Treatment of progressive multiple sclerosis from the neurologist’s perspective Review article
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Abstract
In the past two decades we have seen profound change in the treatment of multiple sclerosis (MS) but majority of therapies are dedicated for relapsing-remitting form. Prognosis in primary and secondary MS remains poor and usually patients tended to get worse over time. Immunosupressive therapy has been used in MS since 60’. Mitoxantrone is the only medication approved for the treatment of secondary progressive MS, although it also carries on indication for progressive relapsing MS. Some progressive MS patients may stabilize after treatment with cyclophosphamide. Azathioprine or methotrexate may be an alternative for progressive MS patients. Intense immunosuppression followed by autologous hematopoietic stem cell transplantation (AHSCT) has been used in the last 20 years for the treatment of aggressive forms of MS. The safety of AHSCT has improved in the last years, but the transplant-related mortality is still nowadays of about 1–2%, pointing out that a careful selection of patients to submit to AHSCT is mandatory. Results of trials with immunosupressives were often inconclusive or negative. In the last years monoclonal antibodies, rituximab and ocrelizumab, have been tested as treatments for progressive MS. Results of these trials were promising and give hope for effectiveness therapy in this form of MS.
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References
2. Lublin F.D.: New multiple sclerosis phenotypic classification. Eur. Neurol. 2014; 72(supl. 1): 1-5.
3. Walczak A.: Postępująca postać stwardnienia rozsianego – charakterystyka, przebieg i rokowanie. MS Report 2015; 4(15): 14-18.
4. Hartung H.P., Gonsette R., König N. et al.: Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 2002; 360: 2018-2025.
5. Stankiewicz J., Kolb H., Karni A. et al.: Role of immunosupressive therapy for the treatment of multiple sclerosis. Neurotherapeutics 2013; 10: 77-88.
6. Okuda D.T.: Immunosuppressive treatments in multiple sclerosis. Handb. Clin. Neurol. 2014; 122: 503-511.
7. 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: 153-159.
8. Grey Née Cotte S., Salmen Née Stroet A., von Ahsen N.: Lack of efficacy of mitoxantrone in primary progressive Multiple Sclerosis irrespective of pharmacogenetic factors: a multi-center, retrospective analysis. J. Neuroimmunol. 2015; 278: 277-279.
9. Fleischer V., Salmen A., Kollar S. et al.: Cardiotoxicity of Mitoxantrone Treatment in a German Cohort of 639 Multiple Sclerosis Patients. J. Clin. Neurol. 2014; 10(4): 289-295.
10. Le Page E., Leray E., Edan G.; French Mitoxantrone Safety Group: Long-term safety profile of mitoxantrone in a French cohort of 802 multiple sclerosis patients: a 5-year prospective study. Mult. Scler. 2011; 17(7): 867-875.
11. Ellis R., Brown S., Boggild M.: Therapy-related acute leukaemia with mitoxantrone: four years on, what is the risk and can it be limited? Mult. Scler. 2015; 21(5): 642-645.
12. Patti F., Lo Fermo S.: Lights and shadows of cyclophosphamide in the treatment of multiple sclerosis. Autoimmune Dis. 2011; 2011: 1-14.
13. Awad A., Stűve O.: Cyclophosphamide in multiple sclerosis: scientific rationale, history and novel treatment paradigms. Ther. Adv. Neurol. Disord. 2009; 2(6): 357-368.
14. Le Bouc R., Zephir H., Majed B. et al.: No increase in cancer incidence detected after cyclophosphamide in a French cohort of patients with progressive multiple sclerosis. MSJ 2012; 18(1): 55-63.
15. Faulkner M.: Risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis. Expert. Opin. Drug. Saf. 2015; 14(11): 1737-1748.
16. Currier R.D., Haerer A.F, Meydrech E.F.: Low dose oral methotrexate treatment of multiple sclerosis: a pilot study. J. Neurol. Neurosurg. Psychiatry 1993; 56(11): 1217-1218.
17. Goodkin D.E., Rudick R.A., VanderBrug Medendorp S. et al.: Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis. Ann. Neurol. 1995; 37(1): 30-40.
18. Sadiq S.A., Simon E.V., Puccio L.M.: Intrathecal methotrexate treatment in multiple sclerosis. J. Neurol. 2010; 257(11): 1806-1811.
19. Rommer P.S., Dörner T., Freivogel K.: Safety and Clinical Outcomes of Rituximab Treatment in Patients with Multiple Sclerosis and Neuromyelitis Optica: Experience from a National Online Registry (GRAID). J. Neuroimmune Pharmacol. 2016; 11(1): 1-8.
20. Hawker K., O’Connor P., Freedman M.S. et al.: Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann. Neurol. 2009; 66(4): 460-471.
21. Komori M., Lin Y.C., Cortese I.: Insufficient disease inhibition by intrathecal rituximab in progressive multiple sclerosis. Ann. Clin. Transl. Neurol. 2016; 3(3): 166-179.
22. Sorensen P.S., Blinkenberg M.: The potential role for ocrelizumab in the treatment of multiple sclerosis: current evidence and future prospects. Ther. Adv. Neurol. Disord. 2016; 9(10): 44-52.
23. Montalban X., Hemmer B., Rammohan K. et al.: Efficacy and safety of ocrelizumab in primary progressive multiple sclerosis – results of the placebo-controlled, double-blind, Phase III ORATORIO study. ECTRIMS Online Library 2015: 116701.
24. Mancardi G.L., Sormani M.P., Gualandi F.: Autologous hematopoietic stem cell transplantation in multiple sclerosis: a phase II trial. Neurology 2015; 84(10): 981-988.
25. Murano P.A., Pasquini M., Atkins H.: Long term outcomes after autologous hematopoietic stem cell transplantation for treatment of MS. ECTRIMS Online Library 2015; 116682.