Effect of peginterferon beta-1a on MRI measures and achieving no evidence of disease activity: results from a randomized controlled trial in relapsing-remitting multiple sclerosis

Douglas L Arnold, Peter A Calabresi, Bernd C Kieseier, Sarah I Sheikh, Aaron Deykin, Ying Zhu, Shifang Liu, Xiaojun You, Bjoern Sperling, Serena Hung

BackgroundSubcutaneous peginterferon beta-1a provided clinical benefits versus placebo at Year 1 of the 2-Year Phase 3 ADVANCE study in relapsing-remitting multiple sclerosis (RRMS). Here we report its effect on brain magnetic resonance imaging (MRI) lesions, and no evidence of disease activity (NEDA; absence of clinical [relapses and 12-week confirmed disability progression] and MRI [gadolinium-enhancing, and new or newly-enlarging T2 hyperintense lesions] disease activity).MethodsRRMS patients (18¿65 years; Expanded Disability Status Scale score ¿5) were randomized to double-blind placebo or peginterferon beta-1a 125 ¿g every 2 or 4 weeks. Sensitivity analyses of last observation carried forward and composite disease activity (using minimal MRI allowance definitions) were conducted.Results1512 patients were randomized and dosed (placebo n¿=¿500; peginterferon beta-1a every 2 [n¿=¿512] or 4 [n¿=¿500] weeks). Every 2 week dosing significantly reduced, versus placebo and every 4 week dosing, the number of new or newly-enlarging T2 hyperintense lesions at Weeks 24 (61% and 51%, respectively) and 48 (secondary endpoint; 67% and 54%, respectively); all p¿<¿0.0001. Every 2 week dosing also significantly reduced the number of new T1 hypointense, gadolinium-enhancing, and new active (gadolinium-enhancing plus non-enhancing new T2) lesions (all p¿<¿0.0001), as well as the volume of T2 and T1 lesions (p¿<¿0.05) at Weeks 24 and 48 versus placebo and every 4 week dosing. Significantly more patients dosed every 2 weeks had NEDA versus placebo and every 4 weeks (all p¿<¿0.01) from baseline to Week 48 (33.9% versus 15.1% and 21.5%, respectively [odds ratios, ORs: 2.89 and 1.87]), from baseline to Week 24 (41.0% versus 21.9% and 30.7%, [ORs: 2.47 and 1.57]) and from Week 24 to Week 48 (60.2% versus 28.9% and 36.6%, [ORs: 3.71 and 2.62]). Consistent results were seen allowing for minimal MRI activity.ConclusionDuring Year 1 of ADVANCE, significantly more RRMS patients receiving peginterferon beta-1a every 2 weeks had NEDA, and early and sustained improvements in MRI endpoints, versus placebo and every 4 week dosing. Sensitivity analyses align with switch strategies in clinical practice settings and provide insight into future responders/non-responders.Trial registrationClinicalTrials.gov: NCT00906399.