title: Natalizumab in the treatment of multiple sclerosis.
abstract: Natalizumab is a monoclonal antibody, representing a new class of medication for treating relapsing multiple sclerosis (MS). Conventional treatments include interferons, glatiramer acetate and chemotherapies such as mitoxantrone and cyclophosphamide. These therapies offer only modest clinical benefits and are commonly not tolerated due to side effects. Natalizumab has been proven in large-scale, blinded, randomized, controlled trials to have an exceptional effect on preventing relapses, decreasing the risk of sustained progression of disability, and increasing the rate of disease-free patients over a 24-month period compared to placebo. These trials led to the speedy approval of natalizumab for treating relapsing MS, but its use was halted a few months after its induction after several cases of progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease affecting the central nervous system. After a long deliberation by an FDA advisory panel and strong support from the MS community, natalizumab was reapproved with stringent restrictions including patient, provider and site registration. Natalizumab is now considered second-line therapy for patients who have failed first-line agents such as interferon or glatiramer acetate. As little is known about additional risk factors for PML and other potential infections, patients and providers must work together to carefully decide if potential benefits outweigh these rare but potentially devastating complications.
authors.affiliation: Department of Pharmacy, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Brandon A
authors.initials: BA
authors.lastname: Brown
references.citation: Arch Pathol Lab Med. 2008 Nov;132(11):1830-4
references.pmid: 18976024
references.citation: N Engl J Med. 2005 Jul 28;353(4):362-8
references.pmid: 15947080
references.citation: Curr Med Res Opin. 2008 Sep;24(9):2679-90
references.pmid: 18694542
references.citation: N Engl J Med. 2006 Mar 2;354(9):899-910
references.pmid: 16510744
references.citation: Ann Intern Med. 1987 Jul;107(1):78-87
references.pmid: 3296901
references.citation: N Engl J Med. 2005 Jul 28;353(4):375-81
references.pmid: 15947078
references.citation: Neurology. 2009 Feb 3;72(5):396-401
references.pmid: 18987352
references.citation: Neurol Clin. 2008 Aug;26(3):833-54, x-xi
references.pmid: 18657729
references.citation: J Neurol. 2008 Nov;255(11):1815-7
references.pmid: 19031099
references.citation: Neurology. 2008 Mar 25;70(13 Pt 2):1150-1
references.pmid: 17872364
references.citation: Ann Neurol. 2009 Sep;66(3):403-6
references.pmid: 19798640
references.citation: Neurology. 1993 Apr;43(4):655-61
references.pmid: 8469318
references.citation: N Engl J Med. 2006 Mar 2;354(9):911-23
references.pmid: 16510745
references.citation: Ann Neurol. 2005 Dec;58(6):840-6
references.pmid: 16283615
references.citation: N Engl J Med. 2007 Jun 21;356(25):2622-9
references.pmid: 17582072
references.citation: Ann Neurol. 2006 May;59(5):743-7
references.pmid: 16634029
references.citation: Neurology. 1999 Aug 11;53(3):466-72
references.pmid: 10449105
references.citation: N Engl J Med. 2005 Jul 28;353(4):369-74
references.pmid: 15947079
references.citation: N Engl J Med. 2006 Mar 2;354(9):924-33
references.pmid: 16510746
references.citation: Neurology. 1983 Nov;33(11):1444-52
references.pmid: 6685237
references.citation: Neurology. 2009 Feb 3;72(5):402-9
references.pmid: 19188571
references.citation: Arch Neurol. 2007 Sep;64(9):1331-3
references.pmid: 17846274
references.citation: Intervirology. 1997;40(2-3):98-111
references.pmid: 9450227
references.citation: Mult Scler. 2009 Apr;15(4):525-6
references.pmid: 19324985
references.citation: Neurology. 2006 Sep 12;67(5):884-6
references.pmid: 16966559
references.citation: N Engl J Med. 2008 Feb 7;358(6):647-8
references.pmid: 18256405
references.citation: Curr Opin Neurol. 2004 Jun;17(3):365-70
references.pmid: 15167073
references.citation: N Engl J Med. 1983 Jan 27;308(4):173-80
references.pmid: 6294517
references.citation: Eur Arch Psychiatry Clin Neurosci. 1992;242(2-3):96-102
references.pmid: 1486115
references.citation: Arch Neurol. 2008 May;65(5):656-8
references.pmid: 18474743
references.citation: N Engl J Med. 1998 May 7;338(19):1345-51
references.pmid: 9571254
references.citation: Science. 2004 Nov 19;306(5700):1380-3
references.pmid: 15550673
references.citation: Arch Neurol. 2009 Feb;66(2):255-8
references.pmid: 19204164