The aim of the study is to determine whether a therapeutic strategy combining mitoxantrone and interferon beta1b can delay disease progression of at least one point on EDSS scale in patients with clinically very active relapsing-remitting multiple sclerosis.

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