title: Recurrence or rebound of clinical relapses after discontinuation of natalizumab therapy in highly active MS patients.
abstract: A number of studies have reported flare-up of multiple sclerosis (MS) disease activity after cessation of natalizumab, increasing to a level beyond the pre-natalizumab treatment level. Our aim was to describe the development in clinical disease activity following cessation of natalizumab therapy in a large unselected cohort of highly active patients. We studied 375 highly active patients who had suffered at least two significant relapses within 1 year or three relapses within 2 years, or had been treated with mitoxantrone for highly active disease. All patients had discontinued therapy with natalizumab after at least 24 weeks on therapy, and had been followed 3-12 months (mean 8.9 months) after cessation of natalizumab therapy. The annualised relapse rate before start of natalizumab therapy was 0.94 (95 % confidence interval [CI] 0.88-1.00), 0.47 (95 % CI 0.43-0.52) during natalizumab therapy, 0.63 (95 % CI 0.51-0.76) 1-6 months after natalizumab and 0.55 (95 % CI 0.42-0.70) 7-12 months after natalizumab. However, 83 (22 %) of the patients could be classified as showing rebound of relapses, defined as a higher individual relapse rate after cessation of natalizumab than before natalizumab. These patients had a higher annualised relapse rate during natalizumab therapy. For the whole patient group, the relapse rate after discontinuation did not exceed the pre-natalizumab relapse rate at any time, but 22 % of the patients showed rebound of relapses after discontinuation of natalizumab.
authors.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark, Per.Soelberg.Soerensen@regionh.dk.
authors.forename: Per Soelberg
authors.initials: PS
authors.lastname: Sorensen
authors.forename: Nils
authors.initials: N
authors.lastname: Koch-Henriksen
authors.forename: Thor
authors.initials: T
authors.lastname: Petersen
authors.forename: Mads
authors.initials: M
authors.lastname: Ravnborg
authors.forename: Annette
authors.initials: A
authors.lastname: Oturai
authors.forename: Finn
authors.initials: F
authors.lastname: Sellebjerg
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D003718:Denmark; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000139:chemically induced* / Q000188:drug therapy*; D000069442:Natalizumab; D012008:Recurrence; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D000069442:Natalizumab
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