Matching-adjusted comparisons demonstrate better clinical outcomes in patients with relapsing multiple sclerosis treated with peginterferon beta-1a than with teriflunomide

Abstract

Background: Peginterferon beta-1a and teriflunomide are both first-line disease-modifying therapies (DMTs) approved for the treatment of relapsing multiple sclerosis (RMS); however, no head-to-head trials have directly compared their clinical efficacy. We performed a matching-adjusted comparison of individual patient data from the peginterferon beta-1a pivotal phase 3 study, ADVANCE, and its extension study, ATTAIN, with pooled aggregated data from the teriflunomide pivotal phase 3 studies, TEMSO and TOWER. Methods: A total of 512 patients randomized to subcutaneous (SC) peginterferon beta-1a 125 mcg every 2 weeks in ADVANCE and 731 patients randomized to teriflunomide 14 mg daily (359 from TEMSO and 372 from TOWER) were matched on key baseline characteristics. After matching, weighted annualized relapse rate (ARR) and 24-week confirmed disability worsening (CDW) were calculated and compared for peginterferon beta-1aand teriflunomide-treated patients. A subset analysis comparing weighted ARR in patients who were newly diagnosed with RMS (diagnosis ≤1 year before study enrollment and disease-modifying therapy naïve) was also performed. Results: After matching, the peginterferon beta-1a and teriflunomide treatment groups were identically matched across baseline characteristics. The proportion of patients in the overall study populations with 24-week CDW at 108 weeks was significantly lower in the peginterferon beta-1a group than the teriflunomide group both before matching (8.5% vs 12.6%; P = 0.0249) and after matching (8.4% vs 12.6%; P = 0.0323). ARR at 108 weeks was numerically lower with peginterferon beta-1a than with teriflunomide both before matching (0.278 vs 0.354; P = 0.1326) and after matching (0.257 vs 0.354; P = 0.0510). Newly diagnosed patients treated with peginterferon beta-1a had numerically lower ARR than patients treated with teriflunomide both at 108 weeks (before matching: 0.225 vs 0.270; P = 0.587; after matching: 0.201 vs 0.270; P = 0.384) and at 5 years (before matching: 0.150 vs 0.196; after matching: 0.142 vs 0.196). Conclusions: In this matching-adjusted comparison of patients with RMS from three phase 3 trials, a significantly lower proportion of patients treated with SC peginterferon beta-1a 125 mcg every 2 weeks than with oral teriflunomide 14 mg once daily had 24-week CDW at 108 weeks. In addition, in both the overall population and newly diagnosed patient subgroups, ARR at 108 weeks was numerically lower with peginterferon beta-1a than with teriflunomide. The numerically lower ARR in newly diagnosed patients treated with peginterferon beta-1a compared with those treated with teriflunomide was sustained through up to 5 years of treatment.

Real-world propensity score comparison of treatment effectiveness of peginterferon beta-1a vs. subcutaneous interferon beta-1a, glatiramer acetate, and teriflunomide in patients with relapsing-remitting multiple sclerosis

“…Our findings on ARRs from the real-world propensity score analysis of patients treated with peginterferon beta-1a vs. other platform DMTs are directionally similar to that found in 3 indirect comparisons of clinical trial data (Coyle et al, 2018;Scott et al, 2019;Newsome et al, 2020). An exception is that Coyle et al (2018) did find that peginterferon beta-1a was associated with a lower ARR than SC IFN beta-1a.…”

“…This divergence in findings may be from differences in baseline disease severity (e.g., number of relapses in 1-3 prior years, number of lesions) among study populations, alongside other differences between trial populations and patients in real-world settings. The 3 indirect matching-adjusted comparisons of treatment efficacy across clinical trial patients also provided evidence that peginterferon beta-1a treatment is associated with less confirmed disability worsening than SC IFN beta-1a, GA, and teriflunomide (Coyle et al, 2018;Scott et al, 2019;Newsome et al, 2020). We used claims for durable medical equipment as a proxy for disability worsening.…”

“…No head-to-head phase III clinical trials have compared the efficacy of peginterferon beta-1a with SC IFN beta-1a, GA, or teriflunomide. In indirect comparisons with matching-adjusted analyses of clinical trials, RRMS patients treated with peginterferon beta-1a compared to those treated with SC IFN beta-1a, GA, and teriflunomide had better clinical outcomes (Coyle et al, 2018;Scott et al, 2019;Newsome et al, 2020). There is limited direct comparative data in the published literature of the treatment effectiveness of peginterferon beta-1a vs. these other DMTs in the real-world setting.…”

<p>Re-Evaluating the Use of IFN-β and Relapsing Multiple Sclerosis: Safety, Efficacy and Place in Therapy</p>

“…The results showed that the proportion of patients with confirmed disability worsening at 108 weeks was significantly lower in the PEG IFNβ-1a group than the teriflunomide group, and that patients treated with PEG IFNβ-1a had lower annualized relapse rates at 108 weeks and 5 years compared to teriflunomide. 46 While these outcomes have been supported by other meta-analyses, there have been no randomized, head-to-head trial proving this.…”

“…Some evidence suggests that IFNβ therapy may be a superior option to teriflunomide when considering a lowerefficacy treatment. A recent study by Newsome et al 46 performed a matching-adjusted comparison of patient data from the ADVANCE and ATTAIN trials evaluating PEG IFNβ-1a to the TEMSO and TOWER studies evaluating teriflunomide. The results showed that the proportion of patients with confirmed disability worsening at 108 weeks was significantly lower in the PEG IFNβ-1a group than the teriflunomide group, and that patients treated with PEG IFNβ-1a had lower annualized relapse rates at 108 weeks and 5 years compared to teriflunomide.…”