Pegylated interferon beta-1a for relapsing-remitting multiple sclerosis (ADVANCE)
Here the researchers report primary results from the first 48 weeks (placebo-controlled period) of the two-year, phase 3, ADVANCE study assessing the efficacy and safety of peginterferon beta-1a administered every two or every four weeks for patients with relapsing-remitting multiple sclerosis.
Patients were randomly assigned (1:1:1) to receive subcutaneous injections with pre-filled syringes of placebo, peginterferon beta-1a at a dose of 125 μg once every two weeks, or peginterferon beta-1a 125 μg once every four weeks. Patients received either study drug or placebo every two weeks to maintain masking. They did standardised neurological assessments, including the Expanded Disability Status Scale, at screening, at baseline, every 12 weeks, and at the time of suspected relapse (evaluated during unscheduled visits). Patients had MRI scans at screening and at weeks 24 and 48. The primary endpoint was annualised relapse rate at week 48, based on number of relapses. Secondary efficacy endpoints were the number of new or newly enlarging hyperintense lesions on T2-weighted images (relative to baseline MRI), proportion of patients who relapsed, and proportion of patients with disability progression at 48 weeks. Tertiary pre-specified MRI endpoints at 48 weeks were the number of gadolinium-enhancing lesions, new T1 hypointense lesions, and new active lesions (sum of gadolinium-enhancing plus non-enhancing new or newly enlarging T2 hyperintense lesions), the volume of new or newly enlarging T2 hyperintense and T1 hypointense lesions, brain atrophy, and magnetisation transfer ratio. 1512 patients received at least one dose of study drug and were included in the intention-to-treat population.
Relapses were significantly less frequent in patients taking peginterferon beta-1a than in those taking placebo. Patients treated with peginterferon beta-1a had fewer new or newly enlarging hyperintense lesions on T2-weighted images at 48 weeks than did patients in the placebo group. The most commonly reported treatment-related adverse events were injection-site reactions, influenza-like illness, and headache. The incidence of serious adverse events was similar in each group.
Calabresi PA, Kieseier BC
Lancet Neurol. 2014 Apr 30. pii: S1474-4422(14)70068-7. doi: 10.1016/S1474-4422(14)70068-7. [Epub ahead of print]
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