• Neurology Clinical Trials
• Demyelinating Diseases

• Neurology Clinical Trials
• Demyelinating Diseases
• Neurology

Significantly more subjects with relapsing-remitting multiple sclerosis (RRMS) achieved freedom from measured disease activity (FMDA) when treated with peginterferon beta-1a every 2 weeks (Q2W) compared with those who were treated with peginterferon beta-1a every 4 weeks (Q4W) or placebo, said Douglas Arnold, MD, McGill University, Montreal, Quebec, Canada, who presented results from a post hoc analysis of 48-week data from the Efficacy and Safety Study of BIIB017 (PEGylated Interferon Beta-1a) in Participants With Relapsing Multiple Sclerosis trial [ADVANCE; NCT00906399].

ADVANCE was a Phase 3 multicenter double-blind study with subjects with RRMS and an Expanded Disability Status Scale (EDSS) £5, who were randomly assigned to treatment with peginterferon beta-1a 125 μg Q2W or Q4W for 96 weeks or to placebo for 48 weeks, then 1 of the 2 peginterferon beta-1a dosing regimens for 48 weeks. Magnetic resonance imaging (MRI) was conducted at baseline and Weeks 24 and 48. Participants were assessed for

1. MRI freedom from measured disease activity (FMDA; defined as no gadolinium-enhancing [Gd+] lesions and no new or newly enlarging T2 lesions at Week 48 compared with baseline)

2. clinical freedom from measured disease activity (defined as no relapses or 12-week confirmed disability progression over 48 weeks), and

3. a composite of both conditions (overall FMDA). A sensitivity analysis was performed using a definition with minimal MRI allowance (no Gd+ lesions at Weeks 24 and 48 and ≤1 new or newly enlarging T2 lesions at Week 48 compared with baseline).

The primary outcome was annualized relapse rate (ARR) at Week 48.

Subjects (n=1516) had a mean age of approximately 36 years, approximately 71% were women, and most (−82%) were white. The mean time since first MS symptom was 6.5 years. A mean of 1.6 relapses had occurred within the previous 12 months. Mean EDSS score was 2.46, and mean T2 lesions and GD+ lesions were 50 and 1.5, respectively.

The primary results of ADVANCE showed that after 48 weeks, both peginterferon beta-1a dose regimens were associated with a significantly reduced relapse rate compared with placebo. These results have already been published [Calabresi PA et al. Lancet Neurol 2014]. Additionally, interim 2-year results support the maintenance of benefit and the significantly greater efficacy of the Q2W dose regime (vs the Q4W regime) [Deykin A et al. Neurology 2014].

The objective of the post hoc analysis presented by Dr. Arnold was to assess FMDA in patients treated with peginterferon beta-1a during Year 1 of ADVANCE. Results of the analysis showed that significantly more subjects receiving Q2W dosing achieved overall FMDA from baseline to Week 48 (33.9%) compared with those receiving placebo (15.1%; p<0.0001) or Q4W dosing (21.5%; p<0.0001). Between Week 24 and Week 48, 60.2% of subjects receiving Q2W dosing achieved FMDS compared with 28.9% receiving placebo (p<0.0001) or Q4W dosing (36.6%; p<0.0001) Subjects on the Q4W dosing were more like to achieve overall FMDA than were those receiving placebo.

Among subjects achieving MRI FMDA only, significantly (p<0.0001) higher proportions were from the group receiving Q2W dosing compared with those receiving placebo or Q4W dosing at both time points. Subjects in the Q4W dosing group were significantly (p<0.05) more likely to achieve MRI FMDA compared with those receiving placebo.

At both time points (baseline to Week 48 or Week 24 to Week 48), subjects in the Q2W dosing group were significantly (p<0.001) more likely to achieve clinical FMDA than were those receiving placebo or Q4W dosing. However, the proportion of patients achieving clinical FMDA was not significantly different between the 2 peginterferon beta-1a dosing regimens.

The robustness of these findings was confirmed with sensitivity analyses allowing for minimal MRI activity. Peginterferon beta-1a Q2W values were significantly (p<0.0001) greater than placebo and Q4W values. Q4W values were significantly (p<0.02) greater than placebo values.

These data, along with previous findings, support the use of peginterferon beta-1a as an effective treatment for patients with RRMS, with the benefit of less frequent subcutaneous administration.

• © 2014 MD Conference Express®