Efficacy and Safety of FTY720 in the Treatment of Relapsing-Remitting Multiple Sclerosis: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

 BAO Chun ^1,2 , ZHOU Jianhua ¹

1. Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China;2. Chinese Medical Hospital of Xiangyan, Xiangyan 441000, China;

Corresponding author：

BAO Chun , Email: jhzhou@tjh.tjmu.edu.cn

Keywords：

FTY720; Multiple sclerosis/relapsing-remitting; Meta-analysis; Systematic review; Randomized controlled trial

DOI：

10.7507/1672-2531.20120071

Video：

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Objective 　To evaluate the efficacy and safety of FTY720 (fligolimod) in different dosages in the treatment of Relapsing-Remitting Multiple Sclerosis (RRMS), so as to provide references for clinical practice.
Methods 　 Such databases as MEDLINE, EMbase, The Cochrane Liabrary, CBM and CNKI were searched for collecting randomized controlled trials (RCTs) of FTY720 in the treatment of RRMS, which were published from January 1, 2001 to December 31, 2010. The studies were retrieved and the data were extracted according to the predefined inclusion and exclusion criteria, the quality of included studies was evaluated with improved Jadad scale, and the Meta-analyses were performed with RevMan5.1 software.
Results 　Three high quality RCTs were included. The Meta-analyses showed that: a) compared with the control group, orally taking FTY720 could obviously decreased the annualized relapse rate (OR=-6.67, 95%CI -10.75 to -2.60, P=0.001), the confirmed disability progression rate (OR=0.64, 95%CI 0.47 to 0.87, P=0.004), and the incidence rate of intensified lesion on T2-weighted magnetic resonance imaging scans (OR=0.28, 95%CI 0.21 to 0.37, P lt;0.00001); b) There was no significant difference (P=0.55) between the small dosage (0.5mg/d) group and the big dosage (1.25mg/d) group of FTY720; and c) The incidence of adverse events was significantly different among the 3 dosage groups (5mg/d, 1.25mg/d and 0.5mg/d), and the minimum dosage group (0.5mg/d) was safer than the other groups.
Conclusion 　FTY720 is safe to treat RRMS, and it can obviously decrease the annualized relapse rate, confirmed disability progression rate and incidence rate of intense lesion on T2-weighted magnetic resonance imaging scans. There is no dosage-effect relationship found in treating RRMS with FTY720 in different dosages, but the 0.5mg/d FTY720 as the minimum dosage is the safest.

Citation： BAO Chun ,ZHOU Jianhua. Efficacy and Safety of FTY720 in the Treatment of Relapsing-Remitting Multiple Sclerosis: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2012, 12(4): 445-450. doi: 10.7507/1672-2531.20120071 Copy

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2.	Cheng XJ, Xu LZ. Review of the diagnosis and clinical features of multiple sclerosis in China. Neurosci Bull, 2009, 25(1): 38-42 .
3.	Sanford M, Lyseng-Williamson KA. Subcutaneous recombinant interferon-β-1a (Rebif?): a review of its use in the treatment of relapsing multiple sclerosis. Drugs, 2011, 71(14): 1865-1891.
4.	Ravnborg M, Sørensen PS, Andersson M, et al. Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised,placebo-controlled, parallel-group trial. Lancet Neurol, 2010, 9(7): 672-680.
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6.	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.
7.	Belachew S, Phan-Ba R, Bartholomé E, et al. Natalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing-remitting multiple sclerosis. Eur J Neurol, 2011, 18(2): 240-245.
8.	Rommer PS, Patejdl R, Winkelmann A, et al. Rituximab for secondary progressive multiple sclerosis: a case series. CNS Drugs, 2011, 25(7): 607-613.
9.	Stein MS, Liu Y, Gray OM, et al. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology, 2011, 77(17): 1611-1618.
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11.	Fassas A, Kimiskidis VK, Sakellari I, et al. Long-term results of stem cell transplantation for MS: a single-center experience. Neurology, 2011, 76(12): 1066-1070.
12.	Matzke B, Metze C, Winkelmann A, et al. Severe relapse of multiple sclerosis during plasma exchange treatment. Mult Scler, 2011, 17(6): 759-762.
13.	Chun J, Hartung HP. Mechanism of action of oral Fingolimod (FTY720) in multiple sclerosis. Clinical Neuropharmacol, 2010, 33(2): 91-101.
14.	Horga A, Montalban X. FTY720 (fingolimod) for relapsing multiple sclerosis. Expert Rev Neurother, 2008, 8(5): 699-714.
15.	邓可刚. 循证医学证据的检索步骤与检索系统的选择. 中国循证医学杂志, 2004, 4(9): 634-637.
16.	郭新峰, 温泽淮, 老鹰荣, 等. 临床试验质量评价工具及其应用. 中国循证医学杂志, 2004, 4(7): 484-487.
17.	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.
18.	Kappos L, Radue EW, O’connor P, et al. A placebo-controlled trial of oral fingonimod in relapsing multiple Sclerosis. N Engl J Med, 2010, 362(5): 387-401.
19.	Kappos L, Antel J, Comi G, et al. Oral fingolimod (FTY720) for relapsing multiple Sclerosis. N Engl J Med, 2006, 355(11): 1124-1140.
20.	Cohen JA, Barkhof F, Comi G, et al. Oral Fingolimod or Intramuscular. Interferon for relapsing multiple Sclerosis. N Engl J Med, 2010, 362(10): 402-415.
21.	Comi G, O’connor P, Montalban X, et al. Phase Ⅱ study of oral fingolimod (FTY720) in multiple sclerosis:3-year results. Mult Scler, 2010, 16(2): 197-207.
22.	Doggrell SA. Is fingolimod an advancement in the treatment of multipie sclerosis? Expert Opin.Pharmacother, 2007, 8(3): 383-386.
23.	Brown BA, Kantesaria PP, McDevitt LM. Fingolimod: A Novel Immunosuppressant for Multiple sclerosis. Ann Pharmacother, 2007, 41(10): 1660-1668.
24.	Aktas O, Küry P, Kieseier B, et al. Fingolimod is a potential novel therapy for multiple sclerosis. Nat Rev Neurol, 2010, 6(7): 373-382.

