Post Hoc Analyses of PRISMS Study: Clinical Efficacy of Interferon beta-1a Subcutaneously Three Times Weekly According to Baseline Radiological Activity

Background: In the PRISMS study (N=560), subcutaneous interferon β-1a 44 μg three times weekly (IFN44) reduced relapses and delayed disability progression at Year 2 versus placebo (PBO), and at Year 4 in patients continuing IFN44 treatment compared with those re-randomized from PBO to IFN44 (PBO/IFN). The efficacy of IFN44 according to baseline radiological activity (BRA) has not been explored.

Objectives: To evaluate the clinical efficacy of IFN44 according to BRA in patients with relapsing–remitting MS in the PRISMS study.

Methods: The effects of IFN44 versus PBO/IFN on annualized relapse rate (ARR), time to relapse, and Expanded Disability Status Scale (EDSS) progression over 4 years were examined in patients in the PRISMS frequent-MRI cohort (patients receiving monthly T2 and gadolinium [Gd] scans before and during the first 9 months’ treatment). Patients were grouped into tertiles based on BRA (defined as the ratio of T2 or Gd lesions/disease duration [DD]).

Results: A priori cut-offs and lesion values=0 placed most patients in the lowest and middle BRA tertiles (n=101 to 114 and n=21 to 24, respectively) and led to an uneven distribution of data. In the highest BRA tertile (T2/DD >0.13 [n=24 and 24 for IFN44 and PBO, respectively]; Gd/DD >0.22 [n=20 and 27]), patients receiving IFN44 over 2 years showed reduced ARR, versus PBO (T2/DD 0.59 [0.37–0.94], rate ratio [RR] [95% CI]; Gd/DD 0.57 [0.36–0.91]). No significant between-treatment differences in ARR were observed in the middle or lowest tertiles. Patients receiving IFN44 in the highest tertile were less likely to relapse by Year 2 versus PBO (T2/DD 0.44 [0.23–0.85], hazard ratio [HR] [95% CI]; Gd/DD 0.31 [0.16–0.62]). The effects of IFN44 were maintained over 4 years versus PBO/IFN for ARR (T2/DD 0.53 [0.32–0.86], RR [95% CI]; Gd/DD 0.53 [0.34–0.81]) and time to relapse (T2/DD 0.41 [0.21–0.80], HR [95% CI]; Gd/DD 0.33 [0.17–0.63]). A delay in EDSS progression in patients grouped in the highest T2/DD tertile was observed at Year 1 (0.26 [0.07–0.95] HR [95% CI]). 

Conclusions: Clinical outcomes were significantly improved with early IFN44 treatment in patients with greater disease severity as measured by BRA. The impact of high BRA on relapses and disease progression will be explored further.