title: From natalizumab to fingolimod in eight weeks - Immunological, clinical, and radiological data in quest of the optimal switch.
abstract: Natalizumab (NZB) discontinuation during a treatment change is associated with recurrence of disease activity in a significant proportion of multiple sclerosis (MS) patients. The immunological basis why disease reactivation occurs in selected patients is unresolved. In search of a prognostic biomarker for a safe and effective transition from NZB to fingolimod, we monitored five parameters related to pharmacokinetic and pharmacodynamic effects of the two drugs in 12 MS patients until six months on fingolimod. Clearance of free and cell-bound NZB, re-expression of alpha-4, and fingolimod-mediated changes on CD8+ and CD4+ T cell subsets showed pronounced interindividual variability. Higher frequencies of memory CD8+ T cells after six months on fingolimod were the sole association with disease reactivation. None of the investigated parameters thus had potential as prognostic biomarker for the outcome of the switch. Our findings rather support the thesis of broad interindividual differences in the immunopathogenesis of MS.
authors.affiliation: Department of Neurology, Paracelsus Medical University Salzburg, Salzburg, Austria. Electronic address: a.harrer@salk.at.
authors.forename: Andrea
authors.initials: A
authors.lastname: Harrer
authors.affiliation: Department of Neurology, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Pilz
authors.affiliation: Department of Neurology, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Katrin
authors.initials: K
authors.lastname: Oppermann
authors.affiliation: Department of Neurology, Paracelsus Medical University Salzburg, Salzburg, Austria; Department of Molecular Biology, Paris-Lodron University, Salzburg, Austria.
authors.forename: Marlene
authors.initials: M
authors.lastname: Sageder
authors.affiliation: Department of Laboratory Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Afazel
authors.affiliation: Department of Laboratory Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Haschke-Becher
authors.affiliation: Department of Immunopathology, Sanquin Research and Academic Centre, Amsterdam, The Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: Rispens
authors.affiliation: Laboratory for Monoclonal Therapeutics, Sanquin Diagnostics, Amsterdam, The Netherlands.
authors.forename: Annick
authors.initials: A
authors.lastname: de Vries
authors.affiliation: Division of Neuroradiology, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Mark
authors.initials: M
authors.lastname: McCoy
authors.affiliation: Division of Neuroradiology, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Vlado
authors.initials: V
authors.lastname: Stevanovic
authors.affiliation: Research Office, Biostatistics, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hitzl
authors.affiliation: Department of Neurology, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Eugen
authors.initials: E
authors.lastname: Trinka
authors.affiliation: Department of Laboratory Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria; Research Institute for Neurointervention, Paracelsus Medical University Salzburg, Salzburg, Austria; Department of Neurology, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kraus
authors.affiliation: Department of Neurology, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Johann
authors.initials: J
authors.lastname: Sellner
authors.affiliation: Department of Neurology, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Wipfler
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000532:radiotherapy; D000069442:Natalizumab / Q000627:therapeutic use*; D011859:Radiography / Q000379:methods; D012008:Recurrence; D055815:Young Adult
chemical_list: D000069442:Natalizumab; D000068876:Fingolimod Hydrochloride
keywords: Biomarkers; Fingolimod; Flow cytometry; Multiple sclerosis; Natalizumab; Treatment change