Natalizumab, a monoclonal antibody that blocks lymphocyte infiltration in the 
central nervous system, is a valuable tool in the treatment of relapsing forms 
of multiple sclerosis (MS). In a phase III clinical trial comparing natalizumab 
with placebo over 2 years, natalizumab reduced annualized relapse rate by 68%, 
12-week confirmed disability progression by 42%, and reduced contrast-enhancing 
lesions by 92%. In post hoc analyses, natalizumab treatment was associated with 
37% of patients achieving no evidence of disease activity (versus 7% on placebo) 
and 30% achieving sustained disability improvement (versus 19% on placebo). 
Natalizumab did not achieve a statistically significant primary composite 
disability outcome in a trial of 887 patients with secondary progressive MS, but 
it did demonstrate a benefit on a prespecified component of the 9-Hole Peg Test. 
The greatest risk of natalizumab treatment is progressive multifocal 
leukoencephalopathy (PML), with a 23% mortality rate. Risk stratification on the 
basis of immunosuppressant exposure, natalizumab treatment duration and 
anti-John Cunningham virus (JCV) antibody status and index has greatly improved 
clinical decision making. Other potential serious natalizumab-associated risks 
reported in clinical trials and postmarketing settings include infusion 
reactions, hepatotoxicity and rare, serious opportunistic infections. With more 
than a decade of continuous postmarketing experience, natalizumab remains a very 
effective option for patients with relapsing forms of MS. To optimize 
appropriate selection of natalizumab for patients with relapsing MS, however, a 
thorough understanding of individual patient risk factors for PML or other 
adverse events is also required.