Saturday, 6 December 2014

Mitoxantrone limited use in PPMS

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. Lack of efficacy of mitoxantrone in primary progressive Multiple Sclerosis irrespective of pharmacogenetic factors: A multi-center, retrospective analysis.J Neuroimmunol. 2014 Nov 20. pii: S0165-5728(14)00978-3.

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.
Mitoxantrone is an anti-cancer drug that is sometimes used in aggressive MS. However its use is limited because it causes significant cardiac toxicology of the heart. It is also associated with a significant increase in cancers. ABCB1 is known as p glycoprotein, which we and others have shown disappear from lesion in acute and chronic MS, but it has been shown that ABCG1 = Breast cancer resistance protein  one is a drug pump on the blood vessel that kicks mitoxantrone out of the brain. A certain genetic variant had been associated with more entry of drug into the brain. This study suggests irrespective of this there is limited value in treating PPMSers. One suspects that if you remove the relapsing progressive people from the mix then the effect in progressive MS will minimal, based on the findings with other immunosuppressive agents

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