title: Assessment of immune functions and MRI disease activity in relapsing-remitting multiple sclerosis patients switching from natalizumab to fingolimod (ToFingo-Successor).
abstract: BACKGROUND
  In light of the increased risk of progressive multifocal encephalopathy (PML) development under long-term treatment with the monoclonal antibody natalizumab which is approved for treatment of active relapsing remitting multiple sclerosis (RRMS), there is a clear need for alternative treatment options with comparable efficacy and reduced PML risk. One such option is fingolimod, a functional sphingosin-1-receptor antagonist that has been approved as first oral drug for treatment of active RRMS. However, the optimal switching design in terms of prevention of disease reoccurrence is still unknown. Moreover, potential additive effects of both drugs on immune functions, especially with regard to migration, have not yet been evaluated.
  
  
  METHODS
  This is an exploratory, open-label, monocentric, investigator-initiated clinical trial. Fifteen RRMS patients under stable treatment with natalizumab will receive one last natalizumab infusion followed by a wash-out period of 8 weeks before fingolimod treatment initiation for a period of 24 weeks. Disease activity under natalizumab and during switching will be closely monitored by assessment of relapse rate and disease severity as well as high-frequent high-resolution magnetic resonance imaging including quantitative diffusion tensor imaging. Immunological assays include longitudinal assessment of adhesion molecule expression, functional evaluation of the migratory capacity of immune cells in an in-vitro model of the blood-brain-barrier, and the quality of cellular antiviral immune responses.
  
  
  CONCLUSIONS
  Our trial represents the first detailed and longitudinal functional analysis of key immunological parameters in the process of switching from natalizumab and fingolimod, especially with regard to potential additive effects of both drugs on trafficking and immune surveillance. Moreover, our study will generate valuable information about even subtle disease exacerbations as consequence of natalizumab cessation, which will help to understand whether a switching protocol containing a wash-out period of 8 weeks before fingolimod treatment is appropriate in terms of disease stability.
authors.affiliation: Department of neurology, University Hospital Münster, Albert-Schweitzer-Campus 1, building A1, Münster, 48149, Germany. luisa.klotz@ukmuenster.de.
authors.forename: Luisa
authors.initials: L
authors.lastname: Klotz
authors.affiliation: Department of neurology, University Hospital Münster, Albert-Schweitzer-Campus 1, building A1, Münster, 48149, Germany. berit.gruetzke@gmail.com.
authors.forename: Berit
authors.initials: B
authors.lastname: Grützke
authors.affiliation: Institute of biostatistics and clinical research, Westfaelische Wilhelms-University Münster, Münster, Germany. maria.eveslage@ukmuenster.de.
authors.forename: Maria
authors.initials: M
authors.lastname: Eveslage
authors.affiliation: Department of neurology, University Hospital Münster, Albert-Schweitzer-Campus 1, building A1, Münster, 48149, Germany. deppe@uni-muenster.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Deppe
authors.affiliation: Department of neurology, University Hospital Münster, Albert-Schweitzer-Campus 1, building A1, Münster, 48149, Germany. catharina.gross@ukmuenster.de.
authors.forename: Catharina C
authors.initials: CC
authors.lastname: Gross
authors.affiliation: Department of neurology, University Hospital Münster, Albert-Schweitzer-Campus 1, building A1, Münster, 48149, Germany. lucienne.kirstein@ukmuenster.de.
authors.forename: Lucienne
authors.initials: L
authors.lastname: Kirstein
authors.affiliation: Department of neurology, University Hospital Münster, Albert-Schweitzer-Campus 1, building A1, Münster, 48149, Germany. anita.posevitz-fejfar@ukmuenster.de.
authors.forename: Anita
authors.initials: A
authors.lastname: Posevitz-Fejfar
authors.affiliation: Department of neurology, University Hospital Münster, Albert-Schweitzer-Campus 1, building A1, Münster, 48149, Germany. tilman.schneider-hohendorf@ukmuenster.de.
authors.forename: Tilman
authors.initials: T
authors.lastname: Schneider-Hohendorf
authors.affiliation: Department of neurology, University Hospital Münster, Albert-Schweitzer-Campus 1, building A1, Münster, 48149, Germany. nicholas.schwab@ukmuenster.de.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Schwab
authors.affiliation: Department of neurology, University Hospital Münster, Albert-Schweitzer-Campus 1, building A1, Münster, 48149, Germany. sven.meuth@ukmuenster.de.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.affiliation: Department of neurology, University Hospital Münster, Albert-Schweitzer-Campus 1, building A1, Münster, 48149, Germany. heinz.wiendl@ukmuenster.de.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
mesh_terms: D018450:Disease Progression; D000068876:Fingolimod Hydrochloride / Q000627:therapeutic use*; D006801:Humans; D008279:Magnetic Resonance Imaging; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D000069442:Natalizumab / Q000627:therapeutic use*; D011446:Prospective Studies; D012306:Risk
chemical_list: D000069442:Natalizumab; D000068876:Fingolimod Hydrochloride