Evidence for the efficacy of interferon beta-1b in delaying the onset of clinically definite multiple sclerosis in individuals with clinically isolated syndrome

Abstract

The BEtaferon®/BEtaseron® in Newly Emerging MS For Initial Treatment (BENEFIT) trial assessed the efficacy of early versus delayed treatment with interferon beta-1b for patients with clinically isolated syndrome (CIS). Patients were randomly assigned to receive either interferon beta-1b 250 μg every other day (early treatment, n = 292) or placebo (delayed treatment, n = 176) for 2 years or until progression to clinically definite multiple sclerosis. Clinical and magnetic resonance imaging (MRI) outcomes were assessed after 2 years (at the end of the placebo-controlled phase) and then again at 3, 5, and 8 years post randomization. MRI assessments were made after 2, 3, and 5 years. The results showed a consistent advantage of early treatment across most clinical and MRI variables, although median Expanded Disability Status Scale scores remained consistently low, with no differences between groups. These findings suggest that early treatment with interferon beta-1b improves long-term outcomes for patients presenting with CIS.

Keywords: clinically isolated syndrome; early treatment; interferon beta-1b; multiple sclerosis.

Figure 1.

Design of the BENEFIT trial. At the start of the 2-year placebo-controlled phase, patients were assigned to either interferon beta-1b (early treatment) or placebo (delayed treatment). After 2 years or progression to CDMS, patients were given the option of continuing on interferon beta-1b, switching to a different DMT, or taking no DMT [Edan et al. 2013; Kappos et al. 2006, 2007, 2009]. BENEFIT, BEtaferon®/BEtaseron® in Newly Emerging MS For Initial Treatment; CDMS, clinically definite multiple sclerosis; CIS, clinically isolated syndrome; DMT, disease-modifying therapy; MRI, magnetic resonance imaging.

Figure 2.

Hazard ratios for conversion to CDMS. Hazard ratios for conversion to CDMS favored early treatment with interferon beta-1b at all analysis intervals [Edan et al. 2013; Kappos et al. 2006, 2007, 2009]. CDMS, clinically definite multiple sclerosis; CI, confidence interval; HR, hazard ratio

Figure 3.

ARR across the 8 years of the BENEFIT study. ARR by year in patients who completed the 8-year analysis of the BENEFIT trial [Edan et al. 2013]. Overall, ARR was significantly lower in the early treatment group, which appears to be driven by differences in the first year of the study. However, the significant difference was maintained when aggregated relapse rates from years 3–8 were analyzed separately. Reproduced from Edan et al. [2013] © 2013 with permission from the BMJ Publishing Group Ltd. ^aWald-type chi-square. ARR, annualized relapse rate; BENEFIT, BEtaferon®/BEtaseron® in Newly Emerging MS For Initial Treatment; CI, confidence interval.