Journal of Isfahan Medical School

Journal of Isfahan Medical School

Comparing the Efficacy of Monthly Cyclophosphamide as Monotherapy versus Daily Fingolimod in Relapsing Remitting and Secondary Progressive Multiple Sclerosis

Document Type : Original Article (s)

Authors
Vahid Shaygannezhad 1
Hassan Amini 2
1 Associate Professor, Isfahan Neuroscienseces Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2 Resident, Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Abstract
Background: The aim of this study was to determine the efficacy of monthly cyclophosphamide and daily fingolimod in treatment of patients with multiple sclerosis (MS) and to compare these two treatment strategies.Methods: In a clinical trial study, 30 patients with relapsing remitting multiple sclerosis (RRMS) were enrolled. 15 patients were treated by cyclophosphamide and 15 by fingolimod for six months. The expanded disability status scale (EDSS) score and relapse rate were measured and compared between the two groups.Findings: The mean differences of EDSS in the two groups were -0.03 ± 0.17 and 0.33 ± 0.18, respectively and the decrease of EDSS in fingolimod group was significantly higher than the cyclophosphamide group (P < 0.001). In the cyclophosphamide group, there were 4 patients without recurrence, 10 single and 1 double flares; while in fingolimod group, only 4 patients had a single relapse. The differences in after-treatment relapses among the two groups was statistically significant (P = 0.023).Conclusion: Using daily fingolimod is better than the cyclophosphamide for prevention of relapse and improvement of EDSS in patients with relapsing remitting multiple sclerosis; but treatment of multiple sclerosis with this drug depend on patient's clinical status, intensity of the disease, and idea of neurologist. However, more studies are recommended for determining the side effects in long term use of fingolimod.
Keywords
Multiple Sclerosis
Cyclophosphamide
Fingolimod
Relapsing remitting
  1. Patti F, Lo Fermo S. Lights and Shadows of cyclophosphamide in the treatment of multiple sclerosis. Autoimmune Dis 2011; 2011: 961702.
  2. Weinshenker BG. The natural history of multiple sclerosis. Neurol Clin 1995; 13(1): 119-46.
  3. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33(11): 1444-52.
  4. Banwell B, Ghezzi A, Bar-Or A, Mikaeloff Y, Tardieu M. Multiple sclerosis in children: clinical diagnosis, therapeutic strategies, and future directions. Lancet Neurol 2007; 6(10): 887-902.
  5. Lassmann H, Bruck W, Lucchinetti C. Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy. Trends Mol Med 2001; 7(3): 115-21.
  6. Krishnan C, Kaplin AI, Brodsky RA, Drachman DB, Jones RJ, Pham DL, et al. Reduction of disease activity and disability with high-dose cyclophosphamide in patients with aggressive multiple sclerosis. Arch Neurol 2008; 65(8): 1044-51.
  7. Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354(9): 899-910.
  8. Kappos L, Radue EW, O'Connor P, Polman C, Hohlfeld R, Calabresi P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010; 362(5): 387-401.
  9. Brodsky RA, Jones RJ. Aplastic anaemia. Lancet 2005; 365(9471): 1647-56.
  10. Weiner HL, Cohen JA. Treatment of multiple sclerosis with cyclophosphamide: critical review of clinical and immunologic effects. Mult Scler 2002; 8(2): 142-54.
  11. Hommes OR, Prick JJ, Lamers KJ. Treatment of the chronic progressive form of multiple sclerosis with a combination of cyclophosphamide and prednisone. Clin Neurol Neurosurg 1975; 78(1): 59-72.
  12. Fassas A, Anagnostopoulos A, Kazis A, Kapinas K, Sakellari I, Kimiskidis V, et al. Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study. Bone Marrow Transplant 1997; 20(8): 631-8.
  13. Blanco Y, Saiz A, Carreras E, Graus F. Autologous haematopoietic-stem-cell transplantation for multiple sclerosis. Lancet Neurol 2005; 4(1): 54-63.
