Long-term experience with current disease-modifying drugs in multiple sclerosis

Abstract

Five different immunomodulatory treatments have been developed and approved for the treatment of multiple sclerosis. These have been shown to be efficacious over the short-term in the reduction of relapse rates, measures of disease activity and disease progression in randomised, placebo-controlled trials. However, multiple sclerosis is a chronic progressive disease of variable course in which long-term benefits of treatment are critically important. It is not possible to obtain data on long-term outcome from placebo-controlled trials and observational open-label designs are required. Ideally, these would involve prospective follow-up of all included patients over decades. Long-term studies with β-interferons have generally used retrospective designs which have important limitations in terms of case ascertainment and selection bias. Nonetheless, they suggest that treatment benefit may be maintained over time. Glatiramer acetate is the only immunomodulatory treatment which has been studied prospectively over a period of ten years, and for which outcomes have been compared between subjects with continuous treatment and those in whom glatiramer acetate was discontinued. Ten-year data showed suppression of relapse rate to be maintained with 62% showing stable or improved disability levels. Disability progression was less than what would be expected from natural history studies of untreated patients with multiple sclerosis.