Treatment strategies for multiple sclerosis: When to start, when to change, when to stop?

Abstract

Multiple sclerosis (MS) is a chronic inflammatory condition of the central nervous system determined by a presumed autoimmune process mainly directed against myelin components but also involving axons and neurons. Acute demyelination shows as clinical relapses that may fully or partially resolve, while chronic demyelination and neuroaxonal injury lead to persistent and irreversible neurological symptoms, often progressing over time. Currently approved disease-modifying therapies are immunomodulatory or immunosuppressive drugs that significantly although variably reduce the frequency of attacks of the relapsing forms of the disease. However, they have limited efficacy in preventing the transition to the progressive phase of MS and are of no benefit after it has started. It is therefore likely that the potential advantage of a given treatment is condensed in a relatively limited window of opportunity for each patient, depending on individual characteristics and disease stage, most frequently but not necessarily in the early phase of the disease. In addition, a sizable proportion of patients with MS may have a very mild clinical course not requiring a disease-modifying therapy. Finally, individual response to existing therapies for MS varies significantly across subjects and the risk of serious adverse events remains an issue, particularly for the newest agents. The present review is aimed at critically describing current treatment strategies for MS with a particular focus on the decision of starting, switching and stopping commercially available immunomodulatory and immunosuppressive therapies.

Keywords: Multiple sclerosis, Disease-modifying therapy, Treatment start, Treatment switch, Treatment stop, Interferon beta, Glatiramer acetate, Azathioprine, Natalizumab, Fingolimod

Core tip: Disease-modifying therapies for multiple sclerosis (MS) modulate or suppress with different mechanisms the autoimmune process that underlies the disease. Patients with relapsing MS may benefit from treatment but individual response to a given therapy and adverse events occurrence are largely unpredictable and many cases need to change several drugs to stabilize their disease. Nevertheless, a high proportion of patients evolve to a progressive phase, which is not responsive to any existing therapy. As opposed, some cases have a benign course without treatment. A critical review of strategies for starting, switching and stopping disease-modifying therapies for MS is here presented.