Mitoxantrone prior to interferon beta-1b in aggressive relapsing multiple sclerosis: a 3-year randomised trial
- G Edan1,2,3,
- G Comi4,5,
- E Le Page1,2,
- E Leray2,3,
- M A Rocca5,6,
- M Filippi5,6,
- for The French–Italian Mitoxantrone Interferon-beta-1b Trial Group*
- 1Department of Neurology, University Hôpital Pontchaillou, Centre Hospitalier Universitaire, Service de Neurologie, Rennes, France
- 2Institut National de la Santé et de la Recherche Médicale, CIC 0203, Hôpital Pontchaillou, Rennes, France
- 3Université Européenne de Bretagne, Université de Rennes 1, Faculté de médecine, Rennes, France
- 4Department of Neurology, University Hospital San Raffaele, Milan, Italy
- 5Division of Neuroscience, University Vita-Salute, Institute of Experimental Neurology, Milan, Italy
- 6Neuroimaging Research Unit, University Hospital San Raffaele, Milan, Italy
- Correspondence to Professor Gilles Edan, Service de Neurologie, CHU Pontchaillou, Rennes cedex 35033, France;
- Received 10 September 2010
- Revised 23 February 2011
- Accepted 1 March 2011
- Published Online First 24 March 2011
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/m2; 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.
- Aggressive relapsing-remitting multiple sclerosis
- interferon beta-1b
- multiple sclerosis
↵* For the list of co-investigators in The French—Italian Mitoxantrone Interferon-beta-1b Trial Group see the end of the paper
Funding Supported by an academic grant (Programme Hospitalier de Recherche Clinique, from the French Health Ministry), with additional grants from industry (Bayer-Schering, Lederle and Immunex). GE has received research support and compensation as a speaker from Biogen Idec, Serono and Sanofi-Aventis, Bayer Schering Pharma AG, LFB, and has acted as a consultant for Teva Pharmaceuticals, Merck-Serono, Bayer-Schering, Biogenidec, and LFB. GC has received consulting fees from Novartis, Teva Pharmaceuticals, Sanofi-Aventis, Merck Serono and Bayer Schering, and lecture fees from Novartis, Teva Pharmaceuticals, Sanofi-Aventis, Merck Serono, Biogen-Dompe and Bayer Schering. ELP has received compensation as a speaker from Biogen Idec, Serono, Sanofi-Aventis and Bayer Schering Pharma AG. MF has received research support and compensation as a speaker from Teva Pharmaceuticals, Merck-Serono, Bayer-Schering, Biogen-Dompe and Genmab, and has acted as a consultant for Teva Pharmaceuticals, Merck-Serono, Bayer-Schering, Biogen-Dompe and Genmab.
Competing interests None.
Patient consent Obtained.
Ethics approval Ethics approval was provided by the Centre de Protection des Personnes pour la Recherche Biomédicale Centre Hospitalier Universitaire Rennes.
Provenance and peer review Not commissioned; externally peer reviewed.