title: Alemtuzumab improves neurological functional systems in treatment-naive relapsing-remitting multiple sclerosis patients.
abstract: BACKGROUND
  Individual functional system scores (FSS) of the Expanded Disability Status Scale (EDSS) play a central role in determining the overall EDSS score in patients with early-stage multiple sclerosis (MS). Alemtuzumab treatment improves preexisting disability for many patients; however, it is unknown whether improvement is specific to certain functional systems.
  
  
  OBJECTIVE
  We assessed the effect of alemtuzumab on individual FSS of the EDSS.
  
  
  METHODS
  CAMMS223 was a 36-month, rater-blinded, phase 2 trial; treatment-naive patients with active relapsing-remitting MS, EDSS ≤3, and symptom onset within 3 years were randomized to annual courses of alemtuzumab or subcutaneous interferon beta-1a (SC IFNB-1a) 44 μg three times weekly.
  
  
  RESULTS
  Alemtuzumab-treated patients had improved outcomes versus SC IFNB-1a patients on most FSS at Month 36; the greatest effect occurred for sensory, pyramidal, and cerebellar FSS. Among patients who experienced 6-month sustained accumulation of disability, clinical worsening occurred most frequently in the brainstem and sensory systems. For patients with 6-month sustained reduction in preexisting disability, pyramidal and sensory systems contributed most frequently to clinical improvement.
  
  
  CONCLUSIONS
  Alemtuzumab demonstrated a broad treatment effect in improving preexisting disability. These findings may influence treatment decisions in patients with early, active relapsing-remitting MS displaying neurological deficits. ClinicalTrials.gov Identifier NCT00050778.
authors.affiliation: Central Texas Neurology Consultants, MS Clinic of Central Texas, Round Rock, TX, USA. Electronic address: foxtexms@gmail.com.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Fox
authors.affiliation: Consultants in Neurology MS Center, Northbrook, IL, USA. Electronic address: dwynnmd@gmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wynn
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. Electronic address: ajc1020@medschl.cam.ac.uk.
authors.forename: Alasdair J
authors.initials: AJ
authors.lastname: Coles
authors.affiliation: Sanofi Genzyme, Cambridge, MA, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Palmer
authors.affiliation: Sanofi Genzyme, Cambridge, MA, USA. Electronic address: david.margolin@genzyme.com.
authors.forename: David H
authors.initials: DH
authors.lastname: Margolin
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000188:drug therapy*; D009422:Nervous System Diseases / Q000175:diagnosis / Q000188:drug therapy; D016037:Single-Blind Method
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074323:Alemtuzumab
keywords: Alemtuzumab; Disability; Disease-modifying therapy; Expanded Disability Status Scale; Functional systems; Multiple sclerosis