[Natalizumab in the treatment of multiple sclerosis].
OBJECTIVE
To review and update the mechanism of action of natalizumab and its efficacy in the treatment of multiple sclerosis (MS).


METHODS
Natalizumab, an anti-alfa-4 integrin monoclonal humanized antibody, binds to lymphocyte surface receptors to prevent transmigration of lymphocytes to areas of inflammation into the brain tissue. Furthermore, natalizumab appears to reduce T-cell activation following their infiltration of the brain parenchyma and may contribute to T-cell apoptosis in these tissues. Two large two-year, multicenter phase III trials (AFFIRM and SENTINEL) have been completed and demonstrate previously unseen efficacy in preventing MS relapses and disease progression. Natalizumab reduced the rate of clinical relapse at one year by 68 and 54% respectively in these trials (p < 0.001). Moreover, natalizumab reduced significantly the risk of sustained progression of disability by 42 and 24% respectively. Based on results from the AFFIRM study, the adverse events that were significantly more frequent in the natalizumab group than in the placebo group were fatigue (27 vs. 21%) and allergic reaction (9 vs. 4%). There was a low incidence (< 1%) of serious systemic hypersensitivity reactions described as anaphylactoid or anaphylactic, and they appear to be effectively managed by post-treatment observation and by timely and appropriate medical treatment. In the SENTINEL study, two cases of progressive multifocal leukoencephalopathy (PML), one of which was fatal, were diagnosed in natalizumab plus interferon beta-1a treated patients.


CONCLUSIONS
Natalizumab reduced the risk of the sustained progression of disability and the rate of clinical relapse in patients with relapsing MS. In spite of their low risk of adverse reactions, patients must be monitored at regular intervals for any new or worsening neurological symptoms or signs that may be suggestive of PML, and natalizumab use must be restricted to the indicated patients.
Horga
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Hospital General Universitario de Alicante, Servicio Neurologia, 03010 Alicante, Espana.
Horga de la Parte
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JF
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002986:Clinical Trials as Topic; D018450:Disease Progression; D006801:Humans; D039441:Integrin alpha4 / Q000378:metabolism; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000276:immunology / Q000627:therapeutic use; D007968:Leukoencephalopathy, Progressive Multifocal / Q000209:etiology / Q000276:immunology; D009103:Multiple Sclerosis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D000069442:Natalizumab; D012008:Recurrence; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab; D039441:Integrin alpha4; D016899:Interferon-beta; D000068556:Interferon beta-1a