  14. Saccardi R, Kozak T, Bocelli-Tyndall C, Fassas A, Kazis A, Havrdova E, et al. Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database. Mult Scler 2006; 12(6): 814-23.
  15. Harrison DM, Gladstone DE, Hammond E, Cheng J, Jones RJ, Brodsky RA, et al. Treatment of relapsing-remitting multiple sclerosis with high-dose cyclophosphamide induction followed by glatiramer acetate maintenance. Mult Scler 2012; 18(2): 202-9.
  16. Gladstone DE, Peyster R, Baron E, Friedman-Urevich S, Sibony P, Melville P, et al. High-dose cyclophosphamide for moderate to severe refractory multiple sclerosis: 2-year follow-up (investigational new drug No. 65863). Am J Ther 2011; 18(1): 23-30.
  17. Schwartzman RJ, Simpkins N, Alexander GM, Reichenberger E, Ward K, Lindenberg N, et al. High-dose cyclophosphamide in the treatment of multiple sclerosis. CNS Neurosci Ther 2009; 15(2): 118-27.
  18. DeZern AE, Petri M, Drachman DB, Kerr D, Hammond ER, Kowalski J, et al. High-dose cyclophosphamide without stem cell rescue in 207 patients with aplastic anemia and other autoimmune diseases. Medicine (Baltimore) 2011; 90(2): 89-98.
  19. Smith DR, Weinstock-Guttman B, Cohen JA, Wei X, Gutmann C, Bakshi R, et al. A randomized blinded trial of combination therapy with cyclophosphamide in patients-with active multiple sclerosis on interferon beta. Mult Scler 2005; 11(5): 573-82.
  20. Reggio E, Nicoletti A, Fiorilla T, Politi G, Reggio A, Patti F. The combination of cyclophosphamide plus interferon beta as rescue therapy could be used to treat relapsing-remitting multiple sclerosis patients-- twenty-four months follow-up. J Neurol 2005; 252(10): 1255-61.
  21. Zipoli V, Portaccio E, Hakiki B, Siracusa G, Sorbi S, Amato MP. Intravenous mitoxantrone and cyclophosphamide as second-line therapy in multiple sclerosis: an open-label comparative study of efficacy and safety. J Neurol Sci 2008; 266(1-2): 25-30.
  22. Hauser SL, Dawson DM, Lehrich JR, Beal MF, Kevy SV, Propper RD, et al. Intensive immunosuppression in progressive multiple sclerosis. A randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH. N Engl J Med 1983; 308(4): 173-80.
  23. Hohol MJ, Olek MJ, Orav EJ, Stazzone L, Hafler DA, Khoury SJ, et al. Treatment of progressive multiple sclerosis with pulse cyclophosphamide/methylprednisolone: response to therapy is linked to the duration of progressive disease. Mult Scler 1999; 5(6): 403-9.
  24. Weiner HL, Mackin GA, Orav EJ, Hafler DA, Dawson DM, LaPierre Y, et al. Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the Northeast Cooperative Multiple Sclerosis Treatment Group. Neurology 1993; 43(5): 910-8.
  25. Miller DM, Kinkel RP. Health-related quality of life assessment in multiple sclerosis. Rev Neurol Dis 2008; 5(2): 56-64.
  26. Rammohan KW, Shoemaker J. Emerging multiple sclerosis oral therapies. Neurology 2010; 74(Suppl 1): S47-S53.
  27. Cohen JA, Barkhof F, Comi G, Hartung HP, Khatri BO, Montalban X, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010; 362(5): 402-15.
  28. Lugaresi A, di IM, Travaglini D, Pietrolongo E, Pucci E, Onofrj M. Risk-benefit considerations in the treatment of relapsing-remitting multiple sclerosis. Neuropsychiatr Dis Treat 2013; 9: 893-914.
  29. Kappos L, Radue EW, O'Connor P, Polman C, Hohlfeld R, Calabresi P, et al. Phase 3 FREEDOMS study extension: Fingolimod (FTY720) efficacy in patients with relapsing-remitting multiple sclerosis receiving continuous or placebo-fingolimod switched therapy for up to 4 years. Proceedings of the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis; 2012 Oct 10-13: Lyon, France.
Journal of Isfahan Medical School
Volume 35, Issue 435 - Serial Number 435
May and June 2017
Pages 719-725

  • Receive Date 07 March 2017
  • Accept Date 06 April 2022