The effects of intramuscular interferon beta-Ia in patients at high risk for development of multiple sclerosis: A post hoc analysis of data from CHAMPS

Abstract

Background: In the Controlled High Risk Subjects Avonex® Multiple Sclerosis Prevention Study (CHAMPS), intramuscular (IM) interferon beta-1a (IFNβ-1a) delayed the development of clinically definite multiple sclerosis (CDMS) in patients with a single demyelinating event who had magnetic resonance imaging (MRI) evidence of previous subclinical disease activity (defined as ≥2 T2-weighted hyperintense lesions, 1 of which was periventricular or ovoid, on unenhanced MRI scans). Objective: This post hoc analysis was conducted to assess the effects of IM IFNβ-1a on delaying the development of CDMS in a subgroup of CHAMPS patients who met a more stringent definition of high risk than was used in that trial. Methods: Patients from the overall CHAMPS population were included in the present analysis if they had ≥9 T2-weighted hyperintense lesions and ≥1 gadolinium-enhanced lesion on the baseline MRI scan. The cumulative probability of developing CDMS in each treatment group was calculated using the Kaplan-Meier product-limit method and compared using the log-rank test. The actual proportions of patients who developed CDMS in each treatment group were calculated and compared using the chi-square test. Results: Ninety-one patients met the more stringent definition of high risk and were included in the subgroup analysis. Fifty-one patients (56.0%) received IFNβ-1a 30 μg IM once weekly and 40 (44.0%) received placebo. Baseline demographic and clinical characteristics were similar between the 2 groups. Seventy-four patients (81.3%) were female, 80 (87.9%) were white, and the mean age was 33.0 years. Overall, IM IFNβ-1a reduced the rate of development of CDMS by 66% compared with the placebo group ( P = 0.002, log-rank test) over the 3-year follow-up period. At 2 years, the Kaplan-Meier estimate of the cumulative probability of developing CDMS was 21% in the IM IFNβ-1a group and 56% in the placebo group, representing a 63% reduction in risk for CDMS with IFNβ-1a ( P = 0.002, log-rank test). The results based on the actual proportions of patients developing CDMS were similar to the Kaplan-Meier estimates. Conclusions: The results of this subgroup analysis are compatible with IM IFNβ-1a reducing the risk of a second demyelinating event in patients meeting the more stringent definition of high risk. Although the treatment effect of IFNβ-1a was significant in both the overall CHAMPS population (44% risk reduction vs placebo; P = 0.002) and in this high-risk subgroup (66%), the results of the present analysis suggest that the magnitude of treatment benefit with IFNβ-1a may be greater in patients with more disease activity, as measured by MRI parameters.