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

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.