Peginterferon Beta-1a May Improve Recovery Following Relapses in the ADVANCE Relapsing-Remitting Multiple Sclerosis Study

Background: In relapsing-remitting multiple sclerosis (RRMS) study populations on placebo, approximately 30% of all relapses have been reported to lead to confirmed disability progression (DP). Given the 36% and 28% reductions in annualized relapse rate (ARR) seen for investigational subcutaneous peginterferon beta-1a (PEG-IFN; 125 µg) every 2 (Q2W) or 4 (Q4W) weeks, respectively versus placebo, at Year 1 of the ADVANCE study, this treatment effect is unlikely to provide the only explanation for the relative 38% reduction in risk of 12-week confirmed DP seen for Q2W and Q4W.

Objectives: To determine whether PEG-IFN improved recovery following relapses (RfR) versus placebo in RRMS patients, and to examine the relationship between change in individual functional systems scores (FSS) during a relapse and following sustained DP.

Methods: Post-hoc analyses were conducted using data from patients randomized and dosed in ADVANCE (n=1512). DP due to incomplete RfR was defined as onset of 3-month sustained DP (≥1.0- or ≥1.5-point increase in Expanded Disability Status Scale score, from respective baseline scores of ≥1.0 or 0.0, confirmed after 12 weeks) within 180 days of a relapse. Simultaneous worsening of FSS was defined as a ≥1 point change in FSS caused by a relapse, with the same FSS being part of the sustained DP. 

Results: Overall, n=55 experienced DP associated with relapses; n=57 experienced DP not associated with relapses (numerically fewer on PEG-IFN versus placebo). Relapse severities were not different between groups. Approximately 90% with sustained DP had ≥1 FSS that had simultaneous worsening during the preceding relapse; this was evident in 87% within 15 days of the most recent relapse (most frequent in pyramidal [55.3-55.7%]). PEG-IFN Q2W and Q4W reduced the proportion of patients experiencing sustained DP due to incomplete RfR versus placebo by 56% (p=0.012) and 41% (p=ns), respectively. Following a recent relapse, a lower proportion receiving PEG-IFN Q2W (13.6%) and Q4W (15.2%) had sustained DP versus placebo (19.6%); indicating relative reductions in risk of DP following any relapse of 30% and 22%, respectively.

Conclusions: PEG-IFN, compared with placebo, significantly improved RfR. Approximately half of patients with sustained DP in Year 1 of ADVANCE did not have an associated relapse. Simultaneous worsening of pyramidal FSS accounted for the majority of sustained DP, which occurred less frequently in PEG-IFN-treated patients.