5 to 6.5 or relapsing-remitting MS and an Expanded Disability Status Scale score of 0 to 5.0.
  
  
  METHODS
  We used Spearman rank correlation and Pearson product moment correlation (r ) and descriptive statistics to evaluate retrospectively the relationship between the SF-36 PCS score and T25-FW walking speed at baseline and the 2-year changes from baseline.
  
  
  RESULTS
  Among all 2549 patients from the 3 trials, walking speed and SF-36 PCS score at baseline were significantly correlated (n = 2333; r = 0.48; P < .001). In placebo-treated patients at 2 years, the percentage of change from baseline in walking speed was significantly correlated with the change from baseline in SF-36 PCS score (r = 0.35; P < .001). Significant correlations between the change in SF-36 PCS scores and the percentage of change in walking speed at 2 years also were observed in groups receiving active treatment (r, 0.13-0.28; P ≤ .005). Among placebo-treated patients, 27.5% had a clinically meaningful worsening (≥ 5-point decrease) in SF-36 PCS scores during the 2 years. Walking speed declined by 21.8% in these patients after 2 years, but only by 5.4% in those without worsening of SF-36 PCS scores.
  
  
  CONCLUSIONS
  In patients with MS, walking speed measured using the T25-FW correlated with SF-36 PCS scores such that a decline in walking speed of 20% to 25% corresponded to a clinically meaningful worsening of SF-36 PCS scores. A 20% to 25% decline in walking speed may be a clinically meaningful threshold for defining worsening using the T25-FW in MS clinical trials and for monitoring patients in clinical settings.
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Cohen
authors.affiliation: Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Arun V
authors.initials: AV
authors.lastname: Krishnan
authors.affiliation: Department of Neurology, University of Rochester Medical Center, Rochester, New York.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Goodman
authors.affiliation: Biogen Idec, Weston, Massachusetts.
authors.forename: James
authors.initials: J
authors.lastname: Potts
authors.affiliation: Biogen Idec, Weston, Massachusetts.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurology, Charles University, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.affiliation: Department of Neurology, VU Medical Center, Amsterdam, the Netherlands.
authors.forename: Chris
authors.initials: C
authors.lastname: Polman
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, Ohio7currently with Biogen Idec, Weston, Massachusetts.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rudick
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*; D000069442:Natalizumab; D011788:Quality of Life; D012189:Retrospective Studies; D013647:Task Performance and Analysis; D016138:Walking; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab; D016899:Interferon-beta; D000068556:Interferon beta-1a