Early and Consistent Benefits of Interferon Beta-1a SC in Relapsing Multiple Sclerosis: Post Hoc Analysis of Prisms MRI Data

Background: In results of the 2-year PRISMS-2 study (PRISMS, Lancet 1998;352:1498–1504), interferon beta-1a given subcutaneously (IFN β-1a SC) reduced disease activity on magnetic resonance imaging (MRI) scans vs placebo among patients with relapsing multiple sclerosis (RMS). 

Objectives: Investigate monthly differences in active lesions and MRI scans in patients with RMS receiving placebo or IFN β-1a SC over 9 months.

Methods: 560 adults with RMS having had ≥2 relapses over 2 years, with Expanded Disability Status Scale score 0–5.0, were randomized to placebo or IFN β-1a SC 22 or 44 µg, 3x/week for 2 years. A cohort (n=198) underwent monthly MRI scans for the first 9 months. Post hoc analysis of this cohort determined mean number of combined unique (CU) active lesions (combined count of proton density [PD]/T2 and T1 gadolinium enhanced [Gd+] new and recurring lesions; unique means an active lesion on both PD/T2 and T1 Gd+ scans was only counted once) per patient per scan, and percentages of combined active scans (scans with CU active lesions) per patient. For each monthly point, pairwise between-treatment comparisons including all scans up to that point were assessed using ANOVA models on ranks adjusting for number of CU active lesions at baseline and study center. Percentages of patients with no active scans at each month were calculated.

Results: As early as up to 2 months (including 4–8 weeks titration), for mean CU active lesions/patient/scan, means (medians) were 1.92 (0.75), 1.40 (0.25), and 0.77 (0.00) for placebo (n=66) and IFN β-1a SC 22 µg (n=64) and 44 µg (n=67), respectively (p<0.01 for 22 and 44 µg vs placebo). Among scans up to 2 months, mean (median) % combined active scans/patient were 55.3% (50%), 36.7% (25%), and 32.1% (0%) for placebo, 22 µg, and 44 µg groups respectively (p<0.01 for 22 and 44 µg vs placebo). Differences between each IFN β-1a SC group and placebo in mean CU active lesions and % combined active scans were significant at subsequent monthly points up to 9 months (p=NS for 22 vs 44 µg). At Month 2, 42.9%, 67.2%, and 78.1% of placebo, 22 µg, and 44 µg patients, respectively, had no active scans. This rose to 49.2%, 84.4%, and 88.2% at Month 9 (in 65, 64, and 68 placebo, 22 µg, and 44 µg patients with valid scans). 

Conclusions: Results support an early (2 months) and consistent treatment-associated reduction of CU active lesions and combined active scans among patients with RMS receiving IFN β-1a SC vs placebo.