Shifting the paradigm toward earlier treatment of multiple sclerosis with interferon beta

Background: Axonal damage occurs early in the course of multiple sclerosis (MS). Among untreated patients, 85% to 94% with a first clinically isolated syndrome (CIS) suggestive of MS and positive findings on magnetic resonance imaging (MRI) are at risk for developing MS. Objectives: This article reviews the current literature concerning early diagnosis of MS, the rationale for early immunomodulatory treatment of patients with a CIS and MRI evidence of central nervous system lesions, and the efficacy of early treatment with interferon beta (IFN-β). Methods: MEDLINE was searched from 1990 through the end of 2008 for papers published in English concerning the treatment of MS. Search terms included IFN-β, early treatment, CIS, and multiple sclerosis, and limits were set to return results related to human clinical trials in adults. Results: Three pivotal randomized controlled trials were identified, 2 involving IFN-β-1a (30 μg IM once weekly and 22 μg SC once weekly) and 1 involving IFN-β-1b (250 μg SC qod). In these trials, treatment with IFN-β effectively reduced the risk of developing MS by up to 50% in patients with a CIS. Furthermore, compared with delayed treatment, early treatment was associated with a reduced risk of disease progression: a 40% reduction in risk for confirmed disability progression at 3 years and a 41% reduction in risk of MS at 3 years. Conclusions: The evidence that axonal damage begins in the early stages of MS, before symptoms are evident, provides a rationale for early intervention with immunomodulatory agents. In 3 pivotal clinical trials, IFN-β effectively reduced the risk of developing clinically definite MS in CIS patients with a first demyelinating event and positive brain MRI.