Fingolimod therapy for multiple sclerosis

Seminars in Neurology

Volumn 33, Issue 1, 2013, Pages 37-44

  Willis, Mary A ^a   Cohen, Jeffrey A ^a  

^a LERNER RESEARCH INSTITUTE   (United States)

Author keywords

fingolimod; multiple sclerosis; sphingosine 1 phosphate; therapy

Indexed keywords

ALEMTUZUMAB; BETA1A INTERFERON; FINGOLIMOD; GADOLINIUM; NATALIZUMAB; PLACEBO; RITUXIMAB; SPHINGOSINE 1 PHOSPHATE RECEPTOR;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; ATRIOVENTRICULAR CONDUCTION; BACKACHE; BILIRUBIN BLOOD LEVEL; BRADYCARDIA; BRAIN SIZE; CENTRAL NERVOUS SYSTEM; CLINICAL PRACTICE; COUGHING; DIARRHEA; DISEASE COURSE; DRUG CLEARANCE; DRUG CONTRAINDICATION; DRUG DOSE COMPARISON; DRUG EFFECT; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG METABOLISM; DRUG SAFETY; DRUG SUBSTITUTION; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPNEA; FORCED EXPIRATORY VOLUME; HUMAN; IMMUNOMODULATION; INFECTION RISK; INFLUENZA; LUNG DIFFUSION CAPACITY; LYMPHOCYTE COUNT; LYMPHOCYTOPENIA; MULTIPLE SCLEROSIS; NUCLEAR MAGNETIC RESONANCE IMAGING; PATIENT MONITORING; PATIENT SELECTION; PHASE 2 CLINICAL TRIAL (TOPIC); PHYSICAL DISABILITY; POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME; POSTMARKETING SURVEILLANCE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RELAPSE; RETINA MACULA EDEMA; SIDE EFFECT; VASOSPASM;

CENTRAL NERVOUS SYSTEM; HUMANS; IMMUNOSUPPRESSIVE AGENTS; LYSOPHOSPHOLIPIDS; MULTIPLE SCLEROSIS; PROPYLENE GLYCOLS; SPHINGOSINE; TREATMENT OUTCOME;

EID: 84878311049     PISSN: 02718235     EISSN: 10989021     Source Type: Journal    
DOI: 10.1055/s-0033-1343794     Document Type: Article

References (46)

