Defining disability.

Mitoxantrone (MX) has been approved by the Food and Drug Administration (FDA) for the treatment of patients with worsening relapsing-remitting (RR) or secondary progressive (SP) multiple sclerosis (MS). However, indications should be refined and mitoxantrone reserved as a rescue therapy to: (1) patients in the relapsing-remitting phase with frequent and disabling exacerbations likely leading to permanent severe disability and (2) to patients in the secondary progressive phase whose disability progression rate increases by one EDSS point or more per year and who do not respond to other current therapies. An induction phase with the monthly intravenous administration of 12 mg/m(2) followed by a maintenance phase with 12 mg/m(2) every 3 months for 2 years seems the most effective and safe treatment regimen, not exceeding the maximum cumulative dose of 140 mg/m(2). Given the potent myelosuppressive activity of mitoxantrone, dosage should be carefully adapted to the body surface and hematological changes. Long-term toxicities (amenorrhoea and therapy-related leukemia) seem acceptable but a valid evaluation will need a longer follow-up in more patients. Cardiotoxicity, the major long-term toxicity, is clearly dose-dependent and is a strict treatment duration limiting factor. To reduce the risk of cardiac events, the drug should be administered by slow infusion (over 30 min). Analogs of mitoxantrone with a much lower cardiotoxicity are currently investigated in animal experimental models.

Disability Evaluation↗

PubMed2003

Prognostic factors for progression of disability in the secondary progressive phase of multiple sclerosis.

Predicting clinical outcome is one of the major and most interesting issues in MS patients. If the global evolution of disability (usually chosen levels on the Kurtzke's Disability Status Scale) has been widely studied, much less is known about the progression of disability during the secondary progressive phase of the disease. It is usually said that there is a poorer prognosis once patients enter a progressive phase, whether from onset (like in primary progressive MS) or after an initial relapsing-remitting phase. The secondary progressive phase of multiple sclerosis (MS) is the one most often associated with the development of severe and irreversible disability. Despite this fact, there is a lot of information about the initial relapsing-remitting phase in the literature, but much less about the secondary progressive one. We review here information available from the literature and from the Lyon MS database about this secondary progressive phase.

Disability Evaluation↗