Assessing long-term effects of disease-modifying drugs

Multiple sclerosis is an immune-mediated disease of the central nervous system. The pathological picture is characterised by inflammation and axonal damage which are present from the earliest stages. Initially closely associated, neurodegeneration appears to evolve independently of inflammation later in the course of the disease. It is commonly believed that accumulating axonal loss is responsible for irreversible neurological disability. The treatment goal for disease-modifying treatments in multiple sclerosis is to prevent axonal damage and irreversible disability. Therefore, therapy should be initiated as early as possible in the disease process in order to modulate inflammation and minimise axonal loss. Four disease modifying treatments (DMTs) are currently available, namely three β-interferon preparations and glatiramer acetate. Studies using MRI surrogate markers suggest that β-interferons may be partially effective in preventing brain atrophy and that glatiramer acetate may slow brain atrophy and attenuate axonal loss. Looking at clinical measures, all DMTs provide a moderate reduction (around 30 %) in relapse rate in the short-term. In order to judge their long-term benefit, these treatments need to be assessed in well-designed observational studies.