OBJECTIVE: To evaluate the efficacy of mitoxantrone (MTX) on clinical and neuroradiological parameters of patients who had a relapse of neuromyelitis optica spectrum (NMOS) within the 12 previous months.
METHODS: MTX (12 mg/m(2)) combined with methylprednisolone 1 g as three monthly courses followed by three quarterly courses was administered during an observational multicentre open study including 51 consecutive patients (28 NMO, 23 limited forms of NMO) of the French Caribbean and Guyana. The main outcome measure was the reduction of the annualised relapse rate (ARR), and the secondary outcome measures were alteration of disability measured by expanded disability status scale (EDSS) score, the time to onset of the first relapse, and the progression of neuroradiological lesions at 1 year of treatment.
RESULTS: At 1 year of treatment, the ARR dropped from 1.82 to 0.37 (p<0.0001). The mean EDSS score improved by 1.3 points, going from 5.8 at baseline to 4.5 at 1 year (p<0.0001). The number of patients showing gadolinium (Gad)+ spinal cord lesions at baseline, that is, 46.9%, dropped to 10.6% (a 77.4% reduction; p=0.02). The median time to onset of the first relapse was 18 months. IgG-NMO seropositivity was a predictive factor of relapse (p=0.006). A case of acute myeloid leukaemia was observed after a mean time span of 4.8 years.
CONCLUSIONS: In this observational NMO study, MTX decreased dramatically the frequency of relapses, which is directly related to progression of disability or even death in this disorder.
NMO, used to be called Devics MS, is characterised by spinal cord and optic nerve demyelination, although brains are modestly affected also. This is associated with the development of self-reactive antibodies. Mitoxantrone is an anti-cancer drug that kills dividing cells including T cells and so has a prediliction to attack B cells, which have an intrinsic relatively quick turn over rate. This has a dramatic effect on relapse rate and removing relapses is a good thing and removes some of the influences causing disability. We were among st the first to show it inhibits attacks in EAE many years ago and it inhibits relapses in MS. The down side is it has cardiotoxic effects which limits the amount of time you can take the drug and there is also high increased cancer risk. But again tells us that having relapses is not good this is the case for both NMO and MS.