• Time to confirmed progression of at least one EDSS point during the 3 years of the study.
  

• - percentage of patients with confirmed progression of at least one point EDSS (confirmed at 3 and 6 months) during the 3 years of the study,
  
• - annual rate of relapse;
  
• - percentage of relapse-free patients during the study period,
  
• - quality of life,
  
• - percentage of patients without evidence of disease activity on serial MRIs at months 9, 24 and 36 (number of contrast-enhanced lesions on the annual MRIs, change in lesion burden).
  

Inclusion Criteria:

• age : 18-45 years,
• Clinical disease satisfying the Poser criteria (Amdmt n°4)
• relapsing-remitting disease (Amdmt N°4)
• at least 2 exacerbations within the preceding 12 months, having left sequelae,
• MRI activity at inclusion expressed by at least one gadolinium-enhanced lesion (cranial MRI with 0.1mmol/kg gadolinium),
• a significant disability at inclusion: EDSS score between 2.5 and 5.5 (Amdt N° 4)
• written informed consent

Exclusion Criteria:

• pregnancy and breast-feeding
• use of an insufficiency effective contraceptive method,
• general immunosuppressive therapy using cyclophosphamide, mitoxantrone,or total lymphoid irradiation
• treatment with azathioprine during the 3 months preceding the study
• clinical relapse or intensive corticosteroid treatment within the 30 days preceding inclusion,
• associated disease (psychiatric disorder, depressive statenot controlled by appropriate drug therapy, history of heart disease at inclusion examination