Clinical efficacy issues in the treatment of multiple sclerosis: update of natalizumab.

Multiple sclerosis is a frequent neurologic disease, which causes sensory impairment, fatigue, cognitive deficits, imbalance, loss of mobility, spasticity, and bladder and bowel dysfunction. Several new therapies have been introduced in the past decade, but additional drugs are needed to slow disease progression and reduce disability. Natalizumab (NA) is an α4 integrin antagonist, effective in decreasing the development of brain lesions in experimental models and in several studies of patients with MS. Six randomized controlled trials of NA in MS have been published in the last 10 years. Overall, 2,688 relapsing-remitting MS subjects have been enrolled in these studies. Hence, there are already sufficient data to draw some conclusions about the effectiveness of NA in the treatment of MS, although for definitive considerations it would be reasonable to wait for the observational phase IV studies of clinical practice to complete. Moreover, the medical community is concerned with the safety of NA, particularly with the risk of developing progressive multifocal leukoencephalopathy while on NA therapy. From the analyses of the six cases, it seems that the overall risk is around 1/1,000 and could increase with the number of NA infusions.