Lack of efficacy of mitoxantrone in primary progressive Multiple Sclerosis irrespective of pharmacogenetic factors: a multi-center, retrospective analysis

Steffi Grey Née Cotte; Anke Salmen Née Stroet; Nico von Ahsen; Michaela Starck; Alexander Winkelmann; Uwe K Zettl; Manuel Comabella; Xavier Montalban; Frauke Zipp; Vinzenz Fleischer; Niels Kruse; Ralf Gold; Andrew Chan

doi:10.1016/j.jneuroim.2014.11.017

Lack of efficacy of mitoxantrone in primary progressive Multiple Sclerosis irrespective of pharmacogenetic factors: a multi-center, retrospective analysis

J Neuroimmunol. 2015 Jan 15:278:277-9. doi: 10.1016/j.jneuroim.2014.11.017. Epub 2014 Nov 20.

Authors

Affiliations

¹ Department of Neurology, St. Josef-Hospital, Ruhr University, Bochum, Germany.
² Department of Clinical Chemistry, Medical Faculty, University of Göttingen, Germany.
³ Marianne-Strauß-Klinik, Berg, Germany.
⁴ Department of Neurology, University of Rostock, Germany.
⁵ Department of Neurology-Neuroimmunology, Centre d'EsclerosiMúltiple de Catalunya (Cemcat), Institut de RecercaValld'Hebron (VHIR), Hospital UniversitariValld´Hebron, UniversitatAutònoma de Barcelona, Spain.
⁶ University Medicine Mainz, Johannes Gutenberg University Mainz, Department of Neurology, Germany.
⁷ Institute of Neuropathology, University Medical Center Göttingen, Germany.
⁸ Department of Neurology, St. Josef-Hospital, Ruhr University, Bochum, Germany. Electronic address: Andrew.Chan@rub.de.

PMID: 25468777
DOI: 10.1016/j.jneuroim.2014.11.017

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.

Conclusion: Our data discourages the use of mitoxantrone in PPMS regardless of pharmacogenetic response markers previously described in RP/SPMS.

Keywords: Escalation therapy; Immunosuppression; Multi-drug resistance transporter; Pharmacogenetics.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B / genetics
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters / genetics
Adult
Analgesics / therapeutic use*
Female
Humans
Male
Middle Aged
Mitoxantrone / therapeutic use*
Multiple Sclerosis, Chronic Progressive / drug therapy*
Multiple Sclerosis, Chronic Progressive / genetics*
Neoplasm Proteins / genetics
Pharmacogenetics*
Retrospective Studies

Substances

ABCB1 protein, human
ABCG2 protein, human
ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters
Analgesics
Neoplasm Proteins
Mitoxantrone