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Natalizumab: A Review of Its Use in the Management of Relapsing-Remitting Multiple Sclerosis

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Abstract

Natalizumab (Tysabri®) is a humanized monoclonal antibody against the α4 chain of integrins and was the first targeted therapy to be approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Natalizumab acts as a selective adhesion molecule antagonist, which binds very late antigen (VLA)-4 and inhibits the translocation of activated VLA-4-expressing leukocytes across the blood–brain barrier into the CNS. In a pivotal phase III clinical trial, natalizumab 300 mg intravenously every 4 weeks for 2 years in adults with RRMS significantly reduced the annualized relapse rate and the risk of sustained progression of disability compared with placebo, as well as significantly increasing the proportion of relapse-free patients at 1 and 2 years. Natalizumab also significantly reduced the number of T2-hyperintense, gadolinium-enhancing and T1-hypointense lesions on magnetic resonance imaging, and significantly reduced the volume of T2-hyperintense and T1-hypointense lesions compared with placebo. Natalizumab recipients generally experienced improved health-related quality of life at 1–2 years. Natalizumab was generally well tolerated in pivotal trials. The only adverse events that were more frequent with natalizumab monotherapy than with placebo were fatigue and allergic reactions. The main safety and tolerability issue with natalizumab is the incidence of progressive multifocal leukoencephalopathy (PML). As long as the risk of PML is managed effectively, natalizumab is a valuable therapeutic option for adults with highly active relapsing forms of multiple sclerosis.

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The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

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    Paul L. McCormack

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Correspondence to Paul L. McCormack.

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The manuscript was reviewed by: A. Chaudhuri, Department of Neurology, Queen’s Hospital, Romford, London, UK; O. Fernández, Service of Neurology, Institute of Neurosciences, Hospital Regional Universitario Carlos Haya, Malaga, Spain; H. Lassmann, Center for Brain Research, Medical University of Vienna, Vienna, Austria; T. Menge, Department of Neurology, Heinrich-Heine University, Düsseldorf, Germany; F. Piehl, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; W.A. Sheremata, Department of Neurology, Multiple Sclerosis Center of Excellence, Miller School of Medicine, University of Miami, Miami, FL, USA.

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McCormack, P.L. Natalizumab: A Review of Its Use in the Management of Relapsing-Remitting Multiple Sclerosis. Drugs 73, 1463–1481 (2013). https://doi.org/10.1007/s40265-013-0102-7

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  • DOI: https://doi.org/10.1007/s40265-013-0102-7

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