Efficacy and Safety of Peginterferon Beta-1a in Relapsing-Remitting Multiple Sclerosis: 2-Year Data from the ADVANCE Study

Background: At Year 1 of ADVANCE, subcutaneous peginterferon beta-1a (PEG-IFN; 125 µg every 2 [Q2W] or 4 [Q4W] weeks) significantly reduced annualized relapse rate (ARR; primary endpoint), risk of relapse, risk of 12-week confirmed disability progression, and the number of new or newly-enlarging T2 lesions versus placebo. Safety profiles were similar for Q2W and Q4W treatment arms, and consistent with established interferon beta-1a therapies.

Objectives: To further evaluate the efficacy and safety of investigational PEG-IFN in patients with relapsing-remitting multiple sclerosis (RRMS) in the on-going Phase 3, ADVANCE study. We present 24-week confirmed disability progression data at Year 1 and interim 2-year efficacy and safety data.

Methods:  Year 1 data were analyzed post-hoc to determine the proportion of patients with disability progression (defined by a ≥1.0- or ≥1.5-point increase in Expanded Disability Status Scale score, from a baseline score of ≥1.0 or 0.0, respectively) sustained over 24 weeks. During Year 2, all patients received dose-blinded PEG-IFN (at the end of Year 1 patients on placebo were re-randomized to PEG-IFN 125 µg Q2W or Q4W). Interim 2-year analyses of efficacy and safety were conducted for patients with 2 years of data at cut-off. Post-hoc analyses compared the efficacy of Q2W versus Q4W regimens.

Results: In the intent-to-treat population (placebo n=500; PEG-IFN Q2W n=512; PEG-IFN Q4W n=500), 24-week confirmed disability progression data at Year 1 reflected the significantly reduced risk of 12-week confirmed disability progression observed for PEG-IFN Q2W versus placebo at Year 1. For patients continuing PEG-IFN in Year 2, ARR was maintained (for Q4W) or further numerically reduced (for Q2W) relative to Year 1. New or newly-enlarging T2 lesions were numerically lower in Year 2 versus Year 1 for patients continuing Q2W and Q4W. Over 2 years, versus those originally assigned to placebo, reductions in ARR, risk of relapse and risk of 12-week confirmed disability progression were seen for patients on PEG-IFN during both Years 1 and 2. PEG-IFN Q2W provided numerically larger treatment effects over 2 years versus Q4W. Over 2 years, PEG-IFN was well tolerated, with a safety profile consistent with Year 1 of ADVANCE and other beta interferons.

Conclusions: Results for 24-week confirmed disability progression at Year 1 and interim 2-year data support the maintained benefits of PEG-IFN Q2W in RRMS.