Our review should provide some guidance to clinicians and patients. On the basis of high quality evidence, natalizumab and IFNß-1a (Rebif) are superior to all other treatments for preventing clinical relapses in RRMS in the short-term (24 months) compared to placebo. Moderate quality evidence supports a protective effect of natalizumab and IFNß-1a (Rebif) against disability progression in RRMS in the short-term compared to placebo. These treatments are associated with long-term serious adverse events and their benefit-risk balance might be unfavourable. IFNß-1b (Betaseron) and mitoxantrone probably decreased the odds of the participants with RRMS having relapses, compared with placebo (moderate quality of evidence). The benefit-risk balance with azathioprine is uncertain, however this agent might be effective in decreasing the odds of the participants with RRMS having relapses and disability progression over 24 to 36 months, compared with placebo. The lack of convincing efficacy data shows that IFNß-1a (Avonex), intravenous immunoglobulins, cyclophosphamide and long-term steroids have an unfavourable benefit-risk balance in RRMS. None of the included treatments are effective in decreasing disability progression in patients with progressive MS. It is important to consider that the clinical effects of all these treatments beyond two years are uncertain, a relevant point for a disease of 30 to 40 years duration. Direct head-to-head comparison(s) between natalizumab and IFNß-1a (Rebif) or between azathioprine and IFNß-1a (Rebif) should be top priority on the research agenda and follow-up of the trial cohorts should be mandatory.
Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria.
To evaluate the efficiency of mitoxantrone in multiple sclerosis.
                Forty two patients with confirmed multiple sclerosis, selected as having a very active disease on clinical and MRI criteria were randomised to receive either mitoxantrone (20 mg intravenously (IV) monthly) and methylprednisolone (1 g iv monthly) or methylprednisolone alone over six months. In the steroid alone group five patients dropped out due to severe exacerbation.
                Blinded analysis of MRI data showed significantly more patients with no new enhancing lesions in the mitoxantrone group compared with the steroid alone group, (90% v 31%, P < 0.001). In the mitoxantrone group there was a month by month decrease almost to zero in the number of new enhancing lesions, and in the total number of enhancing lesions, whereas both remained high in the steroid alone group. The differences were significant for both indices at all months from 1-6. Unblinded clinical assessments showed a significant improvement in change in EDSS at months 2-6 in the mitoxantrone group, with a final mean improvement of more than one point (-1.1 v + 0.3; P < 0.001). There was a significant reduction in the number of relapses (7 v 31; P < 0.01), and an increase in the number of patients free of exacerbation (14 v 7; P < 0.05).
                In this selected group of patients with multiple sclerosis with very active disease, mitoxantrone combined with methylprednisolone was effective in improving both clinical and MRI indices of disease activity over a period of six months whereas methylprednisolone alone was not. Further double blinded long term studies are needed to properly evaluate the effect of mitoxantrone on progression in disability.