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.

CONCLUSION:

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

• Authors: 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
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 278 Pg. 277-9 (Jan 15 2015) ISSN: 1872-8421 [Electronic] Netherlands
• PMID: 25468777 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• 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

Topics

• 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, genetics)
• Neoplasm Proteins (genetics)
• Pharmacogenetics
• Retrospective Studies