Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis

BİRDAY, Erkingül; ALTUNRENDE, Burcu; Akman-Demir, Gulsen; KASAP, Mithat

Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis

Burcu ALTUNRENDE, (İstanbul Bilim Üniversitesi Tıp Fakültesi Hastanesi, Nöroloji Anabilim Dalı, İstanbul, Türkiye)

Erkingül BİRDAY, (Medipol Mega Üniversitesi Hastanesi, Nöroloji Anabilim Dalı, İstanbul, Türkiye)

Mithat KASAP, (Novartis Farma, İstanbul, Türkiye)

Gülşen Akman DEMİR (İstanbul Bilim Üniversitesi Tıp Fakültesi Hastanesi, Nöroloji Anabilim Dalı, İstanbul, Türkiye)

Türk Nöroloji Dergisi

15 2

Yıl: 2017 Cilt: 23 Sayı: 4 Sayfa Aralığı: 176 - 185 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis

Öz:

Multipl skleroz (MS) merkezi sinir sisteminin enflamasyon, demiyelinizasyon ve akson kaybı ile karakterize kronik otoimmün, nörodejeneratif bir hastalığıdır. Fingolimod Amerikan İlaç ve Gıda Dairesi ve Avrupa Birliği üyesi ülkelerin de bulunduğu 80'den fazla ülke tarafından onaylanmış ilk oral MS ilacıdır. Bu bileşik, sfingozin-1 fosfat olarak bilinen lizofosfolipid reseptörleri aracılığı ile etkilerini gösterir. Günlük oral yolla kullanımı kolaylık sağlamakla birlikte bazı hastalarda ilk doz sırasında bradikardi gelişmesi, maküler ödem, enfeksiyon gibi bazı dikkat edilmesi gereken durumlar ile karşılaşılabilmektedir. Randomize çift-kör klinik çalışmalar, plasebo ve intramüsküler interferon ?-1a tedavilerine kıyasla fingolimodun atak sıklığını anlamlı derecede azalttığını ve beyin manyetik rezonans ölçütleri üzerine yararlı etkiler gösterdiğini ortaya koymuştur. Bu derlemede, fingolimodun klinikte MS hastalarının yönetimindeki etkinliği, güvenliliği ve tolerabilitesi ele alınmıştır

Anahtar Kelime:

Konular: Nörolojik Bilimler

Relapsing Remitting Multipl Skleroz Tedavisinde Fingolimod Kullanımı

Öz:

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system and is characterized by inflammation, demyelination, and axonal loss. Fingolimod is the first oral drug for the treatment of MS approved by the United States Food and Drug Administration, European Union countries, and various other countries. The compound exerts its effect via interaction with lysophospholipid receptors known as sphingosine-1 phosphate receptors. Although fingolimod has a very convenient daily oral dosing, it may cause development of bradycardia at the first dose, macular edema, infection, all of which require attention. Randomized double-blind clinical trials have shown that fingolimod significantly reduces relapse rates and is beneficial in brain magnetic resonance imaging measures when compared with both placebo and intramuscular interferon β-1a. This review describes the characteristics of fingolimod concerning its efficacy, safety, and tolerability in the clinical context of the management of MS

Anahtar Kelime:

