Natalizumab dosage suspension: Are we helping or hurting?

The risk of developing progressive multifocal leukoencephalopathy increases with the duration of treatment with natalizumab. Planned dosage interruptions have been proposed as a means of decreasing cumulative risk. The clinical consequences of dosage interruption were evaluated in a single center cohort of natalizumab‐treated patients. Medical records were reviewed for 84 patients identified with multiple sclerosis who received 12 or more infusions of natalizumab at an academic multiple sclerosis center. Eighty‐one percent (68/84) underwent a dosage interruption, and 19% (16/84) had no interruption in natalizumab treatment. Of those with a treatment interruption, 27.9% (19/68) experienced a clinical relapse within 6 months of the suspension, whereas none of the patients with ongoing treatment experienced a flare during months 12 to 18 of treatment ( p = 0.017, Fisher exact test). Survival analysis showed that Kaplan‐Meier curves comparing dosage interruption to ongoing treatment diverged ( p = 0.025). Median time from treatment interruption to relapse onset was 3 months. No clinical predictors associated with an increased risk of developing flares during dosage interruption were identified. Among the 19 patients who had a flare, 7 had severe flares, with a mean number of 16 Gad+ lesions on brain magnetic resonance imaging (range, 6–40). Their median Expanded Disability Status Scale at natalizumab interruption was 3.0 and increased to 6.0 during the flare ( p = 0.0008). Natalizumab dosage interruption is associated with clinical flares and return of radiographic inflammatory disease activity. Some of these flares can be clinically severe, with a high number of contrast‐enhanced lesions, suggesting a possible rebound of disease activity. Ann Neurol 2010;68:395–399