Clinical and MRI Efficacy of IFN ß-1a SC tiw in MS Patients with More Advanced Disease (EDSS 4.0–6.0)

Background: Interferon beta-1a (IFN β-1a) 44 µg subcutaneously (SC) 3x weekly (tiw) reduced relapses and active T2 lesions in PRISMS over 2 years and in SPECTRIMS over 3 years, but significantly delayed disability progression vs placebo only in PRISMS. Understanding treatment effect in patients with more advanced disease (higher Expanded Disability Status Scale [EDSS]) is of interest.

Objectives: Use combined PRISMS and SPECTRIMS data to further characterize IFN β-1a 44 µg efficacy in patients with more advanced disease. 

Methods: In PRISMS, 560 RMS patients with EDSS 0–5.0 and ≥2 relapses in the past 2 years were randomly assigned to IFN β-1a 44 or 22 µg or placebo for 2 years. In SPECTRIMS, 618 patients with SPMS (EDSS increase ≥1 point over last 2 years [≥0.5 point if baseline (BL) EDSS 6.0–6.5]) and BL EDSS 3.0–6.5 were randomly assigned to IFN β-1a 44 or 22 µg or placebo for 3 years. These post hoc analyses examined relapses, T2 lesions, and 3-month confirmed progression (≥1 point EDSS increase [0.5 if BL ≥6.0]) at 1 and 2 years in patients receiving IFN β-1a 44 µg or placebo in a combined subgroup with EDSS 4.0–6.0. 

Results: IFN β-1a (n=171) reduced the annualized relapse rate vs placebo (n=164) by 36.6% (rate ratio [RR] 0.632 [95% confidence interval (CI) 0.496–0.805]; p=0.0002) at 1 year and 36.2% (RR 0.638 [0.507–0.803]; p=0.0001) at 2 years in the combined EDSS 4.0–6.0 subgroup. IFN β-1a reduced mean (standard deviation) numbers of active T2 lesions vs placebo at Months 6 (IFN β-1a, 0.6 [1.3] vs placebo, 2.4 [5.2]), 12 (0.5 [1.4] vs 2.3 [4.1]), and 24 (0.5 [1.5] vs 1.4 [2.9]). IFN β-1a reduced burden of disease (total T2 lesion area) from BL significantly more vs placebo through Month 24 (–31.1 [883.96] vs 455.8 [1110.9] mm²; p<0.0001). Further, IFN β-1a reduced disability progression risk at 1 year (hazard ratio [HR] 0.654 [95% CI 0.429–0.997]; p=0.0486 vs placebo) although not significant at 2 years (HR 0.740 [0.530–1.035]; p=0.0785). Data from patients with EDSS 4.0–6.0 still experiencing inflammatory activity (relapses or active MRI lesions) will be presented. Results of 6-month confirmed disability progression and time to EDSS progression will also be shown.  

Conclusions: Post hoc analyses indicate the effect of IFN β-1a 44 µg SC tiw to reduce relapses and T2 lesions and delay EDSS progression is not lost in a subgroup of MS patients with more advanced disease (EDSS 4.0–6.0), despite the inclusion of SPMS subjects in the pooled data set.