Skip to main content
Top
Published in: CNS Drugs 9/2014

01-09-2014 | Original Research Article

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

Authors: Jasem AL-Hashel, Samar F. Ahmed, Raed Behbehani, Raed Alroughani

Published in: CNS Drugs | Issue 9/2014

Login to get access

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.
Literature
1.
go back to reference 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.PubMed 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.PubMed
2.
go back to reference Lublin FD, Baier M, Cutter G. Effect of relapses on development of residual deficit in multiple sclerosis. Neurology. 2003;61(11):1528–32.PubMedCrossRef Lublin FD, Baier M, Cutter G. Effect of relapses on development of residual deficit in multiple sclerosis. Neurology. 2003;61(11):1528–32.PubMedCrossRef
3.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
4.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
5.
go back to reference 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. 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.
6.
go back to reference 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. 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.
7.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
8.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
9.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
10.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
11.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
12.
go back to reference 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. 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.
13.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
14.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
16.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
17.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
18.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
19.
go back to reference Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33:1444–52.PubMedCrossRef Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33:1444–52.PubMedCrossRef
20.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
22.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
23.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
24.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
25.
go back to reference 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.PubMed 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.PubMed
26.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
27.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
28.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
29.
go back to reference Visser F, Wattjes MP, Pouwels PJ, Linssen WH, van Oosten BW. Tumefactive multiple sclerosis lesions under fingolimod treatment. Neurology. 2012;79(19):2000–3.PubMedCrossRef Visser F, Wattjes MP, Pouwels PJ, Linssen WH, van Oosten BW. Tumefactive multiple sclerosis lesions under fingolimod treatment. Neurology. 2012;79(19):2000–3.PubMedCrossRef
30.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
31.
go back to reference Nealon N. Severe multiple sclerosis relapse on fingolimod. Mult Scler. 2011;17:S53–276.CrossRef Nealon N. Severe multiple sclerosis relapse on fingolimod. Mult Scler. 2011;17:S53–276.CrossRef
32.
go back to reference Castrop F, Kowarik MC, Albrecht H, et al. Severe multiple sclerosis relapse under fingolimod therapy: incident or coincidence? Neurology. 2012;78:928–30.PubMedCrossRef Castrop F, Kowarik MC, Albrecht H, et al. Severe multiple sclerosis relapse under fingolimod therapy: incident or coincidence? Neurology. 2012;78:928–30.PubMedCrossRef
33.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
34.
go back to reference Golden NH, Carlson JL. The pathophysiology of amenorrhea in the adolescent. Ann N Y Acad Sci. 2008;1135:163–78.PubMedCrossRef Golden NH, Carlson JL. The pathophysiology of amenorrhea in the adolescent. Ann N Y Acad Sci. 2008;1135:163–78.PubMedCrossRef
Metadata
Title
Real-World Use of Fingolimod in Patients with Relapsing Remitting Multiple Sclerosis: A Retrospective Study Using the National Multiple Sclerosis Registry in Kuwait
Authors
Jasem AL-Hashel
Samar F. Ahmed
Raed Behbehani
Raed Alroughani
Publication date
01-09-2014
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 9/2014
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.1007/s40263-014-0185-z

Other articles of this Issue 9/2014

CNS Drugs 9/2014 Go to the issue