open access

Vol 54, No 1 (2020)
Research paper
Published online: 2020-01-10
Submitted: 2019-07-15
Accepted: 2019-11-11
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Is there a new place for mitoxantrone in the treatment of multiple sclerosis?

Sławomir Wawrzyniak, Łukasz Rzepiński
DOI: 10.5603/PJNNS.a2019.0069
·
Pubmed: 31922582
·
Neurol Neurochir Pol 2020;54(1):54-61.

open access

Vol 54, No 1 (2020)
Research paper
Published online: 2020-01-10
Submitted: 2019-07-15
Accepted: 2019-11-11

Abstract

Aim of the study. To compare the clinical and neuroradiological efficacy of mitoxantrone (MTX) in various forms of multiple sclerosis (MS), to ascertain whether there is a new place for the drug in the treatment regimen of the disease, as well as to determine its safety profile.

Clinical rationale for the study. Due to the increasing availability of new immunomodulatory therapies in multiple sclerosis (MS), there is a strong need to re-identify clinical variants and stages of the disease in which mitoxantrone (MTX) can be the most effective form of treatment.

Materials and methods. This was a retrospective, non-randomised, observational study evaluating a cohort of 100 MS patients (36 relapsing-remitting – RRMS, 36 secondary progressive – SPMS, and 28 primary progressive – PPMS). 59% of the RRMS patients had discontinued immunomodulatory therapies (IMTs) within the two years preceding MTX infusion. Patients’ disability levels, based on the Kurtzke Expanded Disability Status Scale (EDSS) as well as haematological and echocardiographic parameters, were assessed at baseline and before every infusion. Magnetic resonance imaging (MRI) were performed at entry and
after termination of treatment.

Results. We observed a decrease in the median EDSS score from 4.0 at baseline to 3.5 at the end of MTX infusion in the RRMS subgroup, an increase from 4.5 to 5.25 in the PPMS subgroup, and a stable value of 5 points in the SPMS subgroup (p < 0.0001). During the treatment period, 97% of patients with initial RRMS were free of exacerbations. The baseline EDSS in the RRMS subgroup, as well as the ineffectiveness of previous IMTs, suggested the beginning of conversion to SPMS. We found an 86% decrease in the proportion of patients with gadolinium-enhancing lesions on MRI after MTX infusions. There were no lifethreatening adverse events of MTX during the period of evaluation.

Conclusions and clinical implications. Mitoxantrone can be considered as a valuable therapeutic option for patients who are on the borderline of RRMS and SPMS.

Abstract

Aim of the study. To compare the clinical and neuroradiological efficacy of mitoxantrone (MTX) in various forms of multiple sclerosis (MS), to ascertain whether there is a new place for the drug in the treatment regimen of the disease, as well as to determine its safety profile.

Clinical rationale for the study. Due to the increasing availability of new immunomodulatory therapies in multiple sclerosis (MS), there is a strong need to re-identify clinical variants and stages of the disease in which mitoxantrone (MTX) can be the most effective form of treatment.

Materials and methods. This was a retrospective, non-randomised, observational study evaluating a cohort of 100 MS patients (36 relapsing-remitting – RRMS, 36 secondary progressive – SPMS, and 28 primary progressive – PPMS). 59% of the RRMS patients had discontinued immunomodulatory therapies (IMTs) within the two years preceding MTX infusion. Patients’ disability levels, based on the Kurtzke Expanded Disability Status Scale (EDSS) as well as haematological and echocardiographic parameters, were assessed at baseline and before every infusion. Magnetic resonance imaging (MRI) were performed at entry and
after termination of treatment.

