Peginterferon Beta-1a Advance Study: Subgroup Analysis over 2 Years

Background: ADVANCE was a 2-year, double-blind, placebo-controlled, Phase III study in patients aged 18–65 years with relapsing-remitting MS (RRMS) which demonstrated that peginterferon beta-1a 125 mcg administered subcutaneously every 2 or 4 weeks led to significant reductions in ARR compared with placebo.

Objectives: To describe subgroup analyses of annualised relapse rate (ARR) over 2 years in the ADVANCE study.

Methods: 1512 patients were treated with peginterferon beta-1a 125 mcg every 2 weeks or every 4 weeks, or placebo during Year 1. Thereafter, patients on placebo were re-randomized to peginterferon beta-1a every 2 weeks or every 4 weeks (delayed treatment). Subgroup analyses (pre-specified for Year 1, repeated at Year 2) were conducted by demographics (age, gender, weight, BMI, and geographical region) and baseline disease characteristics (number of prior relapses, time since most recent relapse, McDonald criteria, prior MS treatment, Expanded Disability Status Scale (EDSS), volume of T2 hyperintense lesions, and presence of gadolinium-enhancing lesions (Gd+)). The following results compared ARR in these subgroups for patients in continuous 2 week treatment with continuous 4-week treatment.

Results: ARR was similar in most demographic and baseline disease characteristic subgroups evaluated within the peginterferon beta-1a every 2 week arm or every 4 week arm over 2 years. Although for both doses some differences in the point estimates for the ARR were noted among the subgroups, considerable overlap in the confidence intervals suggested that the efficacy of peginterferon beta-1a is similar in all patients irrespective of gender, age, body weight, geographical region and disease activity at initiation of treatment. In some subgroups analyzed (number of relapses in prior 3 years = 3,  time since most recent relapse ≤ median, McDonald Criteria of 1, EDSS < 4, no prior MS treatment, Gd+ lesions absent, T2 lesion volume < median, female, age < 40 years) ARR reduction reached significance in subjects treated with peginterferon beta-1a every 2 weeks compared with peginterferon beta-1a every 4 weeks.

Conclusions: Within each peginterferon beta-1a dosing group, ARR was generally similar across most subgroups. Further, peginterferon beta-1a every 2 weeks demonstrated significant reductions in ARR versus peginterferon beta-1a every 4 weeks in some subgroups tested. 

Study sponsored by: Biogen Idec Inc. (Cambridge, MA, USA).