Konular: Nörolojik Bilimler

Belge Türü: Makale Makale Türü: Derleme Erişim Türü: Erişime Açık

1. Compston A, Coles A. Multiple sclerosis. Lancet 2008;372:1502-1517.
2. Hauser SL, Goodin DS. Multiple Sclerosis and Other Demyelinating Diseases. In: Longo D, Fauci AS, Kasper DL, Hauser S, Jameson JL, Loscalzo J (eds). Harrison’s Principles of Internal Medicine. 18th ed. McGraw-Hill Global Education Holdings, LLC, 2012:33.
3. 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;46:907-911.
4. Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors. Ann Neurol 2007;61:504-513.
5. No authors listed. Randomised double-blind plasebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet 1998;352:1498-1504.
6. Mehling M, Johnson TA, Antel J, Kappos L, Bar-Or A. Clinical immunology of the sphingosine 1-phosphate receptor modulator fingolimod (FTY720) in multiple sclerosis. Neurology 2011;76(Suppl 3):20-27.
7. Brinkmann V, Billich A, Baumruker T, Heining P, Schmouder R, Francis G, Aradhye S, Burtin P. Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov 2010;9:883-897.
8. Chiba K, Hoshino Y, Suzuki C, Masubuchi Y, Yanagawa Y, Ohtsuki M, Sasaki S, Fujita T. FTY720, a novel immunosuppressant possessing unique mechanisms. I. Prolongation of skin allograft survival and synergistic effect in combination with cyclosporine in rats. Transplant Proc 1996;28:1056-1059.
9. Webb M, Tham CS, Lin FF, Lariosa-Willingham K, Yu N, Hale J, Mandala S, Chun J, Rao TS. Sphingosine 1-phosphate receptor agonists attenuate relapsing-remitting experimental autoimmune encephalitis in SJL mice. J Neuroimmunol 2004;153:108-121.
10. Mandala S, Hajdu R, Bergstrom J, Quackenbush E, Xie J, Milligan J, Thornton R, Shei GJ, Card D, Keohane C, Rosenbach M, Hale J, Lynch CL, Rupprecht K, Parsons W, Rosen H. Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science 2002;296:346-349.
11. Foster CA, Howard LM, Schweitzer A, Persohn E, Hiestand PC, Balatoni B, Reuschel R, Beerli C, Schwartz M, Billich A. Brain penetration of the oral immunomodulatory drug FTY720 and its phosphorylation in the central nervous system during experimental autoimmune encephalomyelitis: consequences for mode of action in multiple sclerosis. J Pharmacol Exp Ther 2007;323:469-475.
12. Di Menna L, Molinaro G, Di Nuzzo L, Riozzi B, Zappulla C, Pozzilli C, Turrini R, Caraci F, Copani A, Battaglia G, Nicoletti F, Bruno V. Fingolimod protects cultured cortical neurons against excitotoxic death. Pharmacol Res 2013;67:1-9.
13. Balatoni B, Storch MK, Swoboda EM, Schönborn V, Koziel A, Lambrou GN, Hiestand PC, Weissert R, Foster CA. FTY720 sustains and restores neuronal function in the DA rat model of MOG-induced experimental autoimmune encephalomyelitis. Brain Res Bull 2007;74:307-316.
14. Kappos L, Radue EW, O’Connor P, Polman C, Hohlfeld R, Calabresi P, Selmaj K, Agoropoulou C, Leyk M, Zhang-Auberson L, Burtin P; FREEDOMS Study Group. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010;362:387-401.
15. Calabresi PA, Radue EW, Goodin D, Jeffery D, Rammohan KW, Reder AT, Vollmer T, Agius MA, Kappos L, Stites T, Li B, Cappiello L, von Rosenstiel P, Lublin FD. Safety and efficacy of fingolimod in patients with relapsingremitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Neurol 2014;13:545-556.
16. Cohen JA, Barkhof F, Comi G, Hartung HP, Khatri BO, Montalban X, Pelletier J, Capra R, Gallo P, Izquierdo G, Tiel-Wilck K, de Vera A, Jin J, Stites T, Wu S, Aradhye S, Kappos L; TRANSFORMS Study Group. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010;362:402-415.
17. Derfuss T, Ontaneda D, Nicholas J, Meng X, Hawker K. Relapse rates in patients with multiple sclerosis treated with fingolimod: Subgroup analyses of pooled data from three phase 3 trials. Mult Scler Relat Disord 2016;8:124-130.
18. Bergvall N, Sfikas N, Chin P, Tomic D, von Rosenstiel P, Alsop J, Cutter G, Calabresi P, Jeffery D, Lublin F, Kappos L. Effect of Fingolimod on Disability Progression in Multiple Sclerosis Patients With and Without Disability at Baseline: Post Hoc Analyses of FREEDOMS and FREEDOMS II. Poster presented at the 65th American Academy of Neurology (AAN) Annual Meeting 2013:P04;128.
