Mitoxantrone prior to interferon beta-1b in aggressive relapsing multiple sclerosis: a 3-year randomised trial.

Abstract

OBJECTIVES:

The long-term impact of interferon-beta-1b (IFN) might be improved by short-term immunosuppression with mitoxantrone (MITOX) in aggressive relapsing-remitting multiple sclerosis (ARMS) patients.

METHODS:

In this 3-year clinical and MRI study, 109 ARMS patients (two or more relapses in the previous 12 months and one or more gadolinium (Gd)-enhancing MRI lesion) were randomised into two groups: 54 patients received MITOX monthly (12 mg/m(2); maximum 20 mg) combined with 1 g of methylprednisolone (MP) for 6 months followed by IFN for the last 27 months, and 55 patients received IFN for 3 years combined with 1 g of MP monthly for the first 6 months. The primary endpoint was the time to worsen by at least one Expanded Disability Status Scale point confirmed at 3 months.

RESULTS:

The time to worsen by at least one Expanded Disability Status Scale point confirmed at 3 months was delayed by 18 months in the MITOX group compared with the IFN group (p<0.012). The 3-year risk of worsening disability was reduced by 65% in the MITOX group relative to the IFN group (11.8% vs 33.6%). MITOX patients had a reduced relapse rate by 61.7%, a reduced number of Gd-enhancing lesions at month 9 and a slower accumulation of new T2 lesions at each time point.

CONCLUSIONS:

Although there were limitations in this investigator-academic-driven study, the data do suggest that mitoxantrone induction therapy prior to INF beta-1b may have a role in aggressive disease.

• Authors: G Edan, G Comi, E Le Page, E Leray, M A Rocca, M Filippi, French–Italian Mitoxantrone Interferon-beta-1b Trial Group
• Journal: Journal of neurology, neurosurgery, and psychiatry (J Neurol Neurosurg Psychiatry) Vol. 82 Issue 12 Pg. 1344-50 (Dec 2011) ISSN: 1468-330X [Electronic] England
• PMID: 21436229 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Immunologic Factors
• Immunosuppressive Agents
• Interferon beta-1b
• Interferon-beta
• Gadolinium
• Mitoxantrone
• Methylprednisolone

Topics

• Adult
• Brain (drug effects, pathology)
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Gadolinium
• Humans
• Immunologic Factors (administration & dosage, therapeutic use)
• Immunosuppressive Agents (administration & dosage, therapeutic use)
• Interferon beta-1b
• Interferon-beta (administration & dosage, therapeutic use)
• Magnetic Resonance Imaging (methods)
• Male
• Methylprednisolone (administration & dosage, therapeutic use)
• Mitoxantrone (administration & dosage, therapeutic use)
• Multiple Sclerosis, Relapsing-Remitting (drug therapy, pathology)
• Neuroimaging (methods)
• Severity of Illness Index