title: Natalizumab for the treatment of relapsing multiple sclerosis.
abstract: Natalizumab is an alpha4-integrin antagonist approved as monotherapy for patients with relapsing multiple sclerosis (MS), based on demonstrated efficacy in the pivotal AFFIRM study (N = 942). Natalizumab monotherapy reduced risk of disability progression by 42%-54% and annualized relapse rate by 68% during a period of 2 years. Natalizumab was also associated with significant reductions in number of T2-hyperintense, gadolinium-enhancing, and T1-hypointense lesions and in volume of T2-hyperintense lesions (all p < 0.001) on magnetic resonance imaging. Furthermore, natalizumab-treated patients in AFFIRM experienced significant improvements from baseline in the physical and mental components of the Short Form-36 (p </= 0.01) and a 35% reduction in risk of clinically significant vision loss (p = 0.008 vs placebo). Natalizumab was well tolerated in phase 3 studies. Common adverse events were generally mild and included headache, fatigue, urinary tract infections, and arthralgia. Serious adverse events were similar between treatment groups. The incidence of serious hypersensitivity reactions associated with natalizumab was <1%. Progressive multifocal leukoencephalopathy was a rare complication of treatment, observed in 2 patients with MS who received natalizumab plus interferon beta-1a. The robust clinical benefits of natalizumab, including benefits on patient-reported quality of life, make it an important addition to disease-modifying therapies available to patients with relapsing MS.
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH, USA;
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rudick
authors.forename: Michael A
authors.initials: MA
authors.lastname: Panzara
references.citation: Lancet Neurol. 2007 May;6(5):431-41
references.pmid: 17434098
references.citation: Neurology. 2007 Oct 2;69(14):1391-403
references.pmid: 17761550
references.citation: Neurology. 1999 Nov 10;53(8):1698-704
references.pmid: 10563615
references.citation: Neurology. 2007 Apr 17;68(16):1299-304
references.pmid: 17438220
references.citation: J Neuroimmunol. 2007 Jul;187(1-2):156-8
references.pmid: 17499366
references.citation: Ann Neurol. 1997 Sep;42(3):379-82
references.pmid: 9307263
references.citation: Neurology. 1995 Jul;45(7):1268-76
references.pmid: 7617181
references.citation: Ann Neurol. 1996 Mar;39(3):285-94
references.pmid: 8602746
references.citation: N Engl J Med. 2000 Sep 28;343(13):938-52
references.pmid: 11006371
references.citation: Neurology. 1999 Feb;52(3):623-5
references.pmid: 10025799
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: Neurology. 1996 Apr;46(4):907-11
references.pmid: 8780061
references.citation: N Engl J Med. 2005 Jul 28;353(4):362-8
references.pmid: 15947080
references.citation: Lancet. 1994 Jan 29;343(8892):271-5
references.pmid: 7905102
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: Ann Neurol. 2007 Oct;62(4):335-46
references.pmid: 17696126
references.citation: J Neurol. 2004 Jun;251 Suppl 2:II4-9
references.pmid: 15264106
references.citation: Ann Neurol. 2001 Jul;50(1):121-7
references.pmid: 11456302
references.citation: Neurology. 2007 Apr 24;68(17):1390-401
references.pmid: 17452584
references.citation: N Engl J Med. 2006 Mar 2;354(9):899-910
references.pmid: 16510744
references.citation: Med Care. 1992 Jun;30(6):473-83
references.pmid: 1593914
references.citation: N Engl J Med. 2005 Jul 28;353(4):375-81
references.pmid: 15947078
references.citation: Transpl Int. 2005 Jan;17(11):658-65
references.pmid: 15616809
references.citation: Clin Microbiol Rev. 1992 Jan;5(1):49-73
references.pmid: 1310438
references.citation: Lancet. 1998 Nov 7;352(9139):1498-504
references.pmid: 9820297
references.citation: Am J Transplant. 2005 May;5(5):1151-8
references.pmid: 15816900