title: Lack of efficacy of mitoxantrone in primary progressive Multiple Sclerosis irrespective of pharmacogenetic factors: a multi-center, retrospective analysis.
abstract: BACKGROUND
  Mitoxantrone is used on an off-label basis in primary progressive MS (PPMS). ABC-transporter-genotypes are associated with therapeutic response in relapsing/secondary progressive MS (RP/SPMS).
  
  
  OBJECTIVE
  To evaluate potential pharmacogenetic response markers for mitoxantrone in PPMS.
  
  
  METHODS
  41 mitoxantrone-treated PPMS-patients, 155 mitoxantrone-treated RP/SPMS-patients and 43 PPMS-controls were retrospectively assessed for clinical therapy-response and in correlation with four single-nucleotide-polymorphisms in ABCB1- and ABCG2-genes.
  
  
  RESULTS
  53.7% PPMS-patients were mitoxantrone-responders, in comparison to 78.1% of RP/SPMS-patients (p=0.039). There was no association between genotype and treatment response.
  
  
  CONCLUSIONS
  Our data discourages the use of mitoxantrone in PPMS regardless of pharmacogenetic response markers previously described in RP/SPMS.
authors.affiliation: Department of Neurology, St. Josef-Hospital, Ruhr University, Bochum, Germany.
authors.forename: Steffi
authors.initials: S
authors.lastname: Grey Née Cotte
authors.affiliation: Department of Neurology, St. Josef-Hospital, Ruhr University, Bochum, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Salmen Née Stroet
authors.affiliation: Department of Clinical Chemistry, Medical Faculty, University of Göttingen, Germany.
authors.forename: Nico
authors.initials: N
authors.lastname: von Ahsen
authors.affiliation: Marianne-Strauß-Klinik, Berg, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Starck
authors.affiliation: Department of Neurology, University of Rostock, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Winkelmann
authors.affiliation: Department of Neurology, University of Rostock, Germany.
authors.forename: Uwe K
authors.initials: UK
authors.lastname: Zettl
authors.affiliation: Department of Neurology-Neuroimmunology, Centre d'EsclerosiMúltiple de Catalunya (Cemcat), Institut de RecercaValld'Hebron (VHIR), Hospital UniversitariValld´Hebron, UniversitatAutònoma de Barcelona, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Comabella
authors.affiliation: Department of Neurology-Neuroimmunology, Centre d'EsclerosiMúltiple de Catalunya (Cemcat), Institut de RecercaValld'Hebron (VHIR), Hospital UniversitariValld´Hebron, UniversitatAutònoma de Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.affiliation: University Medicine Mainz, Johannes Gutenberg University Mainz, Department of Neurology, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Zipp
authors.affiliation: University Medicine Mainz, Johannes Gutenberg University Mainz, Department of Neurology, Germany.
authors.forename: Vinzenz
authors.initials: V
authors.lastname: Fleischer
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Kruse
authors.affiliation: Department of Neurology, St. Josef-Hospital, Ruhr University, Bochum, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.affiliation: Department of Neurology, St. Josef-Hospital, Ruhr University, Bochum, Germany. Electronic address: Andrew.Chan@rub.de.
authors.forename: Andrew
authors.initials: A
authors.lastname: Chan
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D000700:Analgesics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000627:therapeutic use*; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy* / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D010597:Pharmacogenetics; D012189:Retrospective Studies
chemical_list: C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000700:Analgesics; D009363:Neoplasm Proteins; D008942:Mitoxantrone
keywords: Escalation therapy; Immunosuppression; Multi-drug resistance transporter; Pharmacogenetics