Patient experience and practice trends in multiple sclerosis – Clinical utility of fingolimod

Patient Preference and Adherence

Volumn 9, Issue , 2015, Pages 685-693

  Lee, Jong Mi ^a   Han, May H ^a,b  

^a STANFORD UNIVERSITY MEDICAL CENTER   (United States)

^b STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

FREEDOMS; IFN ; RRMS; Side effects; Sphingosine 1 phosphate; TRANSFORMS

Indexed keywords

BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BETA INTERFERON; BETA1A INTERFERON; CALCIUM CHANNEL BLOCKING AGENT; CHLORPROMAZINE; CITALOPRAM; DIGOXIN; DILTIAZEM; ERYTHROMYCIN; FINGOLIMOD; GLATIRAMER; HALOPERIDOL; METHADONE; NATALIZUMAB; PLACEBO; SPHINGOSINE 1 PHOSPHATE; VERAPAMIL;

BASAL CELL CARCINOMA; BOWEN DISEASE; BRADYCARDIA; BREAST CANCER; BREAST METASTASIS; BRONCHITIS; CARDIOTOXICITY; CARDIOVASCULAR DISEASE; CLINICAL PRACTICE; DIZZINESS; DRUG EFFICACY; DRUG MECHANISM; DRUG SUBSTITUTION; DRUG TARGETING; DRUG USE; FATIGUE; FIRST DEGREE ATRIOVENTRICULAR BLOCK; HEADACHE; HEART ARRHYTHMIA; HEART MUSCLE CONDUCTION DISTURBANCE; HEART PALPITATION; HERPES ZOSTER; HERPES ZOSTER ENCEPHALITIS; HUMAN; HYPERTENSION; INFECTION; INFECTION RISK; INFLUENZA; LUNG DISEASE; LYMPHOCYTOPENIA; MACULAR EDEMA; MALIGNANT NEOPLASTIC DISEASE; MELANOMA; MULTIPLE SCLEROSIS; NAUSEA; NEOPLASM; PATIENT ATTITUDE; PATIENT MONITORING; PERSONAL EXPERIENCE; POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME; PRACTICE GUIDELINE; RECURRENCE RISK; REVIEW; RHINOPHARYNGITIS; SCREENING; SECOND DEGREE ATRIOVENTRICULAR BLOCK; SIDE EFFECT; SINUSITIS; SKIN CANCER; THORAX PAIN; TORSADE DES POINTES; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; VAGINITIS;

EID: 84935030238     PISSN: None     EISSN: 1177889X     Source Type: Journal    
DOI: 10.2147/PPA.S57354     Document Type: Review

References (78)

