Natalizumab (Tysabri) treatment for relapsing multiple sclerosis.
BACKGROUND
Natalizumab (Tysabri), a humanized monoclonal antibody which binds to the alpha4beta1 integrins of leukocytes, blocks attachment to cerebral endothelial cells, thus reducing inflammation at the blood-brain barrier. Two pivotal randomized trials, 1 comparing active treatment to placebo and 1 comparing active treatment to placebo in relapsing multiple sclerosis (MS) patients receiving intramuscular interferon beta1alpha (Avonex), demonstrated significant efficacy for relapse control, decrease in sustained disability, and reduced numbers of new lesions on MRI.


RESULTS
Because of safety issues raised by the appearance of 2 cases of progressive multifocal leukoencephalopathy in MS patients exposed to natalizumab for relapsing MS treatment has been restricted. This review briefly outlines the inflammatory nature of MS plagues, the mechanism of action of natalizumab and the pathogenesis of progressive multifocal leukoencephalopathy. The mandatory guidelines for natalizumab use in the treatment of MS with natalizumab are explained. Special concerns facing the therapist electing to prescribe natalizumab are mentioned.


CONCLUSIONS
Natalizumab recently joined glatiramer acetate and beta interferon as an approved therapy for controlling relapsing MS. Unresolved safety issues currently restrict its use to monotherapy in patients who have had inadequate response to the other immunomodulating agents.
Johnson
Kenneth P
KP
Department of Neurology, University of Maryland Baltimore School of Medicine, Maryland Center for Multiple Sclerosis, Baltimore, Maryland 21201, USA. kjohnson@som.umaryland.edu
D000911:Antibodies, Monoclonal / Q000266:history / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D049674:History, 21st Century; D006801:Humans; D039441:Integrin alpha4 / Q000276:immunology; D008279:Magnetic Resonance Imaging; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology; D000069442:Natalizumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab; D039441:Integrin alpha4