Safety and efficacy of fingolimod in multiple sclerosis after the failure of first-line therapy Original article

Article Sidebar

Requires Subscription PDF (Język Polski)


Published: Mar 31, 2016
Keywords:
multiple sclerosis, second-line therapy, fingolimod

Main Article Content

Przemysław Puz
Oddział Neurologii, Samodzielny Publiczny Szpital Kliniczny nr 7, Śląski Uniwersytet Medyczny w Katowicach, Górnośląskie Centrum Medyczne im. prof. Leszka Gieca
Anetta Lasek-Bal
Oddział Neurologii, Samodzielny Publiczny Szpital Kliniczny nr 7, Śląski Uniwersytet Medyczny w Katowicach, Górnośląskie Centrum Medyczne im. prof. Leszka Gieca

Abstract

Aim: In Poland, the availability of therapies in relapsing-remitting multiple sclerosis (RRMS) is regulated by the National Health Fund (NFZ, Narodowy Fundusz Zdrowia) regulations, according to which the second-line therapy is now possible only with two medications (natalizumab, fingolimod) and only in patients, who suffered relapses and developed new lesions observed in MRI during first-line treatment in the period of minimum 12 months. The aim of this study is to evaluate the effects of second-line treatment with fingolimod by means of the analysis of the impact of the therapy on the frequency of relapses, the degree of disability progression and the occurrence of side effects.


Methods: Analysis covered 30 RRMS patients switched from first-line therapy to fingolimod. The annualized relapse rate, disability progression (assessed with Expanded Disability Status Scale, EDSS) and MRI results (new or enlarged T2 lesions and new Gd-positive lesions) before and after switching were compared. The occurrence of adverse events was also assessed.


Results: The annualized relapse rate for fingolimod therapy was significantly lower than for first-line therapy (0.26 ± 0.65 vs. 2.08 ± 0.87; p = 0.00005). The mean number of new or enlarged T2 and Gd+ lesions in MRI after one-year fingolimod treatment was significantly lower in comparison to MRI performed at the end of the first-line therapy (for T2: 0.6 vs 4.23; p = 0.0004, for Gd+: 0.2 vs. 1.83; p = 0.0009). Median of EDSS progression with first-line therapy was significantly higher than that with fingolimod treatment (p = 0.00002).


Conclusions: Treatment with fingolimod as a second-line therapy in RRMS patients is safe and effective. Less restrictive criteria for switching should be considered.

Article Details

Issue
Vol 5 No 1(16) (2016)
Section
Articles

Copyright © by Medical Education. All rights reserved.

References

1. Giovannoni G., Turner B., Gnanapavan S. et al.: Is it time to target no evident disease activity (NEDA) in multiple sclerosis? Mult. Scler. Relat. Disord. 2015; 4(4): 329-333.
2. Banwell B., Giovannoni G., Hawkes C., Lublin F.D.: Editors’ welcome and a working definition for a multiple sclerosis cure. Mult. Scler. Relat. Disord. 2013; 2: 65-67.
3. Krieger S.: Multiple sclerosis therapeutic pipeline: opportunities and challenges. Mt. Sinai J. Med. 2011; 78(2): 192-206.
4. Khan O., Rieckmann P., Boyko A. et al.; GALA Study Group: Three times weekly glatiramer acetate in relapsing-remitting multiple sclerosis. Ann. Neurol. 2013; 73(6): 705-713.
5. Calabresi P.A., Kieseier B.C., Arnold D.L. et al.; ADVANCE Study Investigators: Pegylated interferon β-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study. Lancet Neurol. 2014; 13(7): 657-665.
6. Kappos L., Radue E.W., O’Connor P. et al.; FREEDOMS Study Group: A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N. Engl. J. Med. 2010; 362(5): 387-401.
7. Polman C.H., O’Connor P.W., Havrdova E. et al.; AFFIRM Investigators: A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl. J. Med. 2006; 354(9): 899-910.
8. Rudick R.A., Stuart W.H., Calabresi P.A. et al.; SENTINEL Investigators: Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N. Engl. J. Med. 2006; 354(9): 911-923.
9. O’Connor P., Wolinsky J.S., Confavreux C. et al.; TEMSO Trial Group: Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N. Engl. J. Med. 2011; 365(14): 1293-1303.
10. Gold R., Kappos L., Arnold D.L. et al.; DEFINE Study Investigators: Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N. Engl. J. Med. 2012; 367(12): 1098-1107.
11. Fox R.J., Kita M., Cohan S.L. et al.: BG-12 (dimethyl fumarate): a review of mechanism of action, efficacy, and safety. Curr. Med. Res. Opin. 2014; 30(2): 251-262.
12. Cohen J.A., Coles A.J., Arnold D.L. et al.; CARE-MS I investigators: Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet 2012; 380(9856): 1819-1828.
13. Coles A.J., Twyman C.L., Arnold D.L. et al.; CARE-MS II investigators: Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet 2012; 380(9856): 1829-1839.
14. Polman C.H., Reingold S.C., Banwell B. et al.: Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann. Neurol. 2011; 69(2): 292-302.
15. Putzki N., Yaldizli O., Bühler R. et al.: Natalizumab reduces clinical and MRI activity in multiple sclerosis patients with high disease activity: results from a multicenter study in Switzerland. Eur. Neurol. 2010; 63(2): 101-106.
16. Prosperini L., Giannì C., Leonardi L. et al.: Escalation to natalizumab or switching among immunomodulators in relapsing multiple sclerosis. Mult. Scler. 2012; 18(1): 64-71.
17. Castillo-Trivino T., Mowry E.M., Gajofatto A. et al.: Switching multiple sclerosis patients with breakthrough disease to second-line therapy. PLoS One 2011; 6(2): e16664.
18. Krysko KM, O’Connor PW.: The Toronto observational study of natalizumab in multiple sclerosis. Can. J. Neurol. Sci. 2011; 38(3): 422-428.
19. Khatri B., Barkhof F., Comi G. et al.; TRANSFORMS Study Group: Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomised extension of the TRANSFORMS study. Lancet Neurol. 2011; 10(6): 520-529.
20. Freedman M.S., Selchen D., Arnold D.L. et al.; Canadian Multiple Sclerosis Working Group: Treatment optimization in MS: Canadian MS Working Group updated recommendations. Can. J. Neurol. Sci. 2013; 40(3): 307-323.
21. Río J., Castilló J., Rovira A. et al.: Measures in the first year of therapy predict the response to interferon beta in MS. Mult. Scler. 2009; 15(7): 848-853.
22. Romeo M., Martinelli V., Rodegher M. et al.; San Raffaele Multiple Sclerosis Clinical Group: Validation of 1-year predictive score of long-term response to interferon-β in everyday clinical practice multiple sclerosis patients. Eur. J. Neurol. 2015; 22(6): 973-980.
23. Sormani M.P., Río J., Tintorè M. et al.: Scoring treatment response in patients with relapsing multiple sclerosis. Mult. Scler. 2013; 19(5): 605-612.