Post Hoc Analysis of PRISMS Study: Efficacy of Interferon beta-1a Subcutaneously Three Times Weekly According to Baseline EDSS/Duration, EDSS, and MSSS Subgroups

Background: In the PRISMS study (N=560), subcutaneous interferon β-1a 44 µg three times weekly (IFN44) reduced relapses and delayed Expanded Disability Status Scale (EDSS) progression at Year 2 compared to placebo (PBO). Consistent effects were maintained at Year 4 in patients continuing IFN44 compared to patients re-randomized from PBO to IFN44 after 2 years (PBO/IFN). The efficacy of IFN44 according to disease severity is not completely understood.

Objectives: To determine the clinical efficacy of IFN44 according to baseline disease characteristics in patients with relapsing–remitting multiple sclerosis (RRMS) in the frequent-magnetic resonance imaging (MRI) cohort (patients receiving monthly T2 and gadolinium scans before and during the first 9 months of treatment) in the PRISMS study.

Methods: Patients were grouped into tertiles of baseline levels of disease severity as follows: ratio of EDSS/duration of disease (lowest tertile: ≤0.27, middle: >0.27 to ≤0.64, highest: >0.64), EDSS (<2, ≥2 to ≤3, >3), and MS Severity Scale (MSSS; ≤2.87, >2.87 to ≤5.24, >5.24). The effects of IFN44 compared to PBO/IFN on annualized relapse rate (ARR) and EDSS progression (defined as ≥1- or ≥0.5-point increase from baseline ≤5.5 or ≥6, respectively, sustained ≥3 months) were examined at Years 2 and 4.

Results: At Year 2, IFN44 reduced ARR compared to PBO in the highest and middle EDSS/duration tertiles (rate ratio [RR] [95% confidence interval (CI)] 0.55 [0.40–0.76], p=0.0002 and 0.65 [0.48–0.86], p=0.0028], respectively), in the highest and middle tertiles of EDSS (RR [95% CI] 0.51 [0.37–0.70], p<0.0001 and 0.74 [0.57–0.97], p=0.0307), and in the highest and middle tertiles of MSSS (RR [95% CI] 0.64 [0.48–0.86], p=0.0027 and 0.55 [0.41–0.75], p=0.0001). The effects of IFN44 were maintained at Year 4. No significant between-treatment differences in ARR were observed in the lowest tertiles of EDSS/duration of disease, EDSS, and MSSS at Year 2 and Year 4. Over 4 years, IFN44 significantly delayed time to first sustained EDSS progression compared to PBO/IFN in the highest EDSS tertile (hazard ratio [95% CI] 0.55 [0.316–0.968], p=0.0381).

Conclusions: Clinical benefits were significantly improved with early IFN44 treatment in patients with high or moderate baseline EDSS/duration of disease, EDSS, and MSSS. The effects of IFN44 in subgroups stratified by baseline disease characteristics were consistent with overall results of the extension phase of PRISMS.