Results. We observed a decrease in the median EDSS score from 4.0 at baseline to 3.5 at the end of MTX infusion in the RRMS subgroup, an increase from 4.5 to 5.25 in the PPMS subgroup, and a stable value of 5 points in the SPMS subgroup (p < 0.0001). During the treatment period, 97% of patients with initial RRMS were free of exacerbations. The baseline EDSS in the RRMS subgroup, as well as the ineffectiveness of previous IMTs, suggested the beginning of conversion to SPMS. We found an 86% decrease in the proportion of patients with gadolinium-enhancing lesions on MRI after MTX infusions. There were no lifethreatening adverse events of MTX during the period of evaluation.

Conclusions and clinical implications. Mitoxantrone can be considered as a valuable therapeutic option for patients who are on the borderline of RRMS and SPMS.

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Keywords

mitoxantrone, efficacy, relapsing-remitting multiple sclerosis, secondary progressive multiple sclerosis, disability

About this article
Title

Is there a new place for mitoxantrone in the treatment of multiple sclerosis?

Journal

Neurologia i Neurochirurgia Polska

Issue

Vol 54, No 1 (2020)

Pages

54-61

Published online

2020-01-10

DOI

10.5603/PJNNS.a2019.0069

Pubmed

31922582

Bibliographic record

Neurol Neurochir Pol 2020;54(1):54-61.

Keywords

mitoxantrone
efficacy
relapsing-remitting multiple sclerosis
secondary progressive multiple sclerosis
disability