1. Chun J., Hartung H. P. Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clin Neuropharmacol: 2010; 33 2 91 101
2. Cohen J. A., Chun J. Mechanisms of fingolimod's efficacy and adverse effects in multiple sclerosis. Ann Neurol: 2011; 69 5 759 777
3. Mehling M., Johnson T. A., Antel J., Kappos L., Bar-Or A. Clinical immunology of the sphingosine 1-phosphate receptor modulator fingolimod (FTY720) in multiple sclerosis. Neurology: 2011; 76 8 03 S20 S27
4. Mehling M. KL, Kappos L., Derfuss T. Fingolimod for multiple sclerosis: mechanism of action, clinical outcomes, and future directions. Curr Neurol Neurosci Rep: 2011; 11 5 492 497
5. Gräler M. HGE, Goetzl E. J. The immunosuppressant FTY720 down-regulates sphingosine 1-phosphate G-protein-coupled receptors. FASEB J: 2004; 18 3 551 553
6. Mehling M. BV, Brinkmann V., Antel J., et al. FTY720 therapy exerts differential effects on T cell subsets in multiple sclerosis. Neurology: 2008; 71 16 1261 1267
7. Brinkmann V., Billich A., Baumruker T., et al. Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov: 2010; 9 11 883 897
8. Dev K. K., Mullershausen F., Mattes H., et al. Brain sphingosine-1- phosphate receptors: implication for FTY720 in the treatment of multiple sclerosis. Pharmacol Ther: 2008; 117 1 77 93 (Pubitemid 350192672)
9. Foster C. A., Howard L. M., Schweitzer A., et al. 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 2 469 475
10. Miron V. E., Schubart A., Antel J. P. Central nervous system-directed effects of FTY720 (fingolimod). J Neurol Sci: 2008; 274 1-2 13 17
11. Coelho R. P., Payne S. G., Bittman R., Spiegel S., Sato-Bigbee C. The immunomodulator FTY720 has a direct cytoprotective effect in oligodendrocyte progenitors. J Pharmacol Exp Ther: 2007; 323 2 626 635 (Pubitemid 350005137)
12. Kovarik J. M., Hartmann S., Bartlett M., et al. Oral-intravenous crossover study of fingolimod pharmacokinetics, lymphocyte responses and cardiac effects. Biopharm Drug Dispos: 2007; 28 2 97 104 (Pubitemid 46455770)
13. Kovarik J. M., Schmouder R., Barilla D., Wang Y., Kraus G. Single-dose FTY720 pharmacokinetics, food effect, and pharmacological responses in healthy subjects. Br J Clin Pharmacol: 2004; 57 5 586 591 (Pubitemid 38582178)
14. Warnke C., Stüve O., Hartung H. P., Fogdell-Hahn A., Kieseier B. C. Critical appraisal of the role of fingolimod in the treatment of multiple sclerosis. Neuropsychiatr Dis Treat: 2011; 7 519 527
15. Kappos L., Antel J., Comi G., et al. FTY720 D2201 Study Group Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med: 2006; 355 11 1124 1140 (Pubitemid 44394919)
16. 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
17. Cohen J. A., Barkhof F., Comi G., et al. TRANSFORMS Study Group Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med: 2010; 362 5 402 415
18. Kappos L., Radue E-W, O' Connor P., et al. Long-term efficacy and safety of fingolimod (FTY720) in relapsing-remitting multiple sclerosis (RRMS): results from the extension of the phase III FREEDOMS study. Paper presented at: Annual Meeting of the American Academy of Neurology; April 26, 2012; New Orleans, LA
19. Antel J., Montalban X., O'Connor P., et al. Long-term (7-year) data from a phase 2 extension study of fingolimod in relapsing multiple sclerosis. Paper presented at: Annual Meeting of the American Academy of Neurology; April 23, 2012; New Orleans, LA
20. Johnson T. A., Shames I., Keezer M., et al. Reconstitution of circulating lymphocyte counts in FTY720-treated MS patients. Clin Immunol: 2010; 137 1 15 20
21. U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER). Fingolimod Background Package (NDA 22-257). Available at: http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/ drugs/peripheralandcentralnervoussystemdrugsadvisorycommittee/ucm216553.pdf. Accessed May 6, 2012
22. Collins W., Cohen J., O' Connor P., et al. Long-term safety of oral fingolimod (FTY720) in relapsing multiple sclerosis: integrated analyses of phase 1 and phase 3 studies (P843). Mult Scler: 2010; 16 10 S295
23. Schmouder R., Serra D., Wang Y., et al. FTY720: placebo-controlled study of the effect on cardiac rate and rhythm in healthy subjects. J Clin Pharmacol: 2006; 46 8 895 904 (Pubitemid 44050826)
24. DiMarco J. P., O'Connor P., Cohen J. A., et al. First-dose effect of fingolimod: pooled safety data from two phase 3 studies (TRANSFORMS and FREEDOMS). Mult Scler: 2010; 16 10 S290
25. Espinosa P. S., Berger J. R. Delayed fingolimod-associated asystole. Mult Scler: 2011; 17 11 1387 1389
