See the Appendix on page 12.
Randomized study combining interferon and glatiramer acetate in multiple sclerosis
Article first published online: 11 MAR 2013
Copyright © 2013 American Neurological Association
Annals of Neurology
Volume 73, Issue 3, pages 327–340, March 2013
How to Cite
Lublin, F. D., Cofield, S. S., Cutter, G. R., Conwit, R., Narayana, P. A., Nelson, F., Salter, A. R., Gustafson, T., Wolinsky, J. S. and for the CombiRx Investigators (2013), Randomized study combining interferon and glatiramer acetate in multiple sclerosis. Ann Neurol., 73: 327–340. doi: 10.1002/ana.23863
- Issue published online: 17 APR 2013
- Article first published online: 11 MAR 2013
- Accepted manuscript online: 19 FEB 2013 09:42AM EST
- Manuscript Accepted: 1 FEB 2013
- Manuscript Revised: 30 JAN 2013
- Manuscript Received: 6 DEC 2012
- National Institute of Neurological Disorders. Grant Numbers: UO1NS045719, R21NS41986, 2RO1-EB002095-06A1, NCT00211887
A double-blind, randomized, controlled study was undertaken to determine whether combined use of interferon β-1a (IFN) 30μg intramuscularly weekly and glatiramer acetate (GA) 20mg daily is more efficacious than either agent alone in relapsing–remitting multiple sclerosis.
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.
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.
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. ANN NEUROL 2013;73:327–340