19. Sfikas N, Bergvall N, Chin P, Tomic D, von Rosenstiel P, Alsop J, Cutter G, Calabresi P, Jeffery D, Lublin F, Kappos L. Effect of Fingolimod on Clinical and Magnetic Resonance Imaging Outcomes in Multiple Sclerosis Patients with no Disability at Baseline: Post Hoc Analyses of FREEDOMS and FREEDOMS II. Poster presented at the 65th American Academy of Neurology (AAN) Annual Meeting 2013:P07;124.
20. Radue EW, O’Connor P, Polman CH, Hohlfeld R, Calabresi P, Selmaj K, Mueller-Lenke N, Agoropoulou C, Holdbrook F, de Vera A, Zhang-Auberson L, Francis G, Burtin P, Kappos L; FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS) Study Group. Impact of fingolimod therapy on magnetic resonance imaging outcomes in patients with multiple sclerosis. Arch Neurol 2012;69:1259-1269.
21. Cohen J, Radue EW, Barkhof F, Kappos L, Calabresi P, Häring DA, Sfikas N, von Rosenstiel P, Francis G. Fingolimod-effect on brain atrophy and clinical/ MRI correlations in three phase 3 studies - TRANSFORMS, FREEDOMS and FREEDOMS II. American Academy of Neurology (AAN) 2013:S51.006.
22. Fernandez O. Best practice in the use of natalizumab in multiple sclerosis. Ther Adv Neurol Disord 2013;6:69-79.
23. Totaro R, Di Carmine CD, Costantino G, Fantozzi R, Bellantonio P, Fuiani A, Mundi C, Ruggieri S, Marini C, Carolei A. Fingolimod treatment in relapsing-remitting multiple sclerosis patients: a prospective observational multicenter postmarketing study. Mult Scler Int 2015;2015:763418.
24. Ziemssen T, Albrecht H, Haas J, Klotz L, Lang M, Lassek C, Schmidt S, Tackenberg B, Cornelissen C. 4 years PANGAEA: effectiveness update of a 5 year non-interventional study on the daily use of fingolimod in Germany. 32nd ed. Congress of the European Committee for Treatment and Research in Multiple Sclerosis; London, United Kingdom, 2016:14-17.
25. Ziemssen T, Vollmar P, Diaz-Lorente M, Fuchs A, van Lokven T. 18-month interim results of a registry study to establish long-term safety and pharmacoeconomic data on fingolimod (Gilenya®) in multiple sclerosis patients in Germany (PANGAEA). 29th ed. Congress of the European Committee for Treatment and Research in Multiple Sclerosis; Copenhagen, Denmark, 2013:2-5.
26. Spelman T, Bergvall N, Tomic D, Trojano M, Izquierdo G, Lugaresi A, Alroughani R, Grammond P, Grand’Maison F, Duquette P, Havrdova E, Lechner-Scott J, Verheul F, Butzkueven H. Real-world comparative effectiveness of fingolimod and interferon/glatiramer therapies in a switch population using propensity-matched data from MSBase. Mult Scler 2013;19(Suppl 1):514.
27. He A, Spelman T, Jokubaitis V, Havrdova E, Horakova D, Trojano M, Lugaresi A, Izquierdo G, Grammond P, Duquette P, Girard M, Pucci E, Iuliano G, Alroughani R, Oreja-Guevara C, Fernandez-Bolaños R, Grand’Maison F, Sola P, Spitaleri D, Granella F, Terzi M, Lechner-Scott J, Van Pesch V, Hupperts R, Sánchez-Menoyo JL, Hodgkinson S, Rozsa C, Verheul F, Butzkueven H, Kalincik T; MSBase Study Group. Comparison of switch to fingolimod or interferon beta/glatiramer acetate in active multiple sclerosis. JAMA Neurol 2015;72:405-413.
28. Yamout BI, Zeineddine MM, Tamim H, Khoury SJ. Safety and efficacy of fingolimod in clinical practice: The experience of an academic center in the Middle East. J Neuroimmunol 2015;289:93-97.
29. Terzi M, Kurtuncu M, Eraksoy M, Karabudak R, Tuncer A, Altunrende B, Akcalı A, Boz C, Sevim S, Nur Y, Tamam Y, Bitnel M, Turan OF, Soysal A, Ozerden M, Terzi Y. Real-life data from efficacy of fingolimod treatment in multiple sclerosis patients in Turkey, P651, Poster presented at the 32nd ed. Congress of the European Committee for Treatment and Research in Multiple Sclerosis; London, United Kingdom, 2016:14-17.
30. Mazurais D, Robert P, Gout B, Berrebi-Bertrand I, Laville MP, Calmels T. Cell type-specific localization of human cardiac S1P receptors. J Histochem Cytochem 2002;50:661-670.
31. Limmroth V, Haverkamp W, Dechend R, Lang M, Haas J, Wagner B, Richter S, Schieb H, Ziemssen T. Interim analysis of the START study - extensive electrocardiographic monitoring confirms the good cardiac safety profile of Fingolimod. ECTRIMS; Barcelona, Spain, 2015:7-10.
