A review of the evidence for a natalizumab exit strategy for patients with multiple sclerosis.

Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis (RRMS), but treatment for >2 years is associated with an increased risk of opportunistic infection and progressive multifocal leukoencephalopathy (PML). For this reason, patients and physicians may consider discontinuing natalizumab therapy. This article reviews the evidence for the various therapeutic approaches that may be taken in such patients. Stopping therapy altogether is unlikely to be appropriate for most patients, as it is associated with a high rate of relapse or rebound. Continuing natalizumab therapy with increased monitoring and vigilance for PML may be an acceptable option for some patients, while the data on extending the dosing interval of natalizumab look promising. In some patients whose pre-natalizumab disease activity was not very high and who did not relapse while on natalizumab, switching to a first-line treatment may be an option. In this case, dimethyl fumarate may carry a lower risk of relapse than interferon beta or glatiramer acetate. Fingolimod is the most studied post-natalizumab therapy, and the relapse rate appears to be higher than on natalizumab but lower than was seen before initiation of natalizumab. The evidence suggests that the washout period between natalizumab and fingolimod should not exceed 12 weeks. Finally, the limited evidence available for rituximab and alemtuzumab is promising, and further data on these and other newer therapies for RRMS are awaited.