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 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 "Disease-modifying 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].
Natalizumab is one of several disease-modifying agents that effectively reduce the relapse rate for patients with relapsing-remitting multiple sclerosis (RRMS). The main concern with natalizumab therapy is the risk of developing progressive multifocal leukoencephalopathy (PML). The choice of a specific agent for patients with RRMS should be individualized according to disease activity and patient values and preferences (algorithm 1), as discussed in detail elsewhere (see "Disease-modifying treatment of relapsing-remitting multiple sclerosis in adults"). In this context, we suggest infusion therapy with natalizumab for patients with more active RRMS and for those who value effectiveness above safety and convenience, including use of natalizumab as a first-line agent. In contrast, earlier guidelines (published in 2008) by the American Academy of Neurology (AAN) recommended that natalizumab be reserved for patients with RRMS who failed other therapies because of continued disease activity or medication intolerance, or who had a very aggressive initial disease course . (See "Disease-modifying treatment of relapsing-remitting multiple sclerosis in adults", section on 'Refractory disease'.)
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