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

Steffi Grey (nee Cotte); Anke Salmen (nee 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

Steffi Grey (nee Cotte), Anke Salmen (nee 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

Department of Medicine

Research output: Contribution to journal › Article › Research › peer-review

15 Citations (Scopus)

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. (C) 2014 Elsevier B.V. All rights reserved.

Original language	English
Pages (from-to)	277-279
Number of pages	3
Journal	Journal of Neuroimmunology
Volume	278
DOIs	https://doi.org/10.1016/j.jneuroim.2014.11.017
Publication status	Published - 15 Jan 2015

Keywords

Escalation therapy
Immunosuppression
Multi-drug resistance transporter
Pharmacogenetics

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Grey (nee Cotte), S., Salmen (nee Stroet), A., von Ahsen, N., Starck, M., Winkelmann, A., Zettl, U. K., Comabella, M., Montalban, X., Zipp, F., Fleischer, V., Kruse, N., Gold, R., & Chan, A. (2015). Lack of efficacy of mitoxantrone in primary progressive Multiple Sclerosis irrespective of pharmacogenetic factors: A multi-center, retrospective analysis. Journal of Neuroimmunology, 278, 277-279. https://doi.org/10.1016/j.jneuroim.2014.11.017

@article{73009a32d8f4404b922a00e914864a0d,

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.Conclusion: Our data discourages the use of mitoxantrone in PPMS regardless of pharmacogenetic response markers previously described in RP/SPMS. (C) 2014 Elsevier B.V. All rights reserved.",

keywords = "Escalation therapy, Immunosuppression, Multi-drug resistance transporter, Pharmacogenetics",

author = "\{Grey (nee Cotte)\}, Steffi and \{Salmen (nee Stroet)\}, Anke and \{von Ahsen\}, Nico and Michaela Starck and Alexander Winkelmann and Zettl, \{Uwe K.\} and Manuel Comabella and Xavier Montalban and Frauke Zipp and Vinzenz Fleischer and Niels Kruse and Ralf Gold and Andrew Chan",

year = "2015",

month = jan,

day = "15",

doi = "10.1016/j.jneuroim.2014.11.017",

language = "English",

volume = "278",

pages = "277--279",

journal = "Journal of Neuroimmunology",

issn = "0165-5728",

publisher = "Elsevier",

}

Grey (nee Cotte), S, Salmen (nee Stroet), A, von Ahsen, N, Starck, M, Winkelmann, A, Zettl, UK, Comabella, M, Montalban, X, Zipp, F, Fleischer, V, Kruse, N, Gold, R & Chan, A 2015, 'Lack of efficacy of mitoxantrone in primary progressive Multiple Sclerosis irrespective of pharmacogenetic factors: A multi-center, retrospective analysis', Journal of Neuroimmunology, vol. 278, pp. 277-279. https://doi.org/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. / Grey (nee Cotte), Steffi; Salmen (nee Stroet), Anke; von Ahsen, Nico et al.
In: Journal of Neuroimmunology, Vol. 278, 15.01.2015, p. 277-279.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Lack of efficacy of mitoxantrone in primary progressive Multiple Sclerosis irrespective of pharmacogenetic factors:

T2 - A multi-center, retrospective analysis

AU - Grey (nee Cotte), Steffi

AU - Salmen (nee Stroet), Anke

AU - von Ahsen, Nico

AU - Starck, Michaela

AU - Winkelmann, Alexander

AU - Zettl, Uwe K.

AU - Comabella, Manuel

AU - Montalban, Xavier

AU - Zipp, Frauke

AU - Fleischer, Vinzenz

AU - Kruse, Niels

AU - Gold, Ralf

AU - Chan, Andrew

PY - 2015/1/15

Y1 - 2015/1/15

N2 - 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. (C) 2014 Elsevier B.V. All rights reserved.

AB - 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. (C) 2014 Elsevier B.V. All rights reserved.

KW - Escalation therapy

KW - Immunosuppression

KW - Multi-drug resistance transporter

KW - Pharmacogenetics

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UR - https://www.scopus.com/pages/publications/84920896770

U2 - 10.1016/j.jneuroim.2014.11.017

DO - 10.1016/j.jneuroim.2014.11.017

M3 - Article

C2 - 25468777

SN - 0165-5728

VL - 278

SP - 277

EP - 279

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

ER -

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

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Keywords

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