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

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

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

16 Scopus citations

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.

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
State	Published - 15 Jan 2015
Externally published	Yes

Keywords

Escalation therapy
Immunosuppression
Multi-drug resistance transporter
Pharmacogenetics

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10.1016/j.jneuroim.2014.11.017

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Grey Née Cotte, S., Salmen Née 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{e0ed37efeb9b46e7aad23e0e27eca159,

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.",

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

author = "\{Grey N{\'e}e Cotte\}, Steffi and \{Salmen N{\'e}e 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",

note = "Publisher Copyright: {\textcopyright} 2014 Elsevier B.V.",

year = "2015",

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day = "15",

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

language = "English",

volume = "278",

pages = "277--279",

journal = "Journal of Neuroimmunology",

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publisher = "Elsevier B.V.",

}

Grey Née Cotte, S, Salmen Née 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

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 Née Cotte, Steffi

AU - Salmen Née 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.

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.

KW - Escalation therapy

KW - Immunosuppression

KW - Multi-drug resistance transporter

KW - Pharmacogenetics

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

AN - SCOPUS:84920896770

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

Abstract

Keywords

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