title: Treatment of relapsing-remitting multiple sclerosis with high-dose cyclophosphamide induction followed by glatiramer acetate maintenance.
abstract: BACKGROUND
  Previous studies have described stabilization of aggressive multiple sclerosis (MS) with one-time induction therapy with high-dose cyclophosphamide (HiCy). The long-term benefit of this stabilization followed by conventional therapy has not been explored.
  
  
  OBJECTIVE
  The objective of this study was to evaluate the safety and clinical outcomes following treatment of relapsing-remitting MS with HiCy induction therapy followed by glatiramer acetate maintenance.
  
  
  METHODS
  A retrospective review of a closely followed population of thirty two MS patients treated with HiCy (200mg/kg intravenous infusion over 4 days) followed by maintenance with glatiramer acetate was performed.
  
  
  RESULTS
  Annualized relapse rate was reduced from 1.37 in the 2 years prior to treatment to 0.27 over a mean post-treatment follow-up period of 14 months (range 0.5-33.8). The projected probability of relapse-free survival at 2 years was 0.64 (95% CI 0.37-0.82). The projected probability of Expanded Disability Status Scale (EDSS) progression-free survival at 2 years was 0.77 (95% CI 0.43-0.92). The mean number of gadolinium-enhanced lesions was reduced from 0.86 (SD 1.6) at baseline to 0 at 12 months and 0.08 (SD 0.28) at 15-24 months. A total of 55% of patients had no evidence of disease activity in follow-up. Infectious complications occurred in 47% with no long-term morbidity and no deaths.
  
  
  CONCLUSIONS
  Induction therapy with HiCy followed by long-term maintenance with glatiramer acetate is well tolerated in patients with MS, and appears to be efficacious in reducing the risk of relapse, disability progression, and new MRI lesions.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. dharri90@jhmi.edu
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Harrison
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Gladstone
authors.forename: Edward
authors.initials: E
authors.lastname: Hammond
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cheng
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Jones
authors.forename: Robert A
authors.initials: RA
authors.lastname: Brodsky
authors.forename: Douglas
authors.initials: D
authors.lastname: Kerr
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
authors.forename: Adam
authors.initials: A
authors.lastname: Kaplin
mesh_terms: D000328:Adult; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D012189:Retrospective Studies; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate; D003520:Cyclophosphamide