OBJECTIVE: A double-blind, randomized, controlled study was undertaken to determine whether combined use of interferon β-1a (IFN) 30 μg intramuscularly weekly and glatiramer acetate (GA) 20 mg daily is more efficacious than either agent alone in relapsing-remitting multiple sclerosis. METHODS:A total of 1,008 participants were randomized and followed until the last participant enrolled completed 3 years. The primary endpoint was reduction in annualized relapse rate utilizing a strict definition of relapse. Secondary outcomes included time to confirmed disability, Multiple Sclerosis Functional Composite (MSFC) score, and magnetic resonance imaging (MRI) metrics. RESULTS:Combination IFN+GA was not superior to the better of the single agents (GA) in risk of relapse. Both the combination therapy and GA were significantly better than IFN in reducing the risk of relapse. The combination was not better than either agent alone in lessening confirmed Expanded Disability Status Scale progression or change in MSFC over 36 months. The combination was superior to either agent alone in reducing new lesion activity and accumulation of total lesion volumes. In a post hoc analysis, combination therapy resulted in a higher proportion of participants attaining disease activity-free status (DAFS) compared to either single arm, driven by the MRI results. INTERPRETATION: Combining the 2 most commonly prescribed therapies for multiple sclerosis did not produce a significant clinical benefit over 3 years. An effect was seen on some MRI metrics. In a test of comparative efficacy, GA was superior to IFN in reducing the risk of exacerbation. The extension phase for CombiRx will address whether the observed differences in MRI and DAFS findings predict later clinical differences.
RCT Entities:
OBJECTIVE: A double-blind, randomized, controlled study was undertaken to determine whether combined use of interferon β-1a (IFN) 30 μg intramuscularly weekly and glatiramer acetate (GA) 20 mg daily is more efficacious than either agent alone in relapsing-remitting multiple sclerosis. METHODS: A total of 1,008 participants were randomized and followed until the last participant enrolled completed 3 years. The primary endpoint was reduction in annualized relapse rate utilizing a strict definition of relapse. Secondary outcomes included time to confirmed disability, Multiple Sclerosis Functional Composite (MSFC) score, and magnetic resonance imaging (MRI) metrics. RESULTS: Combination IFN+GA was not superior to the better of the single agents (GA) in risk of relapse. Both the combination therapy and GA were significantly better than IFN in reducing the risk of relapse. The combination was not better than either agent alone in lessening confirmed Expanded Disability Status Scale progression or change in MSFC over 36 months. The combination was superior to either agent alone in reducing new lesion activity and accumulation of total lesion volumes. In a post hoc analysis, combination therapy resulted in a higher proportion of participants attaining disease activity-free status (DAFS) compared to either single arm, driven by the MRI results. INTERPRETATION: Combining the 2 most commonly prescribed therapies for multiple sclerosis did not produce a significant clinical benefit over 3 years. An effect was seen on some MRI metrics. In a test of comparative efficacy, GA was superior to IFN in reducing the risk of exacerbation. The extension phase for CombiRx will address whether the observed differences in MRI and DAFS findings predict later clinical differences.
Authors: J S Wolinsky; P A Narayana; J H Noseworthy; F D Lublin; J N Whitaker; A Linde; P Gjörstrup; H C Sullivan Journal: Neurology Date: 2000-05-09 Impact factor: 9.910
Authors: Axel Petzold; Tjeerd Mondria; Jens Kuhle; Maria A Rocca; Jan Cornelissen; Peter te Boekhorst; Bob Lowenberg; Gavin Giovannoni; Massimo Filippi; Ludwig Kappos; Rogier Hintzen Journal: Ann Neurol Date: 2010-12 Impact factor: 10.422
Authors: Paul O'Connor; Jerry S Wolinsky; Christian Confavreux; Giancarlo Comi; Ludwig Kappos; Tomas P Olsson; Hadj Benzerdjeb; Philippe Truffinet; Lin Wang; Aaron Miller; Mark S Freedman Journal: N Engl J Med Date: 2011-10-06 Impact factor: 91.245
Authors: W I McDonald; A Compston; G Edan; D Goodkin; H P Hartung; F D Lublin; H F McFarland; D W Paty; C H Polman; S C Reingold; M Sandberg-Wollheim; W Sibley; A Thompson; S van den Noort; B Y Weinshenker; J S Wolinsky Journal: Ann Neurol Date: 2001-07 Impact factor: 10.422
Authors: Minal J Bhanushali; Tarah Gustafson; Steve Powell; Robin A Conwit; Jerry S Wolinsky; Gary R Cutter; Fred D Lublin; Stacey S Cofield Journal: Clin Trials Date: 2014-04 Impact factor: 2.486
Authors: Bonaventura Casanova; Laura Lacruz; María Luisa Villar; José Andrés Domínguez; María Carcelén Gadea; Francisco Gascón; Javier Mallada; David Hervás; María Simó-Castelló; José Carlos Álvarez-Cermeño; Carmen Calles; Javier Olascoaga; Lluís Ramió-Torrentà; Carmen Alcalá; Angeles Cervelló; Isabel Boscá; Francisco Carlos Pérez-Mirallles; Francisco Coret Journal: Neurol Sci Date: 2018-06-07 Impact factor: 3.307
Authors: Fred D Lublin; Stacey S Cofield; Gary R Cutter; Tarah Gustafson; Stephen Krieger; Ponnada A Narayana; Flavia Nelson; Amber R Salter; Jerry S Wolinsky Journal: Mult Scler Relat Disord Date: 2017-09-23 Impact factor: 4.339