Stabilization of rapidly worsening multiple sclerosis for 36 months in patients treated with interferon beta plus cyclophosphamide followed by interferon beta

J Neurol. 2004 Dec;251(12):1502-6. doi: 10.1007/s00415-004-0581-2.


Cyclophosphamide (CTX) is an alkylating agent related to nitrogen mustards whose anti-inflammatory and immunosuppressive effects have been utilised to treat selected cases of multiple sclerosis with a progressive and worsening course. To halt the progression of disease in patients refractory to disease modifying drugs CTX has been given, and several open-label studies have recently shown clinical benefits. In a previous study we demonstrated the effectiveness of a combination of IV monthly pulses of CTX and interferon beta (IFN-beta) in 10 patients with "rapidly transitional" form of multiple sclerosis characterised by severe and frequent attacks and rapid progression of disability. The present study reports the clinical and MRI follow-up 36 months after the discontinuation of CTX showing the maintenance of the results obtained in relapse rate (p<0.001), EDSS (p<0.001), T2 MRI total lesion load (p<0.001) and T2 lesions number (p<0.001) compared to the pre-treatment period. These encouraging findings and the absence of significant recorded side effects affirm that the association of CTX plus interferon-beta is amenable, safe and can be recommended in rapidly worsening MS patients.

Publication types

  • Clinical Trial

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Adult
  • Cyclophosphamide / therapeutic use*
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Interferon-beta / therapeutic use*
  • Magnetic Resonance Imaging
  • Male
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / physiopathology*
  • Severity of Illness Index
  • Time Factors


  • Adjuvants, Immunologic
  • Immunosuppressive Agents
  • Interferon-beta
  • Cyclophosphamide