1. Novartis Pharmaceuticals. Fingolimod Prescribing Information; 2014. Available from: http://www.pharma.us.novartis.com/product/pi/pdf/gilenya.pdf. Accessed December 8, 2014.
2. European Medicines Agency. European Public Assessment Report (EPAR) for Gilenya; 2014. Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002202/human_med_001433.jsp&mid=WC0b01ac058001d125. Accessed December 8, 2014. [Gilenya: EPAR: Summary report for the public].
3. Kappos L, Radue EW, O’Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;362:387–401. [Pivotal Trial FREEDOMS].
4. Cohen JA, Barkhof F, Comi G, TRANSFORMS Study Group, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362:402–415. [Pivotal Trial FREEDOMS].
5. Hla T, Brinkmann V. Sphingosine 1-phosphate (S1P): physiology and the effects of S1P receptor modulation. Neurology. 2011;76:S3–S8.
6. Brinkmann V. FTY720 (fingolimod) in multiple sclerosis: therapeutic effects in the immune and the central nervous system. Br J Pharmacol. 2009;158:1173–1182.
7. Brinkmann V, Davis MD, Heise CE, et al. The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem. 2002; 277(24):21453–21457.
8. Cohen JA, Chun J. Mechanisms of fingolimod’s efficacy and adverse effects in multiple sclerosis. Ann Neurol. 2011;69(5):759–777.
9. 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(8 suppl 3):S20–S27.
10. Choi JW, Gardell SE, Herr DR, et al. FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor (S1P1) modulation. Proc Natl Acad Sci U S A. 2011;108(2):751–756.
11. Groves A, Kihara Y, Chun J. Fingolimod: direct CNS effects on sphingosine 1-phosphate (S1) receptor modulation and implications in multiple sclerosis therapy. J Neurol Sci. 2013;328(1–2):9–18.
12. Mullershausen F, Zecri F, Cetin C, Billich A, Guerini D, Seuwen K. Persistent signaling induced by FTY720-phosphate is mediated by internalized S1P1 receptors. Nat Chem Biol. 2009;5(6): 428–434.
13. Van Doorn R, Van Horssen J, Verzijl D, et al. Sphingosine 1-phosphate receptors 1 and 3 are upregulated in multiple sclerosis lesions. Glia. 2010;58(12):1465–1476.
14. Scott LJ. Fingolimod: a review of its use in the management of relapsing-remitting multiple sclerosis. CNS Drugs. 2011;8:673–698.
15. Devonshire V, Havrdova E, Radue EW, et al; FREEDOMS study group. Relapse and disability outcomes in patients with multiple sclerosis treated with fingolimod: subgroup analyses of the double-blind, randomized, placebo-controlled FREEDOMS study. Lancet Neurol. 2012;11:420–428.
16. Gasperini C, Ruggieri S. Development of oral agent in the treatment of multiple sclerosis: how the first available oral therapy, fingolimod will change therapeutic paradigm approach. Drug Des Devel Ther. 2012;6:175–186.
17. Gasperini C, Ruggieri S, Mancinelli CR, Pozzilli C. Advances in the treatment of relapsing-remitting multiple sclerosis–critical appraisal of fingolimod. Ther Clin Risk Manag. 2013;9:73–85.
18. Mehling M, Kappos L, Derfuss T. Fingolimod for multiple sclerosis: mechanism of action, clinical outcomes, and future directions. Curr Neurol Neurosci Rep. 2011;11:492–497.
19. Rommer PS, Zettl UK, Kieseier B, et al. Requirement for safety monitoring for approved multiple sclerosis therapies: an overview. Clin Exp Immunol. 2013;175(3):397–407.
20. Ward M, Jones DE, Goldman MD. Overview and safety of fingolimod hydrochloride use in patients with multiple sclerosis. Expert Opin Drug Saf. 2014;13(7):989–998.
21. Kappos L, Cohen J, Collins W, et al. Fingolimod in relapsing multiple sclerosis: an integrated analysis of safety findings. Multiple Sclerosis and Related Disorders. 2014;3(4):494–504.
22. Beran RG, Hegazi Y, Schwartz RS, Cordato DJ. Rebound exacerbation multiple sclerosis following cessation of oral treatment. Mult Scler Relat Disord. 2013;2(3):252–255.
23. Alroughani R, Alroughani R, Almulla A, Lamdhade S, Thussu A. Severe reactivation of multiple sclerosis after discontinuation of fingolimod: an IRIS-associated phenomenon. Mult Scler Relat Disord. 2014;3(6):748.
24. Havla JB, Pellkofer HL, Meinl I, Gerdes LA, Hohfeld R, Kumpfel T. Rebound of disease activity after withdrawal of fingolimod (FTY720) treatment. Arch Neurol. 2012;69(2):262–264.
25. Ghezzi A, Rocca MA, Baroncini D, et al. Disease reactivation after fingolimod discontinuation in two multiple sclerosis patients. J Neurol. 2013;260(1):327–329.
26. Rommer PS, Zettl UK, Kieseier B, et al. Requirement for safety monitoring for approved multiple sclerosis therapies: an overview. Clin Exp Immunol. 2014;175(3):397–407.
27. Singer BA. Initiating oral fingolimod treatment in patients with multiple sclerosis. Ther Adv Neurol Disord. 2013;6(4):269–275.
