Matching-Adjusted Comparisons Demonstrate Better Clinical Outcomes with SC Peginterferon Beta-1a Every Two Weeks Than with SC Interferon Beta-1a Three Times per Week

Abstract Background Subcutaneous (SC) peginterferon beta-1a and SC interferon beta-1a (IFN beta-1a) have demonstrated efficacy in treating relapsing-remitting multiple sclerosis (RRMS) but have never been compared in direct head-to-head clinical trials, the gold-standard comparison. A well-balanced matching-adjusted comparison of weighted individual patient data on SC peginterferon beta-1a, and aggregate data from published phase 3 clinical trials of SC IFN beta-1a, was conducted to provide additional information on the comparative efficacy of these two agents. Methods Individual patient data from a study of SC peginterferon beta-1a 125mcg every two weeks (ADVANCE) and pooled summary data from four published studies of SC IFN beta-1a 44mcg three times per week (OPERA I and II, CARE-MS I and II) with similar populations were utilized. A comparison was conducted by weighting individual peginterferon beta-1a-treated patients, using estimated propensity of enrolling in SC IFN beta-1a treatment to match multiple key aggregate baseline characteristics of SC IFN beta-1a-treated patients. After matching, weighted annualized relapse rate (ARR), 24-week confirmed disability worsening (CDW), and clinical no evidence of disease activity (clinical-NEDA) were calculated and compared for peginterferon beta-1a and SC IFN beta-1a. Results After matching, baseline characteristics were well balanced across treatment groups. At 2 years, ARR after matching was 0.256 for patients receiving peginterferon beta-1a (effective n=376) and 0.335 for those receiving SC IFN beta-1a (n=1218) ( P =0.0901). The percentage of patients who were relapse free over 2 years was significantly higher with peginterferon beta-1a than with SC IFN beta-1a (75.1% vs. 57.4% [after matching], P P =0.0007). Clinical-NEDA occurred in a significantly higher proportion of patients treated with SC peginterferon beta-1a versus SC IFN beta-1a (74.1% vs. 48.1%; P Conclusions This matching-adjusted comparison using data from four phase 3 trials with SC IFN beta-1a formulations demonstrated that patients with RRMS treated with SC peginterferon beta-1a 125mcg every two weeks achieved better clinical outcomes than patients who received SC IFN beta-1a 44mcg three times per week.