title: Severe disease reactivation in four patients with relapsing-remitting multiple sclerosis after fingolimod cessation.
abstract: OBJECTIVE
  Fingolimod is a well-established, highly effective immunomodulatory treatment for patients with relapsing-remitting multiple sclerosis (RRMS). However, little is known about disease course after its discontinuation.
  
  
  METHODS
  This is a case series on four patients with RRMS who had a severe reactivation after fingolimod discontinuation.
  
  
  RESULTS
  One patient had pretreatment with glatiramer acetate, interferon-β 1b and interferon-β 1a and another with interferon-β 1a, intravenous immunoglobulins and natalizumab whereas the other two were therapy naïve before fingolimod initiation. Patients were treated with fingolimod for two, thirty, forty-five and seventy-eight months, respectively. Fingolimod had to be discontinued because of persisting lymphopenia, severe varicella zoster virus infection, subarachnoid hemorrhage, and increased liver function enzymes, respectively. Between two to four months after fingolimod cessation these patients had a severe relapse. Cerebral magnetic resonance imaging (MRI) at this point revealed multiple new lesions, partially with contrast ring enhancement. Partial recovery was achieved after steroid pulse therapy followed by plasma exchange in two patients.
  
  
  CONCLUSIONS
  Despite the limited evidence from our case series on potential disease reactivation exceeding pre-fingolimod activity in a subgroup of RRMS patients, particularly patients with previously high disease activity should undergo frequent clinical as well as radiological monitoring after fingolimod discontinuation.
authors.affiliation: University Hospital Freiburg, Department of Neurology and Neurophysiology, Breisacher Strasse 64, D-79106 Freiburg, Germany. Electronic address: benjamin.berger@uniklinik-freiburg.de.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Berger
authors.affiliation: University Hospital Freiburg, Department of Neurology and Neurophysiology, Breisacher Strasse 64, D-79106 Freiburg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Baumgartner
authors.affiliation: University Hospital Freiburg, Department of Neurology and Neurophysiology, Breisacher Strasse 64, D-79106 Freiburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Rauer
authors.affiliation: University Hospital Freiburg, Department of Neuroradiology, Breisacher Strasse 64, D-79106 Freiburg, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Mader
authors.affiliation: University Hospital Freiburg, Department of Neuroradiology, Breisacher Strasse 64, D-79106 Freiburg, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Luetzen
authors.affiliation: Medical practice, Leutkirchstrasse 37, D-77723 Gengenbach, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Farenkopf
authors.affiliation: University Hospital Freiburg, Department of Neurology and Neurophysiology, Breisacher Strasse 64, D-79106 Freiburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Stich
mesh_terms: D000328:Adult; D004185:Disability Evaluation; D005260:Female; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D011409:Propylene Glycols / Q000627:therapeutic use*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine
keywords: Cessation; Fingolimod; Multiple sclerosis; Reactivation; Rebound