32. DiMarco JP, O’Connor P, Cohen JA, Reder AT, Zhang-Auberson L, Tang D, Collins W, Kappos L. First-dose effect of fingolimod: pooled safety data from three phase 3 studies. Mult Scler Rel Dis 2014;3:629-638.
33. Gold R, Comi G, Palace J, Siever A, Gottschalk R, Bijarnia M, von Rosenstiel P, Tomic D, Kappos L; FIRST Study Investigators. Assessment of cardiac safety during fingolimod treatment initiation in a real-world relapsing multiple sclerosis population: a phase 3b, open-label study. J Neurol 2014;261:267-276.
34. Singleton PA, Dudek SM, Ma SF, Garcia JG. Transactivation of sphingosine 1-phosphate receptors is essential for vascular barrier regulation. Novel role for hyaluronan and CD44 receptor family. J Biol Chem 2006;281:34381- 34393.
35. Zarbin MA, Jampol LM, Jager RD, Reder AT, Francis G, Collins W, Tang D, Zhang X. Ophthalmic evaluations in clinical studies of fingolimod (FTY720) in multiple sclerosis. Ophthalmology 2013;120:1432-1439.
36. Fingya Kısa Ürün Bilgisi (26.08.2016). Accessed date: 2016 Oct 9. Available from: https://www.novartis.com.tr/sites/www.novartis.com.tr/ files
37. Francis G, Kappos L, O’Connor P, Collins W, Tang D, Mercier F, Cohen JA. Temporal profile of lymphocyte counts and relationship with infections with fingolimod therapy. Mult Scler 2014;20:471-480.
38. Henault D, Galleguillos L, Moore C, Johnson T, Bar-Or A, Antel J. Basis for fluctuations in lymphocyte counts in fingolimod-reated patients with multiple sclerosis. Neurology 2013;81:1768-1772.
39. Novartis data on file (Data as of 31st May 2016).
40. Jokubaitis VG, Li V, Kalincik T, Izquierdo G, Hodgkinson S, Alroughani R, Lechner Scott J, Lugaresi A, Duquette P, Girard M, Barnett M, Grand’Maison F, Trojano M, Slee M, Giuliani G, Shaw C, Boz C, Spitaleri DL, Verheul F, Haartsen J, Liew D, Butzkueven H; MSBase Study Group. Fingolimod after natalizumab and the risk of short-term relapse. Neurology 2014;82:1204- 1211.
41. Ziemssen T, Albrecht H, Haas J, Klotz L, Lang M, Lassek C, Schmidt S, Tackenberg B, Cornelissen C. 4 Years PANGAEA: Long Term Data on Effectiveness and Safety from Patients on Natalizumab Switching to Fingolimod in Real World (P6.188). Neurology 2016:86(Suppl);16.
42. Mallada JJ, Barrero F, Martínez M, Marzo E, Meca VM, Ricart FJ, Garcia E. Interim Analysis Results of an Observational, Retrospective, Multicenter Study to Assess the Effectiveness of Fingolimod Treatment in Clinical Practice in Patients with Relapsing-Remitting Multiple Sclerosis in Spain: The NEXT Study (P3.096). Neurology 2016:86(Suppl);16.
43. Hatcher SE, Waubant E, Nourbakhsh B, Crabtree-Hartman E, Graves JS. Rebound syndrome in patients with multiple sclerosis after cessation of fingolimod treatment. JAMA Neurol 2016;73:790-794.
44. Kovarik JM, Lu M, Riviere GJ, Barbet I, Maton S, Goldwater DR, Schmouder RL. The effect on heart rate of combining single-dose fingolimod with steady-state atenolol or diltiazem in healthy subjects. Eur J Clin Pharmacol 2008;64:457-463.
45. Cohen J, Pradhan A, Gottschalk R, Chen Y, Kappos L. Ongoing safety and effectiveness: An interim analysis of long-term fingolimod treatment. Poster 3.057 presented at the 68th Congress of the American Academy of Neurology; Vancouver, Canada, 2016:15-21.
46. Khatri BO. Fingolimod in the treatment of relapsing-remitting multiple sclerosis: long-termexperience and an update on the clinical evidence. Ther Adv Neurol Disord 2016;9:130-147.
47. Radue EW, Barkhof F, Cohen J, Gottschalk R, Zhang Y, Cappiello L, von Rosenstiel P, Kappos L. Sustained low rate of brain volume loss under longterm fingolimod treatment in relapsing multiple sclerosis: results from the LONGTERMS study. Mult Scler 2014;20(Suppl 1):67-284.
48. Summary of opinion1 (post authorisation). Gilenya Fingolimod. Accessed date: 09.11.2016. Available from: http://www.ema.europa.eu/docs/en_GB/ document_library/Summary_of_opinion/human/002202/WC500194180.pdf
49. Gajofatto A, Benedetti MD. Treatment strategies for multiple sclerosis: when to start, when to change, when to stop? World J Clin Cases 2015;3:545-555.

