Peginterferon beta-1a reduces disability worsening in relapsing-remitting multiple sclerosis: 2-year results from ADVANCE

Abstract

Background: In the pivotal phase III 2-year ADVANCE study, subcutaneous peginterferon beta-1a 125 mcg every 2 weeks demonstrated significant improvements in clinical outcomes, including disability endpoints, in patients with relapsing-remitting multiple sclerosis (RRMS). Here, we aim to further evaluate disability data from ADVANCE, and explore associations between confirmed disability progression (CDP), functional status, and health-related quality of life (HRQoL).

Methods: In total, 1512 patients were randomized to placebo or peginterferon beta-1a 125 mcg every 2 or 4 weeks. After 1 year, patients on placebo were re-randomized to peginterferon beta-1a every 2 or 4 weeks. CDP was defined as ⩾1.0 point increase from a baseline Expanded Disability Status Scale (EDSS) score ⩾ 1.0, or ⩾1.5-point increase from baseline 0, confirmed 12 or 24 weeks after onset.

Results: Peginterferon beta-1a every 2 weeks significantly reduced risk of 12- and 24-week CDP at 1 year compared with placebo (12-week CDP: 6.8% versus 10.5%, p = 0.038; 24-week CDP: 4% versus 8.4%, p = 0.0069, peginterferon beta-1a every 2 weeks versus placebo, respectively). Benefits were maintained over 2 years (11.2% and 7.7%, peginterferon beta-1a every 2 weeks in 12- and 24-week CDP, respectively). Approximately 90% of patients with 24-week CDP had simultaneous worsening by ⩾1 point in at least one functional system score, most commonly pyramidal. Displaying a 24-week CDP was associated with worse scores on the Multiple Sclerosis Functional Composite (MSFC) scale and several HRQoL instruments; the impact of CDP was attenuated by treatment with peginterferon beta-1a every 2 weeks.

Conclusions: Peginterferon beta-1a has the potential to prevent/delay worsening of disability in patients with relapsing-remitting multiple sclerosis. Furthermore, improved benefits in disability status with peginterferon beta-1a were also associated with improved functional status and HRQoL [ClinicalTrials.gov identifier: NCT00906399].

Keywords: functional score disability evaluation; multiple sclerosis; patient-reported outcomes; peginterferon beta-1a; pegylated interferon; phase III clinical trial; relapsing–remitting multiple sclerosis.

Conflict of interest statement

Conflict of interest statement: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SDN has participated in scientific advisory boards for Biogen, Genzyme, and Novartis, and has received research support from Biogen, Novartis, and the National MS Society. BCK was not affiliated to Biogen at the time of study conduct and data analysis, but is now an employee and stock holder of Biogen. SL, XY, EK, SH, and BS are employees and stockholders of Biogen.

Figures

Figure 1.

Proportions of patients with 24-week confirmed disability progression over 1 year. *Based on a Cox proportional hazards model adjusted for baseline EDSS and age (< 40 versus ⩾ 40 years). $Kaplan–Meier estimate. CDP defined as ⩾1.0-point increase on the EDSS from a baseline EDSS ⩾ 1.0, or ⩾ 1.5-point increase on the EDSS from a baseline EDSS of 0, confirmed 24 weeks after onset. CDP, confirmed disability progression; CI, confidence interval; EDSS, Expanded Disability Status Scale; ITT, intent-to-treat.

Figure 2.

Proportions of patients with 24-week confirmed disability progression over 2 years, based on worsening on Expanded Disability Status Scale by ⩾ 1.0 point from baseline *Based on a Cox proportional hazards model adjusted for baseline EDSS and age (< 40 versus ⩾ 40 years). $Kaplan–Meier estimate. CDP defined as ⩾1.0-point increase on the EDSS from a baseline EDSS

Figure 3.

Proportions of patients with (A) 12-week confirmed disability progression (CDP) in year 1, (B) 24-week CDP in year 1, (C) 12-week CDP over 2 years, and (D) 24-week CDP over 2 years, with simultaneous worsening of ⩾1 point in any functional system score. (A) n = 106 patients with 12-week CDP [excludes six patients (from a total of 112 patients across all treatment groups) who had unevaluable FSS information]. (B) n = 82 patients with 24-week CDP [excludes one patient (from a total of 83 patients across all treatment groups) who had unevaluable FSS information]. (C) n = 157 patients with 12-week CDP [excludes 25 patients (from a total of 182 patients across all treatment groups) who had unevaluable FSS information]. (D) n = 112 patients with 24-week CDP [excludes 31 patients (from a total of 143 patients across all treatment groups) who had unevaluable FSS information]. CDP, confirmed disability progression; FSS, functional system score.