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-beta).

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-beta, 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-beta-1a (30 microg IM once weekly and 22 microg SC once weekly) and 1 involving IFN-beta-1b (250 microg SC qod). In these trials, treatment with IFN-beta 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-beta effectively reduced the risk of developing clinically definite MS in CIS patients with a first demyelinating event and positive brain MRI.