title: Natalizumab dosage suspension: are we helping or hurting?
abstract: 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.
authors.affiliation: Multiple Sclerosis Center, University of California at San Francisco, San Francisco, CA, USA. Timothy.West@ucsf.edu
authors.forename: Timothy W
authors.initials: TW
authors.lastname: West
authors.forename: Bruce A C
authors.initials: BA
authors.lastname: Cree
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001921:Brain / Q000473:pathology; D016009:Chi-Square Distribution; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D039441:Integrin alpha4 / Q000276:immunology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology; D000069442:Natalizumab; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab; D039441:Integrin alpha4