Natalizumab plus Interferon Beta-1a for Relapsing Multiple Sclerosis

• Published in: The New England journal of medicine Vol. 354; no. 9; pp. 911 - 923
• Main Authors: Rudick, Richard A, Stuart, William H, Calabresi, Peter A, Confavreux, Christian, Galetta, Steven L, Radue, Ernst-Wilhelm, Lublin, Fred D, Weinstock-Guttman, Bianca, Wynn, Daniel R, Lynn, Frances, Panzara, Michael A, Sandrock, Alfred W
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 02-03-2006
• Subjects: Adolescent; Adult; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Brain - pathology; Cell Adhesion Molecules - antagonists & inhibitors; Clinical trials; Disease Progression; Drug therapy; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Integrin alpha4; Interferon; Interferon beta-1a; Interferon-beta - adverse effects; Interferon-beta - therapeutic use; JC Virus; Leukoencephalopathy, Progressive Multifocal - chemically induced; Male; Middle Aged; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - pathology; Natalizumab; Proportional Hazards Models; Secondary Prevention
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa044396

In this randomized trial involving patients with relapsing multiple sclerosis who had had relapses despite treatment with interferon, natalizumab in combination with interferon was more effective than interferon alone. After two years, the probability of sustained disability progression was 23 percent with combination treatment and 29 percent with interferon alone. Progressive multifocal leukoencephalopathy developed in two patients receiving combination treatment, and one of these two patients died of this serious complication of therapy.
The adhesion molecule α
4
β
1
integrin is a key initiator of the inflammatory cascade involved in the pathogenesis of multiple sclerosis.
1
–
4
Natalizumab (Tysabri, Biogen Idec and Elan Pharmaceuticals) is the first α
4
integrin antagonist in a new class of selective adhesion-molecule inhibitors for the treatment of multiple sclerosis. Natalizumab binds to α
4
integrin on the surface of leukocytes, inhibiting their migration into the brain and thereby reducing inflammation.
Current disease-modifying therapies for relapsing–remitting multiple sclerosis (interferon beta and glatiramer acetate) are only partially effective,
5
–
8
and most patients with multiple sclerosis have breakthrough disease activity . . .