1. Trojano M, Paolicelli D, Tortorella C, et al. Natural history of multiple sclerosis: have available therapies impacted long-term prognosis? Neurol Clin, 2011, 29(2): 309-321.
2. Cheng XJ, Xu LZ. Review of the diagnosis and clinical features of multiple sclerosis in China. Neurosci Bull, 2009, 25(1): 38-42 .
3. Sanford M, Lyseng-Williamson KA. Subcutaneous recombinant interferon-β-1a (Rebif?): a review of its use in the treatment of relapsing multiple sclerosis. Drugs, 2011, 71(14): 1865-1891.
4. Ravnborg M, Sørensen PS, Andersson M, et al. Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised,placebo-controlled, parallel-group trial. Lancet Neurol, 2010, 9(7): 672-680.
5. Vollmer T, Panitch H, Bar-Or A, et al. Glatiramer acetate after induction therapy with mitoxantrone in relapsing multiple sclerosis. Mult Scler, 2008, 14 (5): 663-670.
6. 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.
7. Belachew S, Phan-Ba R, Bartholomé E, et al. Natalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing-remitting multiple sclerosis. Eur J Neurol, 2011, 18(2): 240-245.
8. Rommer PS, Patejdl R, Winkelmann A, et al. Rituximab for secondary progressive multiple sclerosis: a case series. CNS Drugs, 2011, 25(7): 607-613.
9. Stein MS, Liu Y, Gray OM, et al. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology, 2011, 77(17): 1611-1618.
10. Papadopoulos D, Mitsikostas DD. Nocebo effects in multiple sclerosis trials: a meta-analysis. Mult Scler, 2010 , 16(7): 816-828.
11. Fassas A, Kimiskidis VK, Sakellari I, et al. Long-term results of stem cell transplantation for MS: a single-center experience. Neurology, 2011, 76(12): 1066-1070.
12. Matzke B, Metze C, Winkelmann A, et al. Severe relapse of multiple sclerosis during plasma exchange treatment. Mult Scler, 2011, 17(6): 759-762.
13. Chun J, Hartung HP. Mechanism of action of oral Fingolimod (FTY720) in multiple sclerosis. Clinical Neuropharmacol, 2010, 33(2): 91-101.
14. Horga A, Montalban X. FTY720 (fingolimod) for relapsing multiple sclerosis. Expert Rev Neurother, 2008, 8(5): 699-714.
15. 邓可刚. 循证医学证据的检索步骤与检索系统的选择. 中国循证医学杂志, 2004, 4(9): 634-637.
16. 郭新峰, 温泽淮, 老鹰荣, 等. 临床试验质量评价工具及其应用. 中国循证医学杂志, 2004, 4(7): 484-487.
17. 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.
18. Kappos L, Radue EW, O’connor P, et al. A placebo-controlled trial of oral fingonimod in relapsing multiple Sclerosis. N Engl J Med, 2010, 362(5): 387-401.
19. Kappos L, Antel J, Comi G, et al. Oral fingolimod (FTY720) for relapsing multiple Sclerosis. N Engl J Med, 2006, 355(11): 1124-1140.
20. Cohen JA, Barkhof F, Comi G, et al. Oral Fingolimod or Intramuscular. Interferon for relapsing multiple Sclerosis. N Engl J Med, 2010, 362(10): 402-415.
21. Comi G, O’connor P, Montalban X, et al. Phase Ⅱ study of oral fingolimod (FTY720) in multiple sclerosis:3-year results. Mult Scler, 2010, 16(2): 197-207.
22. Doggrell SA. Is fingolimod an advancement in the treatment of multipie sclerosis? Expert Opin.Pharmacother, 2007, 8(3): 383-386.
23. Brown BA, Kantesaria PP, McDevitt LM. Fingolimod: A Novel Immunosuppressant for Multiple sclerosis. Ann Pharmacother, 2007, 41(10): 1660-1668.
24. Aktas O, Küry P, Kieseier B, et al. Fingolimod is a potential novel therapy for multiple sclerosis. Nat Rev Neurol, 2010, 6(7): 373-382.

Chinese Journal of Evidence-Based Medicine

Efficacy and Safety of FTY720 in the Treatment of Relapsing-Remitting Multiple Sclerosis: A Systematic Review

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