26. U.S. Food and Drug Administration FDA Drug Safety Communication: Safety Review of a Reported Death after the First Dose of Multiple Sclerosis Drug Gilenya (Fingolimod). Available at: http://www.fda.gov/Drugs/DrugSafety/ ucm284240.htm. Accessed May 6, 2012
27. Salvadori M., Budde K., Charpentier B., et al. FTY720 0124 Study Group FTY720 versus MMF with cyclosporine in de novo renal transplantation: a 1-year, randomized controlled trial in Europe and Australasia. Am J Transplant: 2006; 6 12 2912 2921
28. Jain N., Bhatti M. T. Fingolimod-associated macular edema: incidence, detection, and management. Neurology: 2012; 78 9 672 680
29. U.S. Food and Drug Administration FDA Approved Labeling Text for GILENYA (Fingolimod) Capsules (NDA 02257). Updated April 2012. Washington, DC U.S. Food and Drug Administration
30. ONE Neuro-Ophthalmology Committee Oral MS Drug May Increase Risk for Macular Edema: A Report from the North American Neuro-Ophthalmology Society (NANOS) and the AAO. Released September 10, 2011. Available at: http://www.nanosweb.org/files/public/MS-drug-may-increase-risk-for- RVO1NOTRACK2lf.pdf. Accessed May 6, 2012
31. Novartis. Gilenya (Finglimod) Safety Information Update (Released April 13, 2012). Available at: http://www.novartis.com/downloads/newsroom/product- related-info-center/statement-PML.pdf. Accessed May 15, 2012
32. Francis G. S., Kappos L., O' Connor P., et al. Lymphocytes and fingolimod-temporal pattern and relationship with infections. Mult Scler: 2010; 16 Suppl 10 S146
33. Ontaneda D., Cohen J. A. Potential mechanisms of efficacy and adverse effects in the use of fingolimod (FTY720). Expert Rev Clin Pharmacol: 2011; 4 5 567 570
34. Schwarz A., Korporal M., Hosch W., Max R., Wildemann B. Critical vasospasm during fingolimod (FTY720) treatment in a patient with multiple sclerosis. Neurology: 2010; 74 24 2022 2024
35. Pfaff M., Powaga N., Akinci S., et al. Activation of the SPHK/S1P signalling pathway is coupled to muscarinic receptor-dependent regulation of peripheral airways. Respir Res: 2005; 6 48
36. Brinkmann V., Baumruker T. Pulmonary and vascular pharmacology of sphingosine 1-phosphate. Curr Opin Pharmacol: 2006; 6 3 244 250 (Pubitemid 44274746)
37. Collins W., Francis G., Koren G., et al. Lack of interaction between fingolimod (FTY720) and oral contraceptives, and pregnancy experience in the clinical program of fingolimod in multiple sclerosis. Paper presented at: Annual Meeting of the American Academy of Neurology; April 9, 2011; Honolulu, HI
38. Castrop F., Kowarik M. C., Albrecht H., et al. Severe multiple sclerosis relapse under fingolimod therapy: incident or coincidence? Neurology: 2012; 78 12 928 930
39. Min J-H, Kim B. J., Lee K. H. Development of extensive brain lesions following fingolimod (FTY720) treatment in a patient with neuromyelitis optica spectrum disorder. Mult Scler: 2012; 18 1 113 115
40. Havla J. B., Pellkofer H. L., Meinl I., Gerdes L. A., Hohlfeld R., Kümpfel T. Rebound of disease activity after withdrawal of fingolimod (FTY720) treatment. Arch Neurol: 2012; 69 2 262 264
41. Pelletier D., Hafler D. A. Fingolimod for multiple sclerosis. N Engl J Med: 2012; 366 4 339 347
42. Novartis. FTY720 in Patients With Primary Progressive Multiple Sclerosis. ClinicalTrials.gov Identifier: NCT00731692. Available at: http:// ClinicalTrials.gov/show/NCT00731692. Accessed May 15, 2012
43. Novartis. Disease Control and Safety in Patients With Relapsing Remitting Multiple Sclerosis (RRMS) Switching From Natalizumab to Fingolimod. ClinicalTrials.gov Identifier: NCT01499667. Available at: http://ClinicalTrials. gov/show/NCT01499667. Accessed May 15, 2012
44. GlaxoSmithKline A Study to Assess the Relative Bioavailability of Different Formulations of GSK2018682, a Sphingosine-1-Phosphate Receptor Subtype 1 Agonist, in Healthy Volunteers. ClinicalTrials.gov Identifier: NCT01466322. Available at: http://ClinicalTrials.gov/show/NCT01466322. Accessed May 15, 2012
45. Novartis. Safety, Tolerability, Efficacy and Optimal Dose Finding Study of BAF312 in Patients With Relapsing-Remitting Multiple Sclerosis. ClinicalTrials.gov Identifier: NCT00879658. Available at: http://ClinicalTrials. gov/show/NCT00879658. Accessed May 15, 2012
46. Ono Pharma A Study of the Safety and Efficacy of ONO-4641 in Patients With Relapsing-Remitting Multiple Sclerosis. ClinicalTrials.gov Identifier: NCT01081782. Available at: http://ClinicalTrials.gov/show/NCT01081782. Accessed May 15, 2012