CNS Drugs

, Volume 28, Issue 9, pp 817–824 | Cite as

Real-World Use of Fingolimod in Patients with Relapsing Remitting Multiple Sclerosis: A Retrospective Study Using the National Multiple Sclerosis Registry in Kuwait

  • Jasem AL-Hashel
  • Samar F. Ahmed
  • Raed Behbehani
  • Raed Alroughani
Original Research Article

Abstract

Background

Fingolimod is an oral sphingosine-1-phosphate–receptor modulator, which has demonstrated efficacy in clinical trials and has recently been approved for multiple sclerosis (MS) treatment in Kuwait. Post-marketing studies are important to demonstrate real-life efficacy and safety.

Objective

The objective of this study was to examine the efficacy and safety of fingolimod treatment in a clinical setting.

Methods

Using the national Kuwait MS registry, relapsing remitting MS patients who had been prescribed fingolimod for ≥6 months were retrospectively identified. Three-monthly clinical evaluations and 6-monthly magnetic resonance imagings (MRIs) were performed. Patient status pre- and post-treatment was compared using chi-square and Student t-tests.

Results

A total of 175 patients were included: 75.4 % female (n = 132); mean age 33.3 ± 9.2 years; mean disease duration 7.2 ± 5.2 years; mean fingolimod use 21.7 ± 9.1 months. Most had used previous disease-modifying therapy (78.9 %; n = 138), mainly interferons (66.9 %; n = 117). Twenty-three patients (11.4 %) discontinued/withdrew fingolimod; of whom eight had relapses. The proportion of relapse-free patients improved significantly (86.3 % vs. 32.6 %; p < 0.001), while the proportion of patients with MRI activity decreased (18.3.6 % vs. 77.7 %; p < 0.001). Mean expanded disability status scale (EDSS) score at the last visit improved when compared with pre-treatment (2.26 ± 1.49 vs. 2.60 ± 1.44; p = 0.03). Forty-three (24.6 %) patients experienced adverse events; headaches and lymphopenia were the most commonly reported adverse events.

Conclusion

Fingolimod treatment was associated with reduced relapse and MRI activity, and an improved EDSS score. Discontinuation/withdrawal rates and adverse events were low. Fingolimod presents a promising treatment for MS in Kuwait.

