Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome

Abstract

We designed a randomized, placebo-controlled, multicentre trial involving 51 relapsing-remitting multiple sclerosis patients to determine the clinical efficacy of mitoxantrone treatment over 2 years. Patients were allocated either to the mitoxantrone group (27 patients receiving I.V. infusion of mitoxantrone every month for 1 year at the dosage of 8 mg/m2) or to the placebo group (24 patients, receiving I.V. infusion of saline every month for 1 year) using a centralized randomization system. Disability at entry and at 12-24 months was evaluated by four blinded neurologists trained in the application of the Kurtzke Expanded Disability Scale (EDSS). In addition, the number and clinical characteristics of the exacerbations over the 24 months were recorded by the local investigators. MRI, at 0, 12 and 24 months, was performed with a 0.2 T permanent unit. MRI data were analysed by two blinded neuroradiologists. All patients underwent a clinical evaluation. A statistically significant difference in the mean number of exacerbations was observed between the mitoxantrone group and placebo group both during the 1st and the 2nd year. Although there was no statistically significant benefit in terms of mean EDSS progression over 2 years, the proportion of patients with confirmed progression of the disease, as measured by a one point increase on the EDSS scale, was significantly reduced at the 2nd year evaluation in the mitoxantrone group. Forty-two (23 mitoxantrone, 19 placebo) patients underwent all MRI examinations during the 24-month period. We observed a trend towards a reduction in the number of new lesions on T2-weighted images in the mitoxantrone group. Our study suggests that mitoxantrone might be effective in reducing disease activity, both by decreasing the mean number of exacerbations and by slowing the clinical progression sustained by most patients after 1 year from the end of treatment.

Mitoxantrone in secondarily progressive multiple sclerosis: a series of 18 patients

“…In fact, benefit can be seen in disease progression in patients with secondary progressive MS (SPMS) 1 3 -1 5 . Randomized studies has also showed reduction of relapsing and new lesions incidence using magnetic resonance imaging (MRI) [16][17][18] . Mitoxantrone (MX) acts as an immunosupressive agent which alters B and T lymphocytes responses to central nervous system (CNS) antigens, and through this process it seems to avoid axonal lesion and macrophages mediated demyelination [1][2][3][4][5][6][7][8][9]13,19 .…”

Nouveautés thérapeutiques et stratégies émergentes dans la sclérose en plaques

“…La mitoxantrone est utilisée dans la SEP comme agent immunosuppresseur. Plusieurs études ont montré qu'elle réduisait le nombre de poussées, l'apparition de nouvelles lésions rehaussées par le gadolinium (ce qui traduit une rupture de la barrière hémato-encéphalique) 1 et la progression du handicap [2][3][4]. L'efficacité de la mitoxantrone se maintient plusieurs mois après l'arrêt du traitement.…”

Immunosuppressive Agents in Multiple Sclerosis

“…2) In an Italian trial, the efficacy of mitoxantrone was assessed in 51 patients with relapsing-remitting MS. 13 The patients were randomized and received either mitoxantrone (8 mg/m 2 body surface) or a placebo. Clinical assessment was performed by blinded physicians.…”