Pegylated interferon beta-1a for relapsing-remitting multiple sclerosis (ADVANCE): A randomised, phase 3, double-blind study

Peter Calabresi, Bernd C. Kieseier, Douglas L. Arnold, Laura J. Balcer, Alexey Boyko, Jean Pelletier, Shifang Liu, Ying Zhu, Ali Seddighzadeh, Serena Hung, Aaron Deykin

Research output: Contribution to journalArticle

Abstract

Background: Subcutaneous pegylated interferon (peginterferon) beta-1a is being developed for treatment of relapsing multiple sclerosis, with less frequent dosing than currently available first-line injectable treatments. We assessed the safety and efficacy of peginterferon beta-1a after 48 weeks of treatment in the placebo-controlled phase of the ADVANCE trial, a study of patients with relapsing-remitting multiple sclerosis. Methods: We did this 2-year, double-blind, parallel group, phase 3 study, with a placebo-controlled design for the first 48 weeks, at 183 sites in 26 countries. Patients with relapsing-remitting multiple sclerosis (age 18-65 years, with Expanded Disability Status Scale score ≤5) were randomly assigned (1:1:1) via an interactive voice response or web system, and stratified by site, to placebo or subcutaneous peginterferon beta-1a 125 μg once every 2 weeks or every 4 weeks. The primary endpoint was annualised relapse rate at 48 weeks. This trial is registered with ClinicalTrials.gov, number NCT00906399. Findings: We screened 1936 patients and enrolled 1516, of whom 1512 were randomly assigned (500 to placebo, 512 to peginterferon every 2 weeks, 500 to peginterferon every 4 weeks); 1332 (88%) patients completed 48 weeks of treatment. Adjusted annualised relapse rates were 0·397 (95% CI 0·328-0·481) in the placebo group versus 0·256 (0·206-0·318) in the every 2 weeks group and 0·288 (0·234-0·355) in the every 4 weeks group (rate ratio for every 2 weeks group 0·644, 95% CI 0·500-0·831, p=0·0007; rate ratio for the every 4 weeks group 0·725, 95% CI 0·565-0·930, p=0·0114). 417 (83%) patients taking placebo, 481 (94%) patients taking peginterferon every 2 weeks, and 472 (94%) patients taking peginterferon every 4 weeks reported adverse events including relapses. The most common adverse events associated with peginterferon beta-1a were injection site reactions, influenza-like symptoms, pyrexia, and headache. 76 (15%) patients taking placebo, 55 (11%) patients taking study drug every 2 weeks, and 71 (14%) patients taking study drug every 4 weeks reported serious adverse events; relapse, pneumonia, and urinary tract infection were the most common. Interpretation: After 48 weeks, peginterferon beta-1a significantly reduced relapse rate compared with placebo. The drug might be an effective treatment for relapsing-remitting multiple sclerosis with less frequent administration than available treatments. Funding: Biogen Idec.

Original languageEnglish (US)
Pages (from-to)657-665
Number of pages9
JournalThe Lancet Neurology
Volume13
Issue number7
DOIs
StatePublished - 2014

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Relapsing-Remitting Multiple Sclerosis
Double-Blind Method
Placebos
Interferons
Recurrence
Therapeutics
Interferon beta-1a
Pharmaceutical Preparations
Injections
Urinary Tract Infections
Human Influenza
Multiple Sclerosis
Headache
Pneumonia
Fever
Safety

ASJC Scopus subject areas

  • Clinical Neurology

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Pegylated interferon beta-1a for relapsing-remitting multiple sclerosis (ADVANCE) : A randomised, phase 3, double-blind study. / Calabresi, Peter; Kieseier, Bernd C.; Arnold, Douglas L.; Balcer, Laura J.; Boyko, Alexey; Pelletier, Jean; Liu, Shifang; Zhu, Ying; Seddighzadeh, Ali; Hung, Serena; Deykin, Aaron.

In: The Lancet Neurology, Vol. 13, No. 7, 2014, p. 657-665.

