Treating multiple sclerosis in the natalizumab era: risks, benefits, clinical decision making, and a comparison between North American and European Union practices.

Multiple sclerosis (MS) is the most common cause of nontraumatic severe neurological disability in young adults. If left untreated, most individuals with MS will accumulate significant physical and/or cognitive disability as the consequence of demyelination and axonal injury. Treatment has focused on disease-modifying therapies (DMTs) and questions remain about timing and indications for their use. Natalizumab is a humanized monoclonal antibody directed against alpha4-integrin that prevents migration of leukocytes into the brain parenchyma. The clinical and radiological efficacy of natalizumab has been shown in several randomized trials; however, adverse events associated with natalizumab have limited its use as a first-line agent. In this review we compare current recommendations for the use of first-line DMTs, adverse events associated with MS therapies, and differences between the practices in North American and the European Union.