title: Natalizumab reduces relapse clinical severity and improves relapse recovery in MS.
abstract: OBJECTIVE
  Compare relapse clinical severity, post-relapse residual disability, and the probability of confirmed complete recovery from relapse between patients who relapsed during natalizumab (n=183/627 [29%]) and placebo (n=176/315 [56%]) treatments in the AFFIRM trial.
  
  
  METHODS
  In this post-hoc analysis, relapse clinical severity and residual disability were defined by change in Expanded Disability Status Scale (EDSS) score occurring between pre-relapse and at-relapse assessment and between pre-relapse and post-relapse assessment, respectively. Patients were considered completely recovered from relapse when their post-relapse EDSS score was less than or equal to their pre-relapse EDSS score, and this was maintained for 12 or 24 weeks.
  
  
  RESULTS
  At relapse, an increase in EDSS score of ≥0.5 points occurred in 71% of natalizumab and 84% of placebo patients (P=0.0088); an increase of ≥1.0 point occurred in 49% of natalizumab and 61% of placebo patients (P=0.0349) (mean increase in EDSS at relapse: natalizumab=0.77; placebo=1.09; P=0.0044). After relapse, residual disability of ≥0.5 EDSS points remained in 31% of natalizumab and 45% of placebo patients (P=0.0136) (mean post-relapse residual EDSS increase: natalizumab=0.06; placebo=0.28; P=0.0170). In patients with an increase in EDSS of ≥0.5 or ≥1.0 during relapse, natalizumab increased the probability of 12-week confirmed complete recovery from relapse by 55% (hazard ratio [HR]=1.554; P=0.0161) and 67% (HR=1.673; P=0.0319) compared to placebo, respectively.
  
  
  CONCLUSIONS
  In AFFIRM, natalizumab treatment decreased the clinical severity of relapses and improved recovery from disability induced by relapses. These beneficial effects would limit the step-wise accumulation of disability.
authors.affiliation: Icahn School of Medicine at Mount Sinai, The Corinne Goldsmith Dickinson Center for MS, 5 E. 98th Street, Box 113B, New York, NY, USA. Electronic address: fred.lublin@mssm.edu.
authors.forename: Fred D
authors.initials: FD
authors.lastname: Lublin
authors.affiliation: University of Alabama at Birmingham, AL, USA. Electronic address: cutterg@uab.edu.
authors.forename: Gary
authors.initials: G
authors.lastname: Cutter
authors.affiliation: Barts and the London School of Medicine and Dentistry, London, United Kingdom. Electronic address: g.giovannoni@qmul.ac.uk.
authors.forename: Gavin
authors.initials: G
authors.lastname: Giovannoni
authors.affiliation: Biogen Idec Inc., Cambridge, MA, USA. Electronic address: amy.pace@biogenidec.com.
authors.forename: Amy
authors.initials: A
authors.lastname: Pace
authors.affiliation: Biogen Idec Inc., Cambridge, MA, USA. Electronic address: nolan.campbell@biogenidec.com.
authors.forename: Nolan R
authors.initials: NR
authors.lastname: Campbell
authors.affiliation: Biogen Idec Inc., Cambridge, MA, USA. Electronic address: shibeshih.belachew@biogenidec.com.
authors.forename: Shibeshih
authors.initials: S
authors.lastname: Belachew
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000503:physiopathology; D015999:Multivariate Analysis; D000069442:Natalizumab; D011336:Probability; D012008:Recurrence; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D000069442:Natalizumab
keywords: Disability; Natalizumab; Placebo; Recovery; Relapse; Severity