Natalizumab for relapsing-remitting multiple sclerosis in adults
- Michael J Olek, DO
Michael J Olek, DO
- Associate Professor of Neurology
- Loma Linda University Medical Center
Natalizumab is an effective drug for the treatment of relapsing-remitting multiple sclerosis (RRMS). However, its use is rarely associated with the development of progressive multifocal leukoencephalopathy (PML), a potentially fatal complication.
This topic will review the use of natalizumab for the treatment of refractory or aggressive RRMS in adults. For initial disease modifying therapy of relapsing-remitting multiple sclerosis (RRMS), it is reasonable to begin treatment with interferon beta-1a, interferon beta-1b, or glatiramer acetate. These agents are discussed in detail separately. (See "Treatment of relapsing-remitting multiple sclerosis in adults".)
Natalizumab is a recombinant monoclonal antibody directed against alpha-4 integrins. The formation of inflammatory lesions in patients with multiple sclerosis (MS) may involve lymphocytes and monocytes that gain access to the brain parenchyma from the circulation by first adhering to vascular endothelial cells [1,2]. Alpha-4 integrin is expressed on the surface of inflammatory lymphocytes and monocytes and may play a critical role in their adhesion to the vascular endothelium.
Treatment with alpha-4 integrin antagonists in rodent models of MS led to reduced signs of disease activity and inflammation [3-5]. In a preliminary six-month clinical trial of 213 patients with MS, natalizumab treatment was associated with significantly fewer new enhancing brain lesions on MRI and significantly fewer relapses compared with placebo . In patients with MS, natalizumab treatment is associated with a diminished migratory capacity of immune cells and a prolonged decrease in lymphocyte counts in the cerebrospinal fluid [7,8].
In a 2011 systematic review of trials evaluating natalizumab for relapsing forms of multiple sclerosis (MS), pooled efficacy data from two randomized controlled trials, AFFIRM and SENTINEL, showed that natalizumab significantly reduced the risk for having a relapse during two years of treatment (relative risk [RR] 0.57, 95% CI 0.47-0.69) . In addition, natalizumab significantly reduced the risk for experiencing progression at two years (RR 0.74, 95% CI 0.62-0.89). The number needed to treat (NNT) to prevent one new exacerbation at two years was 4 (95% CI 3-5) and the NNT to prevent progression at two years was 10 (95% CI 7-23).
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