Research output: Contribution to journalArticle

Calabresi, P, Kieseier, BC, Arnold, DL, Balcer, LJ, Boyko, A, Pelletier, J, Liu, S, Zhu, Y, Seddighzadeh, A, Hung, S & Deykin, A 2014, 'Pegylated interferon beta-1a for relapsing-remitting multiple sclerosis (ADVANCE): A randomised, phase 3, double-blind study', The Lancet Neurology, vol. 13, no. 7, pp. 657-665. https://doi.org/10.1016/S1474-4422(14)70068-7
Calabresi, Peter ; Kieseier, Bernd C. ; Arnold, Douglas L. ; Balcer, Laura J. ; Boyko, Alexey ; Pelletier, Jean ; Liu, Shifang ; Zhu, Ying ; Seddighzadeh, Ali ; Hung, Serena ; Deykin, Aaron. / Pegylated interferon beta-1a for relapsing-remitting multiple sclerosis (ADVANCE) : A randomised, phase 3, double-blind study. In: The Lancet Neurology. 2014 ; Vol. 13, No. 7. pp. 657-665.
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title = "Pegylated interferon beta-1a for relapsing-remitting multiple sclerosis (ADVANCE): A randomised, phase 3, double-blind study",
abstract = "Background: Subcutaneous pegylated interferon (peginterferon) beta-1a is being developed for treatment of relapsing multiple sclerosis, with less frequent dosing than currently available first-line injectable treatments. We assessed the safety and efficacy of peginterferon beta-1a after 48 weeks of treatment in the placebo-controlled phase of the ADVANCE trial, a study of patients with relapsing-remitting multiple sclerosis. Methods: We did this 2-year, double-blind, parallel group, phase 3 study, with a placebo-controlled design for the first 48 weeks, at 183 sites in 26 countries. Patients with relapsing-remitting multiple sclerosis (age 18-65 years, with Expanded Disability Status Scale score ≤5) were randomly assigned (1:1:1) via an interactive voice response or web system, and stratified by site, to placebo or subcutaneous peginterferon beta-1a 125 μg once every 2 weeks or every 4 weeks. The primary endpoint was annualised relapse rate at 48 weeks. This trial is registered with ClinicalTrials.gov, number NCT00906399. Findings: We screened 1936 patients and enrolled 1516, of whom 1512 were randomly assigned (500 to placebo, 512 to peginterferon every 2 weeks, 500 to peginterferon every 4 weeks); 1332 (88{\%}) patients completed 48 weeks of treatment. Adjusted annualised relapse rates were 0·397 (95{\%} CI 0·328-0·481) in the placebo group versus 0·256 (0·206-0·318) in the every 2 weeks group and 0·288 (0·234-0·355) in the every 4 weeks group (rate ratio for every 2 weeks group 0·644, 95{\%} CI 0·500-0·831, p=0·0007; rate ratio for the every 4 weeks group 0·725, 95{\%} CI 0·565-0·930, p=0·0114). 417 (83{\%}) patients taking placebo, 481 (94{\%}) patients taking peginterferon every 2 weeks, and 472 (94{\%}) patients taking peginterferon every 4 weeks reported adverse events including relapses. The most common adverse events associated with peginterferon beta-1a were injection site reactions, influenza-like symptoms, pyrexia, and headache. 76 (15{\%}) patients taking placebo, 55 (11{\%}) patients taking study drug every 2 weeks, and 71 (14{\%}) patients taking study drug every 4 weeks reported serious adverse events; relapse, pneumonia, and urinary tract infection were the most common. Interpretation: After 48 weeks, peginterferon beta-1a significantly reduced relapse rate compared with placebo. The drug might be an effective treatment for relapsing-remitting multiple sclerosis with less frequent administration than available treatments. Funding: Biogen Idec.",
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T1 - Pegylated interferon beta-1a for relapsing-remitting multiple sclerosis (ADVANCE)

T2 - A randomised, phase 3, double-blind study

AU - Calabresi, Peter

AU - Kieseier, Bernd C.

AU - Arnold, Douglas L.

AU - Balcer, Laura J.