APA	ALTUNRENDE B, BİRDAY E, KASAP M, Akman-Demir G (2017). Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis. , 176 - 185.
Chicago	ALTUNRENDE Burcu,BİRDAY Erkingül,KASAP Mithat,Akman-Demir Gulsen Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis. (2017): 176 - 185.
MLA	ALTUNRENDE Burcu,BİRDAY Erkingül,KASAP Mithat,Akman-Demir Gulsen Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis. , 2017, ss.176 - 185.
AMA	ALTUNRENDE B,BİRDAY E,KASAP M,Akman-Demir G Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis. . 2017; 176 - 185.
Vancouver	ALTUNRENDE B,BİRDAY E,KASAP M,Akman-Demir G Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis. . 2017; 176 - 185.
IEEE	ALTUNRENDE B,BİRDAY E,KASAP M,Akman-Demir G "Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis." , ss.176 - 185, 2017.
ISNAD	ALTUNRENDE, Burcu vd. "Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis". (2017), 176-185.

APA	ALTUNRENDE B, BİRDAY E, KASAP M, Akman-Demir G (2017). Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis. Türk Nöroloji Dergisi, 23(4), 176 - 185.
Chicago	ALTUNRENDE Burcu,BİRDAY Erkingül,KASAP Mithat,Akman-Demir Gulsen Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis. Türk Nöroloji Dergisi 23, no.4 (2017): 176 - 185.
MLA	ALTUNRENDE Burcu,BİRDAY Erkingül,KASAP Mithat,Akman-Demir Gulsen Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis. Türk Nöroloji Dergisi, vol.23, no.4, 2017, ss.176 - 185.
AMA	ALTUNRENDE B,BİRDAY E,KASAP M,Akman-Demir G Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis. Türk Nöroloji Dergisi. 2017; 23(4): 176 - 185.
Vancouver	ALTUNRENDE B,BİRDAY E,KASAP M,Akman-Demir G Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis. Türk Nöroloji Dergisi. 2017; 23(4): 176 - 185.
IEEE	ALTUNRENDE B,BİRDAY E,KASAP M,Akman-Demir G "Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis." Türk Nöroloji Dergisi, 23, ss.176 - 185, 2017.
ISNAD	ALTUNRENDE, Burcu vd. "Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis". Türk Nöroloji Dergisi 23/4 (2017), 176-185.