Authors

Sławomir Wawrzyniak
Łukasz Rzepiński

References (37)
  1. Weinshenker BG, Bass B, Rice GP, et al. The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability. Brain. 1989; 112 ( Pt 1): 133–146.
  2. Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996; 46(4): 907–911.
  3. Confavreux C, Vukusic S. Natural history of multiple sclerosis: a unifying concept. Brain. 2006; 129(Pt 3): 606–616.
  4. Montalban X, Gold R, Thompson AJ, et al. ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis. Eur J Neurol. 2018; 25(2): 215–237.
  5. Cottrell DA, Kremenchutzky M, Rice GP, et al. The natural history of multiple sclerosis: a geographically based study. 5. The clinical features and natural history of primary progressive multiple sclerosis. Brain. 1999; 122 ( Pt 4): 625–639.
  6. Miller D, Leary S. Primary-progressive multiple sclerosis. The Lancet Neurology. 2007; 6(10): 903–912.
  7. EMD Serono, Inc. Novantrone (mitoxantrone) for injection concentrate [product monograph]. http://www.novantrone.com/assets/pdf/novantrone_prescribing_info. pdf. (October 20, 2007.).
  8. Fidler JM, DeJoy SQ, Smith FR, et al. Selective immunomodulation by the antineoplastic agent mitoxantrone. II. Nonspecific adherent suppressor cells derived from mitoxantrone-treated mice. J Immunol. 1986; 136(8): 2747–2754.
  9. Neuhaus O, Kieseier BC, Hartung HP. Mechanisms of mitoxantrone in multiple sclerosis--what is known? J Neurol Sci. 2004; 223(1): 25–27.
  10. Hartung HP, Gonsette R, König N, et al. Mitoxantrone in Multiple Sclerosis Study Group (MIMS). Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet. 2002; 360(9350): 2018–2025.
  11. Bhatia R, Singh N. Can We Treat Secondary Progressive Multiple Sclerosis Now? Ann Indian Acad Neurol. 2019; 22(2): 131–136.
  12. https://www.ema.europa.eu/en/documents/referral/novantrone-article-30-referral-annex-iii_en.pdf.
  13. Buttmann M. Where mitoxantrone for multiple sclerosis is still valuable in 2018. Eur J Neurol. 2018; 25(12): 1400–1401.
  14. Giovannoni G. Disease-modifying treatments for early and advanced multiple sclerosis: a new treatment paradigm. Curr Opin Neurol. 2018; 31(3): 233–243.
  15. Mather FJ, Simon RM, Clark GM, et al. Cardiotoxicity in patients treated with mitoxantrone: Southwest Oncology Group phase II studies. Cancer Treat Rep. 1987; 71(6): 609–613.
  16. Goodin DS, Arnason BG, Coyle PK, et al. Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. The use of mitoxantrone (Novantrone) for the treatment of multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2003; 61(10): 1332–1338.
  17. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983; 33(11): 1444–1452.
  18. Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983; 13(3): 227–231.
  19. McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001; 50(1): 121–127.
  20. Polman CH, Reingold SC, Edan G, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005; 58(6): 840–846.
  21. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011; 69(2): 292–302.
  22. Scalfari A, Neuhaus A, Degenhardt A, et al. The natural history of multiple sclerosis: a geographically based study 10: relapses and long-term disability. Brain. 2010; 133(Pt 7): 1914–1929.
  23. Chartier N, Epstein J, Soudant M, et al. Clinical follow-up of 411 patients with relapsing and progressive multiple sclerosis 10 years after discontinuing mitoxantrone treatment: a real-life cohort study. Eur J Neurol. 2018; 25(12): 1439–1445.
  24. Edan G, Miller D, Clanet M, et al. Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria. J Neurol Neurosurg Psychiatry. 1997; 62(2): 112–118.
  25. Debouverie M, Taillandier L, Pittion-Vouyovitch S, et al. Clinical follow-up of 304 patients with multiple sclerosis three years after mitoxantrone treatment. Mult Scler. 2007; 13(5): 626–631.
  26. Buttinelli C, Clemenzi A, Borriello G, et al. Mitoxantrone treatment in multiple sclerosis: a 5-year clinical and MRI follow-up. Eur J Neurol. 2007; 14(11): 1281–1287.
  27. Esposito F, Radaelli M, Martinelli V, et al. Comparative study of mitoxantrone efficacy profile in patients with relapsing-remitting and secondary progressive multiple sclerosis. Mult Scler. 2010; 16(12): 1490–1499.
  28. Le Page E, Leray E, Taurin G, et al. Mitoxantrone as induction treatment in aggressive relapsing remitting multiple sclerosis: treatment response factors in a 5 year follow-up observational study of 100 consecutive patients. J Neurol Neurosurg Psychiatry. 2008; 79(1): 52–56.
  29. Cocco E, Marchi P, Sardu C, et al. Mitoxantrone treatment in patients with early relapsing-remitting multiple sclerosis. Mult Scler. 2007; 13(8): 975–980.
  30. Edan G, Comi G, Le Page E, et al. French–Italian Mitoxantrone Interferon-beta-1b Trial Group. Mitoxantrone prior to interferon beta-1b in aggressive relapsing multiple sclerosis: a 3-year randomised trial. J Neurol Neurosurg Psychiatry. 2011; 82(12): 1344–1350.
  31. Katz Sand I, Krieger S, Farrell C, et al. Diagnostic uncertainty during the transition to secondary progressive multiple sclerosis. Mult Scler. 2014; 20(12): 1654–1657.
  32. Lorscheider J, Buzzard K, Jokubaitis V, et al. MSBase Study Group. Defining secondary progressive multiple sclerosis. Brain. 2016; 139(Pt 9): 2395–2405.
  33. Filippini G, Del Giovane C, Vacchi L, et al. Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis. Cochrane Database Syst Rev. 2013(6): CD008933.
  34. Millefiorini E, Gasperini C, Pozzilli C, et al. Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome. J Neurol. 1997; 244(3): 153–159.
  35. van de Wyngaert FA, Beguin C, D'Hooghe MB, et al. A double-blind clinical trial of mitoxantrone versus methylprednisolone in relapsing, secondary progressive multiple sclerosis. Acta Neurol Belg. 2001; 101(4): 210–216.
  36. Martinelli Boneschi F, Rovaris M, Capra R, et al. Mitoxantrone for multiple sclerosis. Cochrane Database Syst Rev. 2005(4): CD002127.
  37. http://www.mz.gov.pl/leki/refundacja/programy-lekowe.

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