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Interferon-beta

Mechanism of action and dosing issues

From the Multiple Sclerosis Center, University of Pennsylvania, Philadelphia, Pennsylvania.

Address correspondence and reprint requests to Dr. Clyde E. Markowitz, Multiple Sclerosis Center, University of Pennsylvania, Three West Gates Building, 3400 Spruce Street, Philadelphia, PA 19104 cmarkowi{at}mail.med.upenn.edu

In patients with multiple sclerosis (MS), activation of immune cells and breakdown of the blood–brain barrier (BBB) lead to demyelination and axon injury. Although repairing damage to neurons is not possible, immunomodulating therapies can reduce the inflammatory processes that lead to demyelination. Interferon-beta (IFN-ß) is a polypeptide, normally produced by fibroblasts, that has antiviral and antiproliferative effects. Binding of IFN-ß to its receptor induces a complex transcriptional response. In immune cells (the most likely target of IFN-ß’s therapeutic effect in MS), IFN-ß reduces antigen presentation and T-cell proliferation, alters cytokine and matrix metalloproteinase (MMP) expression, and restores suppressor function. Therapeutic forms of IFN-ß can be produced in bacterial expression systems (IFN-ß1b) or in mammalian cells (IFN-ß1a). These forms have some differences in their amino acid sequence and posttranslational modifications, but the transcriptional response to IFN- ß1b and IFN-ß1a appears to be similar, if not indistinguishable. However, the biological response and the clinical effect do vary with changes in the dosing frequency of IFN-ß. In clinical trials, IFN-ß1a IM administered weekly elicits a transient biological response compared to IFN-ß1b administered SC every other day or IFN-ß1a (administered SC three times per week). Comparative clinical trials suggest that the differences in the biological response are clinically meaningful: more frequent IFN-ß administration produces superior clinical responses.

Disclosure: Dr. Markowitz receives research funding and/or honoraria from Berlex, Inc., Biogen Idec, Bristol-Myers Squibb Company, Genentech, Inc., Merck & Co., Inc., Neurocrine Biosciences, Inc., PDL BioPharma, Inc., Pfizer, Inc., Serono, Inc., Teva, and Wyeth Pharmaceuticals. Publication of this supplement was supported by an educational grant from Bayer HealthCare Pharmaceuticals Inc.

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