Treatment of relapsing-remitting multiple sclerosis with high-dose cyclophosphamide induction followed by glatiramer acetate maintenance

Daniel M. Harrison, Douglas E. Gladstone, Edward Hammond, Jeffrey Cheng, Richard J. Jones, Robert A. Brodsky, Douglas Kerr, Justin C. McArthur, Adam Kaplin

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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.

Original languageEnglish (US)
Pages (from-to)202-209
Number of pages8
JournalMultiple Sclerosis Journal
Issue number2
StatePublished - Feb 2012


  • cyclophosphamide
  • glatiramer acetate
  • immunosuppression
  • multiple sclerosis

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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