First-line natalizumab in multiple sclerosis: rationale, patient selection, benefits and risks

Natalizumab (NTZ) is a highly effective disease modifying therapy for the treatment of relapsing forms of multiple sclerosis (MS). Despite evidence to support its use as first-line therapy, risk of NTZ-associated progressive multifocal leukoencephalopathy (PML) has largely contributed to it being relegated to a second-line position. Recent preliminary data may allow for a more accurate analysis of JC virus (JCV) risk stratification of a given patient's PML risk. Herein we propose an algorithm to help guide clinicians through this decision-making process. We recommend that NTZ be considered for first-line use in JCV antibody negative MS patients, JCV 'low positive' MS patients without prior exposure to immunosuppression and for a limited period (12-24 months) in JCV 'high positive' MS patients with an aggressive disease course. We caution against first-line use in JCV antibody 'high positive' patients beyond 12-24 months and any JCV antibody positive patient with a history of prior immunosuppression.