AU - Boyko, Alexey

AU - Pelletier, Jean

AU - Liu, Shifang

AU - Zhu, Ying

AU - Seddighzadeh, Ali

AU - Hung, Serena

AU - Deykin, Aaron

PY - 2014

Y1 - 2014

N2 - Background: Subcutaneous pegylated interferon (peginterferon) beta-1a is being developed for treatment of relapsing multiple sclerosis, with less frequent dosing than currently available first-line injectable treatments. We assessed the safety and efficacy of peginterferon beta-1a after 48 weeks of treatment in the placebo-controlled phase of the ADVANCE trial, a study of patients with relapsing-remitting multiple sclerosis. Methods: We did this 2-year, double-blind, parallel group, phase 3 study, with a placebo-controlled design for the first 48 weeks, at 183 sites in 26 countries. Patients with relapsing-remitting multiple sclerosis (age 18-65 years, with Expanded Disability Status Scale score ≤5) were randomly assigned (1:1:1) via an interactive voice response or web system, and stratified by site, to placebo or subcutaneous peginterferon beta-1a 125 μg once every 2 weeks or every 4 weeks. The primary endpoint was annualised relapse rate at 48 weeks. This trial is registered with ClinicalTrials.gov, number NCT00906399. Findings: We screened 1936 patients and enrolled 1516, of whom 1512 were randomly assigned (500 to placebo, 512 to peginterferon every 2 weeks, 500 to peginterferon every 4 weeks); 1332 (88%) patients completed 48 weeks of treatment. Adjusted annualised relapse rates were 0·397 (95% CI 0·328-0·481) in the placebo group versus 0·256 (0·206-0·318) in the every 2 weeks group and 0·288 (0·234-0·355) in the every 4 weeks group (rate ratio for every 2 weeks group 0·644, 95% CI 0·500-0·831, p=0·0007; rate ratio for the every 4 weeks group 0·725, 95% CI 0·565-0·930, p=0·0114). 417 (83%) patients taking placebo, 481 (94%) patients taking peginterferon every 2 weeks, and 472 (94%) patients taking peginterferon every 4 weeks reported adverse events including relapses. The most common adverse events associated with peginterferon beta-1a were injection site reactions, influenza-like symptoms, pyrexia, and headache. 76 (15%) patients taking placebo, 55 (11%) patients taking study drug every 2 weeks, and 71 (14%) patients taking study drug every 4 weeks reported serious adverse events; relapse, pneumonia, and urinary tract infection were the most common. Interpretation: After 48 weeks, peginterferon beta-1a significantly reduced relapse rate compared with placebo. The drug might be an effective treatment for relapsing-remitting multiple sclerosis with less frequent administration than available treatments. Funding: Biogen Idec.

AB - Background: Subcutaneous pegylated interferon (peginterferon) beta-1a is being developed for treatment of relapsing multiple sclerosis, with less frequent dosing than currently available first-line injectable treatments. We assessed the safety and efficacy of peginterferon beta-1a after 48 weeks of treatment in the placebo-controlled phase of the ADVANCE trial, a study of patients with relapsing-remitting multiple sclerosis. Methods: We did this 2-year, double-blind, parallel group, phase 3 study, with a placebo-controlled design for the first 48 weeks, at 183 sites in 26 countries. Patients with relapsing-remitting multiple sclerosis (age 18-65 years, with Expanded Disability Status Scale score ≤5) were randomly assigned (1:1:1) via an interactive voice response or web system, and stratified by site, to placebo or subcutaneous peginterferon beta-1a 125 μg once every 2 weeks or every 4 weeks. The primary endpoint was annualised relapse rate at 48 weeks. This trial is registered with ClinicalTrials.gov, number NCT00906399. Findings: We screened 1936 patients and enrolled 1516, of whom 1512 were randomly assigned (500 to placebo, 512 to peginterferon every 2 weeks, 500 to peginterferon every 4 weeks); 1332 (88%) patients completed 48 weeks of treatment. Adjusted annualised relapse rates were 0·397 (95% CI 0·328-0·481) in the placebo group versus 0·256 (0·206-0·318) in the every 2 weeks group and 0·288 (0·234-0·355) in the every 4 weeks group (rate ratio for every 2 weeks group 0·644, 95% CI 0·500-0·831, p=0·0007; rate ratio for the every 4 weeks group 0·725, 95% CI 0·565-0·930, p=0·0114). 417 (83%) patients taking placebo, 481 (94%) patients taking peginterferon every 2 weeks, and 472 (94%) patients taking peginterferon every 4 weeks reported adverse events including relapses. The most common adverse events associated with peginterferon beta-1a were injection site reactions, influenza-like symptoms, pyrexia, and headache. 76 (15%) patients taking placebo, 55 (11%) patients taking study drug every 2 weeks, and 71 (14%) patients taking study drug every 4 weeks reported serious adverse events; relapse, pneumonia, and urinary tract infection were the most common. Interpretation: After 48 weeks, peginterferon beta-1a significantly reduced relapse rate compared with placebo. The drug might be an effective treatment for relapsing-remitting multiple sclerosis with less frequent administration than available treatments. Funding: Biogen Idec.

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