Clinical and MRI Benefits of IFN ß-1a 44 µg SC tiw Treatment over 1 Year in Patients with RMS: Subgroup Analyses of the PRISMS Study

Background: In the PRISMS-2 study, interferon beta-1a (IFN β-1a) 44 and 22 µg given subcutaneously (SC) three times weekly (tiw) demonstrated significant clinical and magnetic resonance imaging (MRI) benefits versus placebo in patients with relapsing forms of multiple sclerosis (RMS).

Objectives: To characterize the early treatment effect of IFN β-1a 44 μg SC tiw at 1 year in pre-selected subgroups of patients with RMS from the PRISMS study. 

Methods: This post hoc subgroup analysis assessed the treatment effect of IFN β-1a 44 μg SC tiw versus placebo over 1 year in patient subgroups, stratified by baseline: 1) Expanded Disability Status Scale (EDSS) ≤ and >2.5 (median value); 2) relapses (prior 2 years) of < and ≥3; and 3) burden of disease (BOD; total T2 lesion area) of ≤ and > 1992.5 mm² (median value), as well as other characteristics (age, sex, and time since onset of MS). Relapse and MRI endpoints assessed included annualized relapse rate (ARR), time to first relapse, proportion of patients relapse-free, and number of active T2 lesions/patient/scan. Relative treatment effects of IFN β-1a 44 μg SC tiw versus placebo were examined using rate ratios, hazard ratios, and odds ratios.

Results: In PRISMS-2, patients were randomized to IFN β-1a 44 µg (n=184) or 22 µg (n=189) SC tiw, or placebo (n=187). In all subgroups examined, point estimates and 95% confidence intervals indicated IFN β-1a 44 μg SC tiw reduced ARR versus placebo, consistent with the overall population; rate ratios ranged from 0.46 (0.32–0.66) among patients with <4 years since MS onset (n=149) to 0.71 (0.55–0.92) among patients with baseline EDSS ≤2.5 (n=221). All estimates of relative treatment effects favored IFN β-1a 44 μg SC tiw over placebo on additional relapse endpoints in all baseline EDSS, relapse, and BOD subgroups investigated at 1 year. In analysis of active T2 lesions, rate ratios favored IFN β-1a 44 μg SC tiw over placebo in all subgroups examined, ranging from 0.22 (0.14–0.33) in patients with <4 years since MS onset (n=147) to 0.38 (0.27–0.53) in patients with ≥4 years since MS onset (n=219).

Conclusions: Subgroup analyses were consistent with findings in the overall population, demonstrating the treatment benefit of IFN β-1a 44 μg SC tiw on relapse and MRI endpoints at 1 year in patients with RMS.