Peginterferon beta-1a in multiple sclerosis: 2-year results from ADVANCE

Abstract

Objective:To evaluate the efficacy and safety of subcutaneous peginterferon beta-1a over 2 years in patients with relapsing–remitting multiple sclerosis in the ADVANCE study.Methods:Patients were randomized to placebo or 125 µg peginterferon beta-1a every 2 or 4 weeks. For Year 2 (Y2), patients originally randomized to placebo were re-randomized to peginterferon beta-1a every 2 weeks or every 4 weeks. Patients randomized to peginterferon beta-1a in Year 1 (Y1) remained on the same dosing regimen in Y2.Results:Compared with Y1, annualized relapse rate (ARR) was further reduced in Y2 with every 2 week dosing (Y1: 0.230 [95% CI 0.183–0.291], Y2: 0.178 [0.136–0.233]) and maintained with every 4 week dosing (Y1: 0.286 [0.231–0.355], Y2: 0.291 [0.231–0.368]). Patients starting peginterferon beta-1a from Y1 displayed improved efficacy versus patients initially assigned placebo, with reductions in ARR (every 2 weeks: 37%, p<0.0001; every 4 weeks: 17%, p=0.0906), risk of relapse (every 2 weeks: 39%, p<0.0001; every 4 weeks: 19%, p=0.0465), 12-week disability progression (every 2 weeks: 33%, p=0.0257; every 4 weeks: 25%, p=0.0960), and 24-week disability progression (every 2 weeks: 41%, p=0.0137; every 4 weeks: 9%, p=0.6243). Over 2 years, greater reductions were observed with every 2 week versus every 4 week dosing for all endpoints and peginterferon beta-1a was well tolerated.Conclusions:Peginterferon beta-1a efficacy is maintained beyond 1 year, with greater effects observed with every 2 week versus every 4 week dosing, and a similar safety profile to Y1.Clinicaltrials.gov Registration Number: NCT00906399.

ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

“…37 Those statements that could not be approved during the face-to-face meeting due to time limitations were evaluated in a third round via e-mail. Extension studies available for four of the interferon pivotal trials concluded that the early-intervention group had a lower annualized relapse rate and fewer new or newly enlarging T2 lesions at 2 and 4 years' follow-up, 54,55 as well as a lower proportion of participants with disability worsening at 2 and 8 years' follow-up. 55,56 At 16 years' follow-up, there was little difference between the early-and delayed-treatment groups in the number of participants reaching an EDSS score of 6 and those converting to secondary-progressive MS. 57 Further details about the study outcomes can be found in Supplementary Appendix 8.…”

“…55,56 At 16 years' follow-up, there was little difference between the early-and delayed-treatment groups in the number of participants reaching an EDSS score of 6 and those converting to secondary-progressive MS. 57 Further details about the study outcomes can be found in Supplementary Appendix 8.…”

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

“…The peginterferon beta-1a safety profile was similar to established interferon beta treatments; injection-site reactions, influenza-like symptoms, pyrexia, and headache were the most commonly reported treatment-related adverse events (AEs) [Calabresi et al 2014;Kieseier et al 2015]. Significant benefits on disability outcomes were also demonstrated: peginterferon beta-1a 125 mcg every 2 weeks reduced the risk of 12-week CDP by 38% (p = 0.038) compared with placebo in year 1 [Calabresi et al 2014], with the benefit maintained through year 2 [Kieseier et al 2015] (Supplementary Table 1). …”

“…Its efficacy was established in the 2-year, phase III ADVANCE study, in which peginterferon beta-1a significantly reduced relapse rates and improved MRI measures, compared with placebo over 1 year, in patients with relapsing-remitting MS (RRMS), with clinical and MRI benefits maintained through year 2 [Calabresi et al 2014;Kieseier et al 2015]. The peginterferon beta-1a safety profile was similar to established interferon beta treatments; injection-site reactions, influenza-like symptoms, pyrexia, and headache were the most commonly reported treatment-related adverse events (AEs) [Calabresi et al 2014;Kieseier et al 2015].…”

“…Its efficacy was established in the 2-year, phase III ADVANCE study, in which peginterferon beta-1a significantly reduced relapse rates and improved MRI measures, compared with placebo over 1 year, in patients with relapsing-remitting MS (RRMS), with clinical and MRI benefits maintained through year 2 [Calabresi et al 2014;Kieseier et al 2015]. The peginterferon beta-1a safety profile was similar to established interferon beta treatments; injection-site reactions, influenza-like symptoms, pyrexia, and headache were the most commonly reported treatment-related adverse events (AEs) [Calabresi et al 2014;Kieseier et al 2015]. Significant benefits on disability outcomes were also demonstrated: peginterferon beta-1a 125 mcg every 2 weeks reduced the risk of 12-week CDP by 38% (p = 0.038) compared with placebo in year 1 [Calabresi et al 2014], with the benefit maintained through year 2 [Kieseier et al 2015] (Supplementary Table 1).…”