28. Ontaneda D, Hara-Cleaver C, Rudick RA, Cohen JA, Bermel RA. Early tolerability and safety of fingolimod in clinical practice. J Neurol Sci. 2012;323(1–2):167–172.
29. Thomas K, Ziemssen T. Management of fingolimod in clinical practice. Clin Neurol Neurosurg. 2013;115(suppl 1):S60–S64.
30. Thöne J, Ellrichmann G. Oral available agents in the treatment of relapsing remitting multiple sclerosis: an overview of merits and culprits. Drug Healthc Patient Saf. 2013;5:37–47.
31. Berger JR. Varicella vaccination after fingolimod: a case report. Mult Scler Relat Disord. 2013;2(4):391–394.
32. Jain N, Bhatti MT. Fingolimod-associated macular edema: incidence, detection, and management. Neurology. 2012;78(9):672–680.
33. Coppes O, Gutierrez I, Reder AT, Ksiazek S, Bernard J. Severe early bilateral macular edema following fingolimod therapy. Mult Scler Relat Disord. 2013;2(3):256–258.
34. Gold R, Comi G, Palace J, FIRST Study Investigators, et al. 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(2):267–276.
35. Camm J, Hla T, Bakshi R, Brinkmann V. Cardiac and vascular effects of fingolimod: mechanistic basis and clinical implications. Am Heart J. 2014;168(5):632–644.
36. Horga A, Castrillo J, Montalban X. Fingolimod for relapsing multiple sclerosis; an update. Expert Opin Pharmacother. 2010;11:1183–1196.
37. FDA. Revised Drug Monitoring: US Food and Drug Administration; 2014. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm303192.htm. Accessed December 8, 2014.
38. FDA. First Reported Death on Gilenya: 24hrs Post FDO: US Food and Drug Administration; 2014. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm284240.htm. Accessed December 8, 2014.
39. Thomas K, Schrötter H, Halank M, Ziemssen T. Fingolimod in a patient with heart failure on the background of pulmonary arterial hypertension and coronary artery disease. BMC Neurol. 2014;14:126.
40. Laroni A, Brogi D, Morra VB, et al; EAP Investigators. Safety of the first dose of fingolimod for multiple sclerosis: results of an open-label clinical trial. BMC Neurol. 2014;14:65.
41. Faber H, Fischer H-J, Weber F. Prolonged and symptomatic bradycardia following a single dose of fingolimod. Mult Scler. 2013;19(1):126–128.
42. Singer B, Ross AP, Tobias K. Oral fingolimod for the treatment of patients with relapsing forms of multiple sclerosis. Int J Clin Pract. 2011;65(8):887–895.
43. Calabresi PA, Radue EW, Goodin D, et al. Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomized, placebo-controlled, phase 3 trial. Lancet Neurol. 2014;13(6):545–556.
44. Johnson TA, Shames I, Keezer M, et al. Reconstitution of circulating lymphocyte counts in FTY720-treated MS patients. Clin Immunol. 2010;137(1):15–20.
45. Rosenstiel PV, Gottschalk R, Cappiello L, Zhang Y, Said M, Kappos L. Long-term safety of fingolimod: interim evaluation of data from the longterms trial. Mult Scler Relat Disord. 2014;3(6):752.
46. Hughes B, Cascione M, Freedman MS, et al. First-dose effects of fingolimod after switching from injectable therapies in the randomized, open-label, multicenter, evaluate patient outcomes (EPOC) study in relapsing multiple sclerosis. Mult Scler Relat Disord. 2014;3(5):620–628.
47. Conzett KB, Kolm I, Jelcic I, et al. Melanoma occurring during treatment with fingolimod for multiple sclerosis: a case report. Arch Dermatol. 2011;147(8):991–992.
48. Lorvik KB, Bogen B, Corthay A. Fingolimod blocks immunosurveillance of myeloma and B-cell lymphoma resulting in cancer development in mice. Blood. 2012;119(9):2176–2177.
49. Karlsson G, Francis G, Koren G, et al. Pregnancy outcomes in the clinical development program of fingolimod in multiple sclerosis. Neurology. 2014;82(8):674–680.
50. Jones B. Multiple sclerosis: study reinforces need for contraception in women taking fingolimod. Nat Rev Neurol. 2014;10(3):125.
51. Alwan S, Chambers CD, Armenti VT, Dessa-Sadovnick A. The need for disease-specific prospective pregnancy registry for multiple sclerosis (MS). Mult Scler Relat Disord. 2015;4(1):6–17.
52. Houtchens MK, Kolb CM. Multiple sclerosis and pregnancy: therapeutic considerations. J Neurol. 2013;260(5):1202–1214.
53. Hellmann MA, Lev N, Lotan I, et al. Tumefactive demyelination and a malignant course in an MS patient during and following fingolimod therapy. J Neurol Sci. 2014;344(1–2):193–197.
54. Pilz G, Harrer A, Wipfler P, et al. Tumefactive MS lesions under fingolimod: a case report and literature review. Neurology. 2013;81(19): 1654–1658.
55. Castrop F, Kowarik MC, Albrecht H, et al. Severe multiple sclerosis relapse under fingolimod therapy: incident or coincidence? Neurology. 2012;78(12):928–930.