References

  1. 1.
    Richards RG, Sampson FC, Beard SM, Tappenden P. A review of the natural history and epidemiology of multiple sclerosis: implications for resource allocation and health economic models. Health Technol Assess. 2002;6(10):1–73.PubMedGoogle Scholar
  2. 2.
    Lublin FD, Baier M, Cutter G. Effect of relapses on development of residual deficit in multiple sclerosis. Neurology. 2003;61(11):1528–32.PubMedCrossRefGoogle Scholar
  3. 3.
    Weinshenker BG, Bass B, Rice GP, Noseworthy J, Carriere W, Baskerville J, et al. The natural history of multiple sclerosis: a geographically based study. 2. Predictive value of the early clinical course. Brain. 1989;112(Pt 6):1419–28.PubMedCrossRefGoogle Scholar
  4. 4.
    Jacobs LD, Cookfair DL, Rudick RA, Herndon RM, Richert JR, Salazar AM, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis: the Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol. 1996;39(3):285–94.PubMedCrossRefGoogle Scholar
  5. 5.
    Randomised double-blind placebo-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(9139):1498–504.Google Scholar
  6. 6.
    Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group. Neurology. 1993;43(4):655–61.Google Scholar
  7. 7.
    Johnson KP, Brooks BR, Ford CC, Goodman A, Guarnaccia J, Lisak RP, et al. Sustained clinical benefits of glatiramer acetate in relapsing multiple sclerosis patients observed for 6 years: Copolymer 1 Multiple Sclerosis Study Group. Mult Scler. 2000;6(4):255–66.PubMedCrossRefGoogle Scholar
  8. 8.
    Mehling M, Kappos L, Derfuss T. Fingolimod for multiple sclerosis: mechanism of action, clinical outcomes, and future directions. Curr Neurol Neurosci Rep. 2011;11(5):492–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Kappos L, Radue EW, O’Connor P, Polman C, Hohlfeld R, Calabresi P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;362(5):387–401.PubMedCrossRefGoogle Scholar
  10. 10.
    Cohen JA, Barkhof F, Comi G, Hartung HP, Khatri BO, Montalban X, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):402–15.PubMedCrossRefGoogle Scholar
  11. 11.
    Agashivala N, Wu N, Abouzaid S, Wu Y, Kim E, Boulanger L, et al. Compliance to fingolimod and other disease modifying treatments in multiple sclerosis patients, a retrospective cohort study. BMC Neurol. 2013;13:138.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Agashivala N, Wu N, Abouzaid S, et al. Comparison of compliance to fingolimod and other first-line disease modifying treatment among patients with multiple sclerosis. ACMP 2012 Education Conference, 3–5 October 2012, Cincinnati.Google Scholar
  13. 13.
    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.PubMedCrossRefGoogle Scholar
  14. 14.
    Devonshire V, Lapierre Y, Macdonell R, Ramo-Tello C, Patti F, Fontoura P, et al. The global adherence project (GAP): a multicenter observational study on adherence to disease-modifying therapies in patients with relapsing-remitting multiple sclerosis. Eur J Neurol. 2011;18(1):69–77.PubMedCrossRefGoogle Scholar
  15. 15.
    US Food and Drug Administration. In: Gilenya prescribing information; 2011. http://www.accessdata.fda.gov/drugsatfdadocs/label/2011/022527s002lbl.pdf.
  16. 16.
    Bergvall N, Makin C, Lahoz R, Agashivala N, Pradhan A, Capkun G, et al. Comparative effectiveness of fingolimod versus interferons or glatiramer acetate for relapse rates in multiple sclerosis: a retrospective US claims database analysis. Curr Med Res Opin. 2013;29(12):1647–56.PubMedCrossRefGoogle Scholar
  17. 17.
    Havla J, Tackenberg B, Hellwig K, Meinl I, Krumbholz M, Seitz F, et al. Fingolimod reduces recurrence of disease activity after natalizumab withdrawal in multiple sclerosis. J Neurol. 2013;260(5):1382–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Alroughani R, Ahmed SF, Behbahani R, Khan R, Thussu A, Alexander KJ, et al. Increasing prevalence and incidence rates of multiple sclerosis in Kuwait. Mult Scler. 2014;20(5):543–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33:1444–52.PubMedCrossRefGoogle Scholar
  20. 20.
    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(4):907–11.PubMedCrossRefGoogle Scholar
  21. 21.
  22. 22.
    Agius M, Meng X, Chin P, Grinspan A, Hashmonay R. Fingolimod therapy in early multiple sclerosis: an efficacy analysis of the TRANSFORMS and FREEDOMS studies by time since first symptom. CNS Neurosci Ther. 2014;20(5):446–51.PubMedCrossRefGoogle Scholar
  23. 23.
    Cohen JA, Barkhof F, Comi G, Izquierdo G, Khatri B, Montalban X, et al. Fingolimod versus intramuscular interferon in patient subgroups from TRANSFORMS. J Neurol. 2013;260(8):2023–32.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    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):167–72.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Maciejek Z, Wojcik-Draczkowska H, Wawrzyniak S, Niezgodzinska-Maciejek A. Evaluation of efficacy, safety and tolerability of fingolimod in patients with the relapsing form of multiple sclerosis: 12-month observation. A preliminary report. Neurol Neurochir Pol. 2013;47(2):145–51.PubMedGoogle Scholar
  26. 26.
    Ratchford JN, Costello K, Reich DS, Calabresi PA. Varicella-zoster virus encephalitis and vasculopathy in a patient treated with fingolimod. Neurology. 2012;79(19):2002–4.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Hanson KA, Agashivala N, Stringer SM, Balantac Z, Brandes DW. A cross-sectional survey of patient satisfaction and subjective experiences of treatment with fingolimod. Patient Prefer Adherence. 2013;7:309–18.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Yamout B, Alroughani R, Al-Jumah M, Khoury S, Abouzeid N, Dahdaleh M, et al. Consensus guidelines for the diagnosis and treatment of multiple sclerosis. Curr Med Res Opin. 2013;29(6):611–21.PubMedCrossRefGoogle Scholar
  29. 29.
    Visser F, Wattjes MP, Pouwels PJ, Linssen WH, van Oosten BW. Tumefactive multiple sclerosis lesions under fingolimod treatment. Neurology. 2012;79(19):2000–3.PubMedCrossRefGoogle Scholar
  30. 30.
    Pilz G, Harrer A, Wipfler P, Oppermann K, Sellner J, Fazekas F, Trinka E, Kraus J. Tumefactive MS lesions under fingolimod: a case report and literature review. Neurology. 2013;81(19):1654–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Nealon N. Severe multiple sclerosis relapse on fingolimod. Mult Scler. 2011;17:S53–276.CrossRefGoogle Scholar
  32. 32.
    Castrop F, Kowarik MC, Albrecht H, et al. Severe multiple sclerosis relapse under fingolimod therapy: incident or coincidence? Neurology. 2012;78:928–30.PubMedCrossRefGoogle Scholar
  33. 33.
    Brinkmann V. Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacology. Pharmacol Ther. 2007;115(1):84–105.PubMedCrossRefGoogle Scholar
  34. 34.
    Golden NH, Carlson JL. The pathophysiology of amenorrhea in the adolescent. Ann N Y Acad Sci. 2008;1135:163–78.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Jasem AL-Hashel
    • 1
    • 2
  • Samar F. Ahmed
    • 1
    • 3
  • Raed Behbehani
    • 4
    • 5
  • Raed Alroughani
    • 5
    • 6
  1. 1.Department of NeurologyIbn Sina HospitalSafatKuwait
  2. 2.Faculty of MedicineKuwait UniversitySafatKuwait
  3. 3.Department of Neurology and PsychiatryMinia UniversityMiniaEgypt
  4. 4.Department of OphthalmologyAl-Bahar Eye CenterKuwait CityKuwait
  5. 5.Neurology ClinicDasman Diabetes InstituteDasmanKuwait
  6. 6.Division of Neurology, Department of MedicineAmiri HospitalSharqKuwait

Personalised recommendations