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Natalizumab.

Abstract
Medical therapeutics has entered a new and exciting era with the development of biological agents that target specific sites. In the studies performed to date, natalizumab, a humanized monoclonal antibody to alpha4 integrin, when administered intravenously at monthly intervals, appeared to be highly beneficial with respect to decreasing both relapse rate and contrast-enhancing lesions in multiple sclerosis. Salutary actions on other disease parameters were also observed. However, treatment with natalizumab was complicated by the development of a rare demyelinating disease of the brain--progressive multifocal leukoencephalopathy (PML)--that developed in three patients in clinical trials of the drug. Currently, the estimated incidence for the development of PML with natalizumab treatment is 1:1,000 after approximately 18 months of therapy; however, as the development of PML is a stochastic event, it is quite possible that higher rates will be observed after longer treatment courses. Curiously, other opportunistic infections were not observed at higher rates in the treated groups when compared to controls, suggesting a specific association between natalizumab, and perhaps other alpha4 integrin blockers, and PML. Postmarketing surveillance studies should answer this and other questions related to the use of natalizumab.
AuthorsJoseph R Berger
JournalDrugs of today (Barcelona, Spain : 1998) (Drugs Today (Barc)) Vol. 42 Issue 10 Pg. 639-55 (Oct 2006) ISSN: 1699-3993 [Print] Spain
PMID17136224 (Publication Type: Journal Article, Review)
CopyrightCopyright 2006 Prous Science.All rights reserved.
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Natalizumab
  • Integrin alpha4
Topics
  • Antibodies, Monoclonal (adverse effects, immunology, therapeutic use)
  • Antibodies, Monoclonal, Humanized
  • Humans
  • Integrin alpha4 (immunology)
  • Leukoencephalopathy, Progressive Multifocal (chemically induced, diagnosis)
  • Magnetic Resonance Imaging
  • Models, Biological
  • Multiple Sclerosis (drug therapy)
  • Natalizumab

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