56. Jander S, Turowski B, Kieseier BC, Hartung H-P. Emerging tumefactive multiple sclerosis after switching therapy from natalizumab to fingolimod. Mult Scler. 2012;18:1650–1652.
57. Daelman L, Maitrot A, Maarouf A, Chaunu MP, Papeix C, Tourbah A. Severe multiple sclerosis reactivation under fingolimod 3 months after natalizumab withdrawal. Mult Scler. 2012;11:1647–1649.
58. Hakiki B, Portaccio E, Giannini M, Razzolini L, Pasto L, Amato MP. Withdrawal of fingolimod treatment for relapsing-remitting multiple sclerosis: report of six cases. Mult Scler. 2012;18(11):1636–1639.
59. Centonze D, Rossi S, Rinaldi F, Gallo P. Severe relapses under fingolimod treatment prescribed after natalizumab. Neurology. 2012; 79(19):2004–2005.
60. Alroughani R, Ahmed S, Al-Hashel J. The risk of short-term relapse in patients switching from natalizumab to fingolimod. Mult Scler Relat Disord. 2014;3(6):748–749.
61. FDA. Brain Infection Case. US Food and Drug Administration; 2014. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm366529.htm. Accessed December 8, 2014.
62. Calic Z, Cappelen-Smith C, Hodgkinson SJ, McDougall A, Cuganesan R, Brew BJ. Treatment of progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome with intravenous immunoglobulin in a patient with multiple sclerosis treated with fingolimod after discontinuation of natalizumab. J Clin Neurosci. 2014;22(3):598–600.
63. Khatri BO, Pelletier J, Kappos L, et al. Effect of prior treatment status and reasons for discontinuation on the efficacy and safety of fingolimod vs interferon B-1a intramuscular: subgroup analyses of the trial assessing injectable interferon vs. fingolimod oral in relapsing-remitting multiple sclerosis (TRANSFORMS). Mult Scler Relat Disord. 2013;3(3):355–363.
64. Khatri B, Barkhof F, Comi G, et al; TRANSFORMS Study Group. Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomized extension of the TRANSFORMS study. Lancet Neurol. 2011;10(6):520–529.
65. Radue EW, O’Connor P, Polman CH, et al; 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(10):1259–1269.
66. Yamout B, Khoury S, Zeineddine M, Hourany R. Efficacy and safety of fingolimod treatment in multiple sclerosis: the clinical experience of the AUBMC Multiple Sclerosis Center in Lebanon. Mult Scler Relat Disord. 2014;3(6):749.
67. Ziemmsen T, Diaz-Lorente M, Abdelkader M, Cornelissen C. PANGAEA: post-authorization Noninterventional German safety Study of Gilenya in relapsing-remitting multiple sclerosis (RRMS) patients: a 24-month interim analysis of a German five-year fingolimod registry study. Mult Scler Relat Disord. 2014;3(6):751.
68. Fazekas F, Bajenaru O, Berger T, et al. How does fingolimod (gilenya(®)) fit in the treatment algorithm for highly active relapsing-remitting multiple sclerosis? Front Neurol. 2013;4:10.
69. Hanson KA, Agashivala N, Wyrwich KW, Raimundo K, Kim E, Brandes DW. Treatment selection and experience in multiple sclerosis: survey of neurologists. Patient Prefer Adherence. 2014;8:415–422.
70. Ontaneda D, Cohn S, Fox RJ. Risk stratification and mitigation in multiple sclerosis. Mult Scler Relat Disord. 2014;3(5):639–649.
71. Fox E, Edwards K, Burch G, et al. Outcomes of switching directly to oral fingolimod from injectable therapies: results of the randomized, open-label, multicenter, evaluate patient outcomes (EPOC) study in relapsing multiple sclerosis. Mult Scler Relat Disord. 2014;3(5): 607–619.
72. Havla J, Tackenberg B, Hellwig K, et al. Fingolimod reduces recurrence of disease activity after natalizumab withdrawal in multiple sclerosis. J Neurol. 2013;260(5):1382–1387.
73. de Seze J, Ongagna JC, Collongues N, et al. Reduction of the washout time between natalizumab and fingolimod. Mult Scler. 2013;19(9):1248.
74. Halpern R, Agarwal S, Borton L, Oneacre K, Lopez-Bresnahan MV. Adherence and persistence among multiple sclerosis patients after one immunomodulatory therapy failure: retrospective claims analysis. Adv Ther. 2011;28(9):761–775.
75. Agashivala N, Wu N, Abouzaid S, et al. Compliance to fingolimod and other disease modifying treatments in multiple sclerosis patients, a retrospective cohort study. BMC Neurol. 2013;13:138.
76. Tan H, Cai Q, Agarwal S, Stephenson JJ, Kamat S. Impact of adherence to disease-modifying therapies on clinical and economic outcomes among patients with multiple sclerosis. Adv Ther. 2011;28(1):51–61.
77. Menzin J, Caon C, Nichols C, White LA, Friedman M, Pill MW. Narrative review of the literature on adherence to disease-modifying therapies among patients with multiple sclerosis. J Manag Care Pharm. 2013;19(1 suppl A):S24–S40.
78. Therapeutic decision making in multiple sclerosis: best practice algorithms for the MS care clinician. Int J MS Care. 2014